Objectives. Periprosthetic femoral fractures (PFFs) have a higher incidence with cementless stems. The highest incidence among various cementless stem types was observed with double-wedged stems. Short stems have been introduced as a bone-preserving alternative with a higher incidence of PFF in some studies. The purpose of this study was a direct load-to-failure comparison of a double-wedged cementless stem and a short cementless stem in a cadaveric fracture model. Methods. Eight hips from four human cadaveric specimens (age mean 76 years (60 to 89)) and eight fourth-generation composite femurs were used. None of the cadaveric specimens had compromised quality (mean T value 0.4 (-1.0 to 5.7)). Each specimen from a pair randomly received either a double-wedged stem or a short stem. A materials testing machine was used for lateral load-to-failure test of up to a maximal load of 5000 N. Results. Mean load at failure of the double-wedged stem was 2540 N (1845 to 2995) and 1867 N (1135 to 2345) for the short stem (p < 0.001). All specimens showed the same fracture pattern, consistent with a Vancouver B2 fracture. The double-wedged stem was able to sustain a higher load than its short-stemmed counterpart in all cases. Failure force was not correlated to the bone mineral density (p = 0.718). Conclusion. Short stems have a significantly lower primary load at failure compared with double-wedged stems in both cadaveric and composite specimens. Surgeons should consider this biomechanical property when deciding on the use of short femoral stem. Cite this article: A. Klasan, M. Bäumlein, P. Dworschak, C. Bliemel, T. Neri, M. D. Schofer, T. J. Heyse. Short stems have lower load at failure than double-wedged stems in a cadaveric cementless fracture model. Bone Joint Res 2019;8:489–494. DOI: 10.1302/2046-3758.810.BJR-2019-0051.R1

Aims. The Exeter V40 cemented femoral stem was first introduced in 2000. The largest single-centre analysis of this implant to date was published in 2018 by Westerman et al. Excellent results were reported at a minimum of ten years for the first 540 cases performed at the designer centre in the Exeter NHS Trust, with stem survivorship of 96.8%. The aim of this current study is to report long-term outcomes and survivorship for the Exeter V40 stem in a non-designer centre. Methods. All patients undergoing primary total hip arthroplasty using the Exeter V40 femoral stem between 1 January 2005 and 31 January 2010 were eligible for inclusion. Data were collected prospectively, with routine follow-up at six to 12 months, two years, five years, and ten years. Functional outcomes were assessed using Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores. Outcome measures included data on all components in situ beyond ten years, death occurring within ten years with components in situ, and all-cause revision surgery. Results. A total of 829 stems in 745 patients were included in the dataset; 155 patients (20.8%) died within ten years, and of the remaining 664 stems, 648 stems (97.6%) remained in situ beyond ten years. For the 21 patients (2.5%) undergoing revision surgery, 16 femoral stems (1.9%) were revised and 18 acetabular components (2.2%) were revised. Indications for revision in order of decreasing frequency were infection (n = 6), pain (n = 6), aseptic component loosening (n = 3), periprosthetic fracture (n = 3), recurrent dislocation (n = 2), and noise production (ceramic-on-ceramic squeak) (n = 1). One patient was revised for aseptic stem loosening. The mean preoperative WOMAC score was 61 (SD 15.9) with a mean postoperative score of 20.4 (SD 19.3) (n = 732; 88.3%). Conclusion. The Exeter V40 cemented femoral stem demonstrates excellent functional outcomes and survival when used in a high volume non-designer centre. Outcomes are comparable to those of its serially validated predecessor, the Exeter Universal stem. Cite this article: Bone Jt Open 2020;1-12:743–748

Aims. The aim of this study was to compare the design of the generic OptiStem XTR femoral stem with the established Exeter femoral stem. Materials and Methods. We obtained five boxed, as manufactured, implants of both designs at random (ten in total). Two examiners were blinded to the implant design and independently measured the mass, volume, trunnion surface topography, trunnion roughness, trunnion cone angle, Caput-Collum-Diaphyseal (CCD) angle, femoral offset, stem length, neck length, and the width and roughness of the polished stem shaft using peer-reviewed methods. We then compared the stems using these parameters. Results. We found that the OptiStems were lighter (p < 0.001), had a rougher trunnion surface (p <  0.001) with a greater spacing and depth of the machined threads (p < 0.001), had greater trunnion cone angles (p = 0.007), and a smaller radius at the top of the trunnion (p = 0.007). There was no difference in stem volume (p = 0.643), CCD angle (p = 0.788), offset (p = 0.993), neck length (p = 0.344), stem length (p = 0.808), shaft width (p = 0.058 to 0.720) or roughness of the polished surface (p = 0.536). Conclusion. This preliminary investigation found that whilst there were similarities between the two designs, the generic OptiStem is different to the branded Exeter design. Cite this article: Bone Joint J 2017;99-B:310–16

This was a retrospective analysis of the medium- to long-term results of 46 TC3 Sigma revision total knee replacements using long uncemented stems in press-fit mode. Clinical and radiological analysis took place pre-operatively, at two years post-operatively, and at a mean follow-up of 8.5 years (4 to 12). The mean pre-operative International Knee Society (IKS) clinical score was 42 points (0 to 74), improving to 83.7 (52 to 100) by the final follow-up. The mean IKS score for function improved from 34.3 points (0 to 80) to 64.2 (15 to 100) at the final follow-up. At the final follow-up 30 knees (65.2%) had an excellent result, seven (15.2%) a good result, one (2.2%) a medium and eight (17.4%) a poor result. There were two failures, one with anteroposterior instability and one with aseptic loosening. The TC3 revision knee system, when used with press-fit for long intramedullary stems and cemented femoral and tibial components, in both septic and aseptic revisions, results in a satisfactory clinical and radiological outcome, and has a good medium- to long-term survival rate

Aims. Refobacin Bone Cement R and Palacos R + G bone cement were introduced to replace the original cement Refobacin Palacos R in 2005. Both cements were assumed to behave in a biomechanically similar fashion to the original cement. The primary aim of this study was to compare the migration of a polished triple-tapered femoral stem fixed with either Refobacin Bone Cement R or Palacos R + G bone cement. Repeated radiostereometric analysis was used to measure migration of the femoral head centre. The secondary aims were evaluation of cement mantle, stem positioning, and patient-reported outcome measures. Methods. Overall, 75 patients were included in the study and 71 were available at two years postoperatively. Prior to surgery, they were randomized to one of the three combinations studied: Palacos cement with use of the Optivac mixing system, Refobacin with use of the Optivac system, and Refobacin with use of the Optipac system. Cemented MS30 stems and cemented Exceed acetabular components were used in all hips. Postoperative radiographs were used to assess the quality of the cement mantle according to Barrack et al, and the position and migration of the femoral stem. Harris Hip Score, Oxford Hip Score, Forgotten Joint Score, and University of California, Los Angeles Activity Scale were collected. Results. Median distal migration (y-axis) at two years for the Refobacin-Optivac system was -0.79 mm (-2.01 to -0.09), for the Refobacin-Optipac system was -0.75 mm (-2.16 to 0.20), and for the Palacos-Optivac system was -1.01 mm (-4.31 to -0.29). No statistically significant differences were found between the groups. Secondary outcomes did not differ statistically between the groups at the two-year follow-up. Conclusion. At two years, we found no significant differences in distal migration or clinical outcomes between the three groups. Our data indicate that Refobacin Bone Cement R and Palacos R + G are comparable in terms of stable fixation and early clinical outcomes. Cite this article: Bone Joint J 2024;106-B(5):435–441

Aims. The aim of this study was to evaluate the suitability of the tapered cone stem in total hip arthroplasty (THA) in patients with excessive femoral anteversion and after femoral osteotomy. Methods. We included patients who underwent THA using Wagner Cone due to proximal femur anatomical abnormalities between August 2014 and January 2019 at a single institution. We investigated implant survival time using the endpoint of dislocation and revision, and compared the prevalence of prosthetic impingements between the Wagner Cone, a tapered cone stem, and the Taperloc, a tapered wedge stem, through simulation. We also collected Oxford Hip Score (OHS), visual analogue scale (VAS) satisfaction, and VAS pain by postal survey in August 2023 and explored variables associated with those scores. Results. Of the 58 patients (62 hips), two (two hips) presented with dislocation or reoperation, and Kaplan-Meier analysis indicated a five-year survival rate of 96.7% (95% CI 92.4 to 100). Mean stem anteversion was 35.2° (SD 18.2°) for the Taperloc stem and 29.8° (SD 7.9°) for the Wagner Cone stem; mean reduction from Taperloc to Wagner Cone was 5.4° (SD 18.8°). Overall, 55 hips (52 patients) were simulated, and the prevalence of prosthetic impingement was lower for the Wagner Cone (5.5%, 3/55) compared with the Taperloc (20.0%, 11/55) stem, with an odds ratio of 0.20 (p = 0.038). Among the 33 respondents to the postal survey (36 hips), the mean scores were VAS pain 10.9, VAS satisfaction 86.9, and OHS 44.7. A multivariable analysis revealed that reduction of stem anteversion from Taperloc to Wagner Cone was more favourable for VAS pain (p = 0.029) and VAS satisfaction (p = 0.002). Conclusion. The mid-term survival rate for THA using the Wagner Cone stem was high, which may be supported by a reduction in prosthetic impingement. The reduction in excessive stem anteversion by using a tapered cone stem was associated with reduced pain and increased patient satisfaction. Cite this article: Bone Jt Open 2024;5(10):858–867

Aims. The Exeter short stem was designed for patients with Dorr type A femora and short-term results are promising. The aim of this study was to evaluate the minimum five-year stem migration pattern of Exeter short stems in comparison with Exeter standard stems. Methods. In this case-control study, 25 patients (22 female) at mean age of 78 years (70 to 89) received cemented Exeter short stem (case group). Cases were selected based on Dorr type A femora and matched first by Dorr type A and then age to a control cohort of 21 patients (11 female) at mean age of 74 years (70 to 89) who received with cemented Exeter standard stems (control group). Preoperatively, all patients had primary hip osteoarthritis and no osteoporosis as confirmed by dual X-ray absorptiometry scanning. Patients were followed with radiostereometry for evaluation of stem migration (primary endpoint), evaluation of cement quality, and Oxford Hip Score. Measurements were taken preoperatively, and at three, 12, and 24 months and a minimum five-year follow-up. Results. At three months, subsidence of the short stem -0.87 mm (95% confidence interval (CI) -1.07 to -0.67) was lower compared to the standard stem -1.59 mm (95% CI -1.82 to -1.36; p < 0.001). Both stems continued a similar pattern of subsidence until five-year follow-up. At five-year follow-up, the short stem had subsided mean -1.67 mm (95% CI -1.98 to -1.36) compared to mean -2.67 mm (95% CI -3.03 to -2.32) for the standard stem (p < 0.001). Subsidence was not influenced by preoperative bone quality (osteopenia vs normal) or cement mantle thickness. Conclusion. The standard Exeter stem had more early subsidence compared with the short Exeter stem in patients with Dorr type A femora, but thereafter a similar migration pattern of subsidence until minimum five years follow-up. Both the standard and the short Exeter stems subside. The standard stem subsides more compared to the short stem in Dorr type A femurs. Subsidence of the Exeter stems was not affected by cement mantle thickness. Cite this article: Bone Jt Open 2023;4(7):507–515

Aims. Mesenchymal stem cells (MSCs) are usually cultured in a normoxic atmosphere (21%) in vitro, while the oxygen concentrations in human tissues and organs are 1% to 10% when the cells are transplanted in vivo. However, the impact of hypoxia on MSCs has not been deeply studied, especially its translational application. Methods. In the present study, we investigated the characterizations of human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) in hypoxic (1%) and normoxic (21%) atmospheres with a long-term culture from primary to 30 generations, respectively. The comparison between both atmospheres systematically analyzed the biological functions of MSCs, mainly including stemness maintenance, immune regulation, and resistance to chondrocyte apoptosis, and studied their joint function and anti-inflammatory effects in osteoarthritis (OA) rats constructed by collagenase II. Results. We observed that long-term hypoxic culture surpassed normoxic atmosphere during hUC-MSCs culture in respect of promoting proliferation, anti-tumorigenicity, maintaining normal karyotype and stemness, inhibiting senescence, and improving immunoregulatory function and the role of anti-apoptosis in chondrocytes. Furthermore, we demonstrated that the transplantation of long-term hypoxic hUC-MSCs (Hy-MSCs) had a better therapeutic effect on OA rats compared with the hUC-MSCs cultured in the normoxic atmosphere (No-MSCs) in terms of the improved function and swelling recovery in the joints, and substantially inhibited the secretion of pro-inflammatory factors, which effectively alleviated cartilage damage by reducing the expression of matrix metallopeptidase 13 (MMP-13). Conclusion. Our results demonstrate that Hy-MSCs possess immense potential for clinical applications via promoting stemness maintenance and enhancing immunoregulatory function. Cite this article: Bone Joint Res 2024;13(12):763–777

Aims. The aim of this study was to compare the mid-term patient-reported outcome, bone remodelling, and migration of a short stem (Collum Femoris Preserving; CFP) with a conventional uncemented stem (Corail). Methods. Of 81 patients who were initially enrolled, 71 were available at five years’ follow-up. The outcomes at two years have previously been reported. The primary outcome measure was the clinical result assessed using the Oxford Hip Score (OHS). Secondary outcomes were the migration of the stem, measured using radiostereometric analysis (RSA), change of bone mineral density (BMD) around the stem, the development of radiolucent lines, and additional patient-reported outcome measures (PROMs). Results. There were no statistically significant differences between the groups regarding PROMs (median OHS (CFP 45 (interquartile range (IQR) 35 to 48); Corail 45 (IQR 40 to 48); p = 0.568). RSA showed stable stems in both groups, with little or no further subsidence between two and five years. Resorption of the femoral neck was evident in nine patients in the CFP group and in none of the 15 Corail stems with a collar that could be studied. Dual X-ray absorbiometry showed a significantly higher loss of BMD in the proximal Gruen zones in the CFP group (mean changes in BMD: Gruen zone 1, CFP -9.5 (95% confidence interval (CI) -14.8 to -4.2), Corail 1.0 (95% CI 3.4 to 5.4); Gruen zone 7, CFP -23.0 (95% CI -29.4 to -16.6), Corail -7.2 (95% CI -15.9 to 1.4). Two CFP stems were revised before two years’ follow-up due to loosening, and one Corail stem was revised after two years due to chronic infection. Conclusion. The CFP stem has a similar clinical outcome and subsidence pattern when compared with the Corail stem. More pronounced proximal stress-shielding was seen with the CFP stem, suggesting diaphyseal fixation, and questioning its femoral neck-sparing properties in the long term. Cite this article: Bone Joint J 2022;104-B(5):581–588

Aims. The aim of this study was to evaluate the differences in revision and complication rates, functional outcomes, and radiological outcomes between cemented and press-fit humeral stems in primary anatomical total shoulder arthroplasty (TSA). Materials and Methods. A comprehensive systematic review and meta-analysis was conducted searching for studies that included patients who underwent primary anatomical TSA for primary osteoarthritis or rheumatoid arthritis. Results. There was a total of 36 studies with 927 cemented humeral stems and 1555 press-fit stems. The revision rate was 5.4% (95% confidence interval (CI) 3.9 to 7.4) at a mean of 89 months for cemented stems, and 2.4% (95% CI 1.1 to 4.7) at a mean of 40 months for press-fit stems. A priori subgroup analysis to control for follow-up periods demonstrated similar revision rates: 2.3% (95% CI 1.1 to 4.7) for cemented stems versus 1.8% (95% CI 1.4 to 2.9) for press-fit stems. Exploratory meta-regression found that longer follow-up was a moderating variable for revision (p = 0.003). Conclusion. Cement fixation had similar revision rates when compared to press-fit stems at short- to midterm follow-up. Rotator cuff pathology was a prevalent complication in both groups but is likely not related to fixation type. Overall, with comparable revision rates, possible easier revision, and decreased operative time, humeral press-fit fixation may be an optimal choice for primary anatomical TSA in patients with sufficient bone stock. Cite this article: Bone Joint J 2019;101-B:1107–1114

Aims. United Classification System (UCS) B2 and B3 periprosthetic fractures in total hip arthroplasties (THAs) have been commonly managed with modular tapered stems. No study has evaluated the use of monoblock fluted tapered titanium stems for this indication. This study aimed to evaluate the effects of a monoblock stems on implant survivorship, postoperative outcomes, radiological outcomes, and osseointegration following treatment of THA UCS B2 and B3 periprosthetic fractures. Methods. A retrospective review was conducted of all patients who underwent revision THA (rTHA) for periprosthetic UCS B2 and B3 periprosthetic fracture who received a single design monoblock fluted tapered titanium stem at two large, tertiary care, academic hospitals. A total of 72 patients met inclusion and exclusion criteria (68 UCS B2, and four UCS B3 fractures). Primary outcomes of interest were radiological stem subsidence (> 5 mm), radiological osseointegration, and fracture union. Sub-analysis was also done for 46 patients with minimum one-year follow-up. Results. For the total cohort, stem osseointegration, fracture union, and stem subsidence were 98.6%, 98.6%, and 6.9%, respectively, at latest follow-up (mean follow-up 27.0 months (SD 22.4)). For patients with minimum one-year of follow-up, stem osseointegration, fracture union, and stem subsidence were 97.8%, 97.8%, and 6.5%, respectively. Conclusion. Monoblock fluted stems can be an acceptable modality for the management of UCS B2 periprosthetic fractures in rTHAs due to high rates of stem osseointegration and survival, and the low rates of stem subsidence, and revision. Further research on the use of this stem for UCS B3 periprosthetic fractures is warranted to determine if the same conclusion can be made for this fracture pattern. Cite this article: Bone Jt Open 2023;4(8):551–558

Aims. Despite higher rates of revision after total hip arthroplasty (THA) being reported for uncemented stems in patients aged > 75 years, they are frequently used in this age group. Increased mortality after cemented fixation is often used as a justification, but recent data do not confirm this association. The aim of this study was to investigate the influence of the design of the stem and the type of fixation on the rate of revision and immediate postoperative mortality, focusing on the age and sex of the patients. Methods. A total of 333,144 patients with primary osteoarthritis (OA) of the hip who underwent elective THA between November 2012 and September 2022, using uncemented acetabular components without reconstruction shells, from the German arthroplasty registry were included in the study. The revision rates three years postoperatively for four types of stem (uncemented, uncemented with collar, uncemented short, and cemented) were compared within four age groups: < 60 years (Young), between 61 and 70 years (Mid-I), between 71 and 80 years (Mid-II), and aged > 80 years (Old). A noninferiority analysis was performed on the most frequently used designs of stem. Results. The design of the stem was found to have no significant influence on the rate of revision for either sex in the Young group. Uncemented collared stems had a significantly lower rate of revision compared with the other types of stem for females in the Mid-I group. There was a significantly higher rate of revision for uncemented stems in females in the Mid-II group compared with all other types of stem, while in males the rate for uncemented stems was only significantly higher than the rate for cemented stems. Cemented stems had a significantly lower revision rate compared with uncemented and short stems for both sexes in the Old cohort, as did females with collared stems. The rate of immediate postoperative mortality was similar for all types of stem in the Old age group, as were the American Society of Anesthesiologists grades. Conclusion. In patients aged > 80 years, uncemented and short stems had significantly higher revision rates compared with cemented and collared stems, especially in females. The design of the stem and type of fixation have to be analyzed in more detail than only considering cemented and uncemented fixation, in order to further improve the success of THA. Cite this article: Bone Joint J 2024;106-B(3 Supple A):130–136

Polished taper-slip (PTS) cemented stems have an excellent clinical track record and are the most common stem type used in primary total hip arthroplasty (THA) in the UK. Due to low rates of aseptic loosening, they have largely replaced more traditional composite beam (CB) cemented stems. However, there is now emerging evidence from multiple joint registries that PTS stems are associated with higher rates of postoperative periprosthetic femoral fracture (PFF) compared to their CB stem counterparts. The risk of both intraoperative and postoperative PFF remains greater with uncemented stems compared to either of these cemented stem subtypes. PFF continues to be a devastating complication following primary THA and is associated with high complication and mortality rates. Recent efforts have focused on identifying implant-related risk factors for PFF in order to guide preventative strategies, and therefore the purpose of this article is to present the current evidence on the effect of cemented femoral stem design on the risk of PFF. Cite this article: Bone Joint J 2024;106-B(1):11–15

Aims. The Exeter V40 femoral stem is the most implanted stem in the National Joint Registry (NJR) for primary total hip arthroplasty (THA). In 2004, the 44/00/125 stem was released for use in ‘cement-in-cement’ revision cases. It has, however, been used ‘off-label’ as a primary stem when patient anatomy requires a smaller stem with a 44 mm offset. We aimed to investigate survival of this implant in comparison to others in the range when used in primary THAs recorded in the NJR. Methods. We analyzed 328,737 primary THAs using the Exeter V40 stem, comprising 34.3% of the 958,869 from the start of the NJR to December 2018. Our exposure was the stem, and the outcome was all-cause construct revision. We stratified analyses into four groups: constructs using the 44/00/125 stem, those using the 44/0/150 stem, those including a 35.5/125 stem, and constructs using any other Exeter V40 stem. Results. In all 328,737 THAs using an Exeter V40 stem, the revision estimate was 2.8% (95% confidence interval (CI) 2.7 to 2.8). The 44/00/125 stem was implanted in 2,158 primary THAs, and the ten-year revision estimate was 4.9% (95% CI 3.6 to 6.8). Controlling for age, sex, year of operation, indication, and American Society of Anesthesiologists grade demonstrated an increased overall hazard of revision for constructs using the 44/00/125 stem compared to constructs using other Exeter V40 femoral stems (hazard ratio 1.8 (95% CI 1.4 to 2.3)). Conclusion. Although the revision estimate is within the National Institute for Health and Care Excellence ten-year benchmark, survivorship of constructs using the 44/00/125 stem appears to be lower than the rest of the range. Adjusted analyses will not take into account ‘confounding by indication’, e.g. patients with complex anatomy who may have a higher risk of revision. Surgeons and patients should be reassured but be aware of the observed increased revision estimate, and only use this stem when other implants are not suitable. Cite this article: Bone Joint J 2023;105-B(5):504–510

The purpose of this prospective study was to evaluate the long-term clinical and radiological outcomes of revision of the femoral component of a total hip replacement using impaction bone grafting. Femoral revision with an impacted allograft was performed on 29 patients (31 hips). In all, 21 hips (68%) had grade III or IV femoral defects according to the Endo-Klinik classification. A total of 11 patients (12 hips) died before the ten-year follow-up period. Of the remaining patients, 18 patients (19 hips) were followed for 10 to 15 years; three further patients died during this time. None of the 31 stems underwent further revision of their stem. However, four stems showed extensive subsidence (> 15 mm). One of these patients had a femoral fracture that required fixation. Three other patients had a femoral fracture, two of which required fixation and the other was treated conservatively. Patients with a femoral fracture and/or severe subsidence had significantly more grade IV defects (six of seven hips; p = 0.004). One patient needed a closed reduction for dislocation. Impaction allografting in revision hip surgery gives good long-term results for femora with grades I, II and III Endo-Klinik-classified defects. Extensive subsidence and femoral fractures were seen mainly in patients with grade IV damaged femora

Objectives. Favourable results for collarless polished tapered stems have been reported, and cement creep due to taper slip may be a contributing factor. However, the ideal cement thickness around polished stems remains unknown. We investigated the influence of cement thickness on stem subsidence and cement creep. Methods. We cemented six collarless polished tapered (CPT) stems (two stems each of small, medium and large sizes) into composite femurs that had been reamed with a large CPT rasp to achieve various thicknesses of the cement mantle. Two or three tantalum balls were implanted in the proximal cement in each femur. A cyclic loading test was then performed for each stem. The migration of the balls was measured three-dimensionally, using a micro-computed tomography (CT) scanner, before and after loading. A digital displacement gauge was positioned at the stem shoulder, and stem subsidence was measured continuously by the gauge. Final stem subsidence was measured at the balls at the end of each stem. Results. A strong positive correlation was observed between mean cement thickness and stem subsidence in the CT slices on the balls. In the small stems, the balls moved downward to almost the same extent as the stem. There was a significant negative correlation between cement thickness and the horizontal:downward ratio of ball movement. Conclusion. Collarless polished tapered stems with thicker cement mantles resulted in greater subsidence of both stem and cement. This suggests that excessive thickness of the cement mantle may interfere with effective radial cement creep. Cite this article: E. Takahashi, A. Kaneuji, R. Tsuda, Y. Numata, T. Ichiseki, K. Fukui, N. Kawahara. The influence of cement thickness on stem subsidence and cement creep in a collarless polished tapered stem: When are thick cement mantles detrimental? Bone Joint Res 2017;6:–357. DOI: 10.1302/2046-3758.65.BJR-2017-0028.R1

Aims. The aim of this large registry-based study was to compare mid-term survival rates of cemented femoral stems of different designs used in hemiarthroplasty for a fracture of the femoral neck. Patients and Methods. From the Norwegian Hip Fracture Register (NHFR), 20 532 primary cemented bipolar hemiarthroplasties, which were undertaken in patients aged > 70 years with a femoral neck fracture between 2005 and 2016, were included. Polished tapered stems (n = 12 065) (Exeter and CPT), straight stems (n = 5545) (Charnley, Charnley Modular, and Spectron EF), and anatomical stems (n = 2922) (Lubinus SP2) were included. The survival of the implant with any reoperation as the endpoint was calculated using the Kaplan–Meier method and hazard ratios (HRs), and the different indications for reoperation were calculated using Cox regression analysis. Results. The one-year survival was 96.0% (95% confidence interval (CI) 95.6 to 96.4) for the Exeter stem, 97.0% (95% CI 96.4 to 97.6) for the Lubinus SP2 stem, 97.6% (95% CI 97.0 to 98.2) for the Charnley stem, 98.1% (95% CI 97.3 to 98.9) for the Spectron EF stem, and 96.4% (95% CI 95.6 to 97.2) for the Charnley Modular stem, respectively. The hazard ratio for reoperation after one year was lower for Lubinus SP2 (HR 0.77, 95% CI 0.60 to 0.97), Charnley (HR 0.64, 95% CI 0.48 to 0.86), and Spectron EF stems (HR 0.44, 95% CI 0.29 to 0.67) compared with the Exeter stem. Reoperation for periprosthetic fracture occurred almost exclusively after the use of polished tapered stems. Conclusion. We were able to confirm that implant survival after cemented hemiarthroplasty for a hip fracture is high. Differences in rates of reoperation seem to favour anatomical and straight stems compared with polished tapered stems, which had a higher risk of periprosthetic fracture

Aims. The risk of mechanical failure of modular revision hip stems is frequently mentioned in the literature, but little is currently known about the actual clinical failure rates of this type of prosthesis. The current retrospective long-term analysis examines the distal and modular failure patterns of the Prevision hip stem from 18 years of clinical use. A design improvement of the modular taper was introduced in 2008, and the data could also be used to compare the original and the current design of the modular connection. Methods. We performed an analysis of the Prevision modular hip stem using the manufacturer’s vigilance database and investigated different mechanical failure patterns of the hip stem from January 2004 to December 2022. Results. Two mechanical failure patterns were identified: fractures in the area of the distal fluted profile (distal stem fracture) and failure of the modular taper (modular fracture). A failure rate of 0.07% was observed for distal stem fracture, and modular fracture rates of 1.74% for the original and 0.013% for the current taper design. Conclusion. A low risk of mechanical failure for both fracture types was observed compared to other known complications in revision hip arthroplasty. In addition, the data show that a design change did significantly reduce the risk of a modular fracture. Cite this article: Bone Joint J 2024;106-B(2):151–157

Aims. The aim of this study was to identify the optimal lip position for total hip arthroplasties (THAs) using a lipped liner. There is a lack of consensus on the optimal position, with substantial variability in surgeon practice. Methods. A model of a THA was developed using a 20° lipped liner. Kinematic analyses included a physiological range of motion (ROM) analysis and a provocative dislocation manoeuvre analysis. ROM prior to impingement was calculated and, in impingement scenarios, the travel distance prior to dislocation was assessed. The combinations analyzed included nine cup positions (inclination 30-40-50°, anteversion 5-15-25°), three stem positions (anteversion 0-15-30°), and five lip orientations (right hip 7 to 11 o’clock). Results. The position of the lip changes the ROM prior to impingement, with certain combinations leading to impingement within the physiological ROM. Inferior lip positions (7 to 8 o’clock) performed best with cup inclinations of 30° and 40°. Superior lip positions performed best with cup inclination of 50°. When impingement occurs in the plane of the lip, the lip increases the travel distance prior to dislocation. Inferior lip positions led to the largest increase in jump distance in a posterior dislocation provocation manoeuvre. Conclusion. The lip orientation that provides optimal physiological ROM depends on the orientation of the cup and stem. For a THA with stem anteversion 15°, cup inclination 40°, and cup anteversion 15°, the optimal lip position was posterior-inferior (8 o’clock). Maximizing jump distance prior to dislocation while preventing impingement in the opposite direction is possible with appropriate lip positioning. Cite this article: Bone Joint Res 2023;12(9):571–579

The Unified Classification System (UCS), or Vancouver system, is a validated and widely used classification system to guide the management of periprosthetic femoral fractures. It suggests that well-fixed stems (type B1) can be treated with fixation but that loose stems (types B2 and B3) should be revised. Determining whether a stem is loose can be difficult and some authors have questioned how to apply this classification system to polished taper slip stems which are, by definition, loose within their cement mantle. Recent evidence has challenged the common perception that revision surgery is preferable to fixation surgery for UCS-B periprosthetic fractures around cemented polished taper slip stems. Indications for fixation include an anatomically reducible fracture and cement mantle, a well-fixed femoral bone-cement interface, and a well-functioning acetabular component. However, not all type B fractures can or should be managed with fixation due to the risk of early failure. This annotation details specific fracture patterns that should not be managed with fixation alone. Cite this article: Bone Joint J 2023;105-B(5):481–486

Aims. Endoprosthetic reconstruction following distal femur tumour resection has been widely advocated. In this paper, we present the design of an uncemented endoprosthesis system featuring a short, curved stem, with the goal of enhancing long-term survivorship and functional outcomes. Methods. This study involved patients who underwent implantation of an uncemented distal femoral endoprosthesis with a short and curved stem between 2014 and 2019. Functional outcomes were assessed using the 1993 version of the Musculoskeletal Tumour Society (MSTS-93) score. Additionally, we quantified five types of complications and assessed osseointegration radiologically. The survivorship of the endoprosthesis was evaluated according to two endpoints. A total of 134 patients with a median age of 26 years (IQR 16 to 41) were included in our study. The median follow-up time was 61 months (IQR 56 to 76), and the median functional MSTS-93 was 83% (IQR 73 to 91) postoperatively. Results. Overall, 21 patients (16%) encountered complications, and the rate of aseptic loosening was 7% (9/134). The survival rate up to 8.5 years was 93% for aseptic loosening as the endpoint, and 88% for any reason as the endpoint, retrospectively. Conclusion. The use of an uncemented distal femoral endoprosthesis with a short, curved stem demonstrated a low incidence of aseptic loosening and achieved long-term survivorship of up to nine years. Meanwhile, aseptic loosening typically occurs in the early stage postoperatively. Cite this article: Bone Joint J 2024;106-B(9):1000–1007

Aims. In computer simulations, the shape of the range of motion (ROM) of a stem with a cylindrical neck design will be a perfect cone. However, many modern stems have rectangular/oval-shaped necks. We hypothesized that the rectangular/oval stem neck will affect the shape of the ROM and the prosthetic impingement. Methods. Total hip arthroplasty (THA) motion while standing and sitting was simulated using a MATLAB model (one stem with a cylindrical neck and one stem with a rectangular neck). The primary predictor was the geometry of the neck (cylindrical vs rectangular) and the main outcome was the shape of ROM based on the prosthetic impingement between the neck and the liner. The secondary outcome was the difference in the ROM provided by each neck geometry and the effect of the pelvic tilt on this ROM. Multiple regression was used to analyze the data. Results. The stem with a rectangular neck has increased internal and external rotation with a quatrefoil cross-section compared to a cone in a cylindrical neck. Modification of the cup orientation and pelvic tilt affected the direction of projection of the cone or quatrefoil shape. The mean increase in internal rotation with a rectangular neck was 3.4° (0° to 7.9°; p < 0.001); for external rotation, it was 2.8° (0.5° to 7.8°; p < 0.001). Conclusion. Our study shows the importance of attention to femoral implant design for the assessment of prosthetic impingement. Any universal mathematical model or computer simulation that ignores each stem’s unique neck geometry will provide inaccurate predictions of prosthetic impingement. Cite this article: Bone Joint Res 2021;10(12):780–789

Aims. The Exeter V40 cemented polished tapered stem system has demonstrated excellent long-term outcomes. This paper presents a systematic review of the existing literature and reports on a large case series comparing implant fractures between the Exeter V40 series; 125 mm and conventional length stem systems. Methods. A systematic literature search was performed adhering to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) criteria. In parallel, we performed a retrospective single centre study of Exeter V40 femoral stem prosthetic fractures between April 2003 and June 2020. Results. There are 25 reported cases of such prosthetic fractures confined to small case series and case reports within the literature. We report an additional 19 cases to the literature (mean age 66.3 years (SD 11.7); 12 (63%) females; BMI 32.9 kg/m. 2. (SD 5.9)). The mean time from index procedure to fracture was 7.8 years (SD 3.6; 2.5 to 16.3). Exeter V40 stem fracture incidence was 0.15% and 1.21% for primary and revision arthroplasty, respectively. Incidence was significantly higher in revision arthroplasty (p < 0.001) and 125 mm length stems compared to ≥ 150 mm length stems (1.25% vs 0.13%, respectively; p < 0.001). When comparing different stem length cohorts, 125 mm short-stems were associated with stem-body fractures (92% vs 29%; p = 0.0095), earlier time to fracture (6.2 years vs 11.0 years; p = 0.0018), younger patient age at time of fracture (62.7 years vs 72.6 years; p = 0.037), and female sex (75% vs 43%; p = 0.326). Conclusion. This complication remains rare, although we report a significantly higher incidence at up to 17 years follow-up than in the literature. Short 125 mm length Exeter V40 stems undoubtedly have a role in restoring anatomy and biomechanics in smaller femoral geometries, although the surgeon has to appreciate the higher risk of stem fracture and the associated predisposing factors which may necessitate particular attention to surgical technique and planning. Cite this article: Bone Jt Open 2021;2(6):443–456

Aims. There are concerns regarding initial stability and early periprosthetic fractures in cementless hip arthroplasty using short stems. This study aimed to investigate stress on the cortical bone around the stem and micromotions between the stem and cortical bone according to femoral stem length and positioning. Methods. In total, 12 femoral finite element models (FEMs) were constructed and tested in walking and stair-climbing. Femoral stems of three different lengths and two different positions were simulated, assuming press-fit fixation within each FEM. Stress on the cortical bone and micromotions between the stem and bone were measured in each condition. Results. Stress concentration was observed on the medial and lateral interfaces between the cortical bone and stem. With neutral stem insertion, mean stress over a region of interest was greater at the medial than lateral interface regardless of stem length, which increased as the stem shortened. Mean stress increased in the varus-inserted stems compared to the stems inserted neutrally, especially at the lateral interface in contact with the stem tip. The maximum stress was observed at the lateral interface in a varus-inserted short stem. All mean stresses were greater in stair-climbing condition than walking. Each micromotion was also greater in shorter stems and varus-inserted stems, and in stair-climbing condition. Conclusion. The stem should be inserted neutrally and stair-climbing movement should be avoided in the early postoperative period, in order to preserve early stability and reduce the possibility of thigh pain, especially when using a shorter stem. Cite this article: Bone Joint Res 2021;10(4):250–258

Aims. The aim of this study was to compare the pattern of initial fixation and changes in periprosthetic bone mineral density (BMD) between patients who underwent total hip arthroplasty (THA) using a traditional fully hydroxyapatite (HA)-coated stem (T-HA group) and those with a newly introduced fully HA-coated stem (N-HA group). Methods. The study included 36 patients with T-HA stems and 30 with N-HA stems. Dual-energy X-ray absorptiometry was used to measure the change in periprosthetic BMD, one and two years postoperatively. The 3D contact between the stem and femoral cortical bone was evaluated using a density-mapping system, and clinical assessment, including patient-reported outcome measurements, was recorded. Results. There were significantly larger contact areas in Gruen zones 3, 5, and 6 in the N-HA group than in the T-HA group. At two years postoperatively, there was a significant decrease in BMD around the proximal-medial femur (zone 6) in the N-HA group and a significant increase in the T-HA group. BMD changes in both groups correlated with BMI or preoperative lumbar BMD rather than with the extent of contact with the femoral cortical bone. Conclusion. The N-HA-coated stem showed a significantly larger contact area, indicating a distal fixation pattern, compared with the traditional fully HA-coated stem. The T-HA-coated stem showed better preservation of periprosthetic BMD, two years postoperatively. Surgeons should consider these patterns of fixation and differences in BMD when selecting fully HA-coated stems for THA, to improve the long-term outcomes. Cite this article: Bone Joint J 2024;106-B(6):548–554

Aims. Uncemented implants are now commonly used at reimplantation of a two-stage revision total hip arthoplasty (THA) following periprosthetic joint infection (PJI). However, there is a paucity of data on the performance of the most commonly used uncemented femoral implants – modular fluted tapered (MFT) femoral components – in this setting. This study evaluated implant survival, radiological results, and clinical outcomes in a large cohort of reimplantation THAs using MFT components. Methods. We identified 236 reimplantation THAs from a single tertiary care academic institution from September 2000 to September 2020. Two designs of MFT femoral components were used as part of an established two-stage exchange protocol for the treatment of PJI. Mean age at reimplantation was 65 years (SD 11), mean BMI was 32 kg/m. 2. (SD 7), and 46% (n = 109) were female. Mean follow-up was seven years (SD 4). A competing risk model accounting for death was used. Results. The 15-year cumulative incidence of any revision was 24%. There were 48 revisions, with the most common reasons being dislocation (n = 25) and infection (n = 16). The 15-year cumulative incidence of any reoperation was 28%. Only 13 revisions involved the fluted tapered component (FTC), for a 15-year cumulative incidence of any FTC revision of 8%. Only two FTCs were revised for aseptic loosening, resulting in a 15-year cumulative incidence of FTC revision for aseptic loosening of 1%. Stem subsidence ≥ 5 mm occurred in 2% of unrevised cases. All stems were radiologically stable at most recent follow-up. Mean Harris Hip Score was 69 (SD 20) at most recent follow-up. Conclusion. This series demonstrated that MFT components were durable and reliable in the setting of two-stage reimplantation THA for infection. While the incidence of aseptic loosening was very low, the incidence of any revision was 24% at 15 years, primarily due to dislocation and recurrent PJI. Cite this article: Bone Joint J 2024;106-B(5 Supple B):125–132

Aims. Porous metaphyseal cones can be used for fixation in revision total knee arthroplasty (rTKA) and complex TKAs. This metaphyseal fixation has led to some surgeons using shorter cemented stems instead of diaphyseal engaging cementless stems with a potential benefit of ease of obtaining proper alignment without being beholden to the diaphysis. The purpose of this study was to evaluate short term clinical and radiographic outcomes of a series of TKA cases performed using 3D-printed metaphyseal cones. Methods. A retrospective review of 86 rTKAs and nine complex primary TKAs, with an average age of 63.2 years (SD 8.2) and BMI of 34.0 kg/m. 2. (SD 8.7), in which metaphyseal cones were used for both femoral and tibial fixation were compared for their knee alignment based on the type of stem used. Overall, 22 knees had cementless stems on both sides, 52 had cemented stems on both sides, and 15 had mixed stems. Postoperative long-standing radiographs were evaluated for coronal and sagittal plane alignment. Adjusted logistic regression models were run to assess malalignment hip-knee-ankle (HKA) alignment beyond ± 3° and sagittal alignment of the tibial and femoral components ± 3° by stem type. Results. No patients had a revision of a cone due to aseptic loosening; however, two had revision surgery due to infection. In all, 26 (27%) patients had HKA malalignment; nine (9.5%) patients had sagittal plane malalignment, five (5.6%) of the tibia, and four (10.8%) of the femur. After adjusting for age, sex, and BMI, there was a significantly increased risk for malalignment when a cone was used and both the femur and tibia had cementless compared to cemented stems (odds ratio 3.19, 95% confidence interval 1.01 to 10.05). Conclusion. Porous 3D-printed cones provide excellent metaphyseal fixation. However, these central cones make the use of offset couplers difficult and may generate malalignment with cementless stems. We found 3.19-times higher odds of malalignment in our TKAs performed with metaphyseal cones and both femoral and tibial cementless stems. Cite this article: Bone Joint J 2021;103-B(6 Supple A):150–157

Aims. It has been hypothesized that proximal radial neck resorption (PRNR) following press-fit radial head arthroplasty (RHA) is due to stress-shielding. We compared two different press-fit stems by means of radiographs to investigate whether the shape and size of the stems are correlated with the degree of PRNR. Methods. The radiographs of 52 RHAs were analyzed both at 14 days postoperatively and after two years. A cylindrical stem and a conical stem were implanted in 22 patients (group 1) and 30 patients (group 2), respectively. The PRNR was measured in the four quadrants of the radial neck and the degree of stem filling was calculated by analyzing the ratio between the prosthetic stem diameter (PSD) and the medullary canal diameter (MCD) at the proximal portion of the stem (level A), halfway along the stem length (level B), and distally at the stem tip (level C). Results. Overall, 50 of the 52 patients displayed PRNR. The mean PRNR observed was 3.9 mm (0 to 7.4). The degree of endomedullary stem filling at levels A, B, and C was 96%, 90%, and 68% in group 1, and 96%, 72%, and 57%, in group 2, with differences being significant at levels B (p < 0.001) and C (p < 0.001). No significant correlations emerged between the severity of PRNR and the three stem/canal ratios either within each group or between the groups. Conclusion. PRNR in press-fit RHA appears to be independent of the shape and size of the stems. Other causes besides stem design should be investigated to explain completely this phenomenon. Cite this article: Bone Joint J 2021;103-B(3):530–535

Aims. The involvement of long non-coding RNA (lncRNA) in bone marrow mesenchymal stem cell (MSC) osteogenic differentiation during osteoporosis (OP) development has attracted much attention. In this study, we aimed to disclose how LINC01089 functions in human mesenchymal stem cell (hMSC) osteogenic differentiation, and to study the mechanism by which LINC01089 regulates MSC osteogenesis. Methods. Quantitative reverse transcription polymerase chain reaction (RT-qPCR) and western blotting were performed to analyze LINC01089, miR-1287-5p, and heat shock protein family A (HSP70) member 4 (HSPA4) expression. The osteogenic differentiation of MSCs was assessed through alkaline phosphatase (ALP) activity, alizarin red S (ARS) staining, and by measuring the levels of osteogenic gene marker expressions using commercial kits and RT-qPCR analysis. Cell proliferative capacity was evaluated via the Cell Counting Kit-8 (CCK-8) assay. The binding of miR-1287-5p with LINC01089 and HSPA4 was verified by performing dual-luciferase reporter and RNA immunoprecipitation (RIP) experiments. Results. LINC01089 expression was reinforced in serum samples of OP patients, but it gradually diminished while hMSCs underwent osteogenic differentiation. LINC01089 knockdown facilitated hMSC osteogenic differentiation. This was substantiated by: the increase in ALP activity; ALP, runt-related transcription factor 2 (RUNX2), osteocalcin (OCN), and osteopontin (OPN) messenger RNA (mRNA) levels; and level of ARS staining. Meanwhile, LINC01089 upregulation resulted in the opposite effects. LINC01089 targeted miR-1287-5p, and the LINC01089 knockdown-induced hMSC osteogenic differentiation was repressed by miR-1287-5p depletion. HSPA4 is a downstream function molecule of the LINC01089/miR-1287-5p pathway; miR-1287-5p negatively modulated HSPA4 levels and attenuated its functional effects. Conclusion. LINC01089 negatively regulated hMSC osteogenic differentiation, at least in part, via governing miR-1287-5p/HSPA4 signalling. These findings provide new insights into hMSC osteogenesis and bone metabolism. Cite this article: Bone Joint Res 2024;13(12):779–789

Aims. The purpose of this study was to compare clinical results, long-term survival, and complication rates of stemless shoulder prosthesis with stemmed anatomical shoulder prostheses for treatment of osteoarthritis and to analyze radiological bone changes around the implants during follow-up. Methods. A total of 161 patients treated with either a stemmed or a stemless shoulder arthroplasty for primary osteoarthritis of the shoulder were evaluated with a mean follow-up of 118 months (102 to 158). The Constant score (CS), the Disabilities of the Arm, Shoulder and Hand (DASH) score, and active range of motion (ROM) were recorded. Radiological analysis for bone adaptations was performed by plain radiographs. A Kaplan-Meier survivorship analysis was calculated and complications were noted. Results. The ROM (p < 0.001), CS (p < 0.001), and DASH score (p < 0.001) showed significant improvements after shoulder arthroplasty for both implants. There were no differences between the groups treated with stemmed or stemless shoulder prosthesis with respect to the mean CS (79.2 (35 to 118) vs 74.4 (31 to 99); p = 0.519) and DASH scores (11.4 (8 to 29) vs 13.2 (7 to 23); p = 0.210). The ten-year unadjusted cumulative survival rate was 95.3% for the stemmed anatomical shoulder prosthesis and 91.5% for the stemless shoulder prosthesis and did not differ between the treatment groups (p = 0.251). The radiological evaluation of the humeral components in both groups did not show loosening of the humeral implant. The main reason for revision for each type of arthroplasties were complications related to the glenoid. Conclusion. The use of anatomical stemless shoulder prosthesis yielded good and reliable results and did not differ from anatomical stemmed shoulder prosthesis over a mean period of ten years. The differences in periprosthetic humeral bone adaptations between both implants have no clinical impact during the follow-up. Cite this article: Bone Joint J 2021;103-B(7):1292–1300

Aims. The aim of this prospective cohort study was to evaluate the early migration of the TriFit cementless proximally coated tapered femoral stem using radiostereometric analysis (RSA). Methods. A total of 21 patients (eight men and 13 women) undergoing primary total hip arthroplasty (THA) for osteoarthritis of the hip were recruited in this study and followed up for two years. Two patients were lost to follow-up. All patients received a TriFit stem and Trinity Cup with a vitamin E-infused highly cross-linked ultra-high molecular weight polyethylene liner. Radiographs for RSA were taken postoperatively and then at three, 12, and 24 months. Oxford Hip Score (OHS), EuroQol five-dimension questionnaire (EQ-5D), and adverse events were reported. Results. At two years, the mean subsidence of the head and tip for the TriFit stem was 0.38 mm (SD 0.32) and 0.52 mm (SD 0.36), respectively. The total migration of the head and tip was 0.55 mm (SD 0.32) and 0.71 mm (SD 0.38), respectively. There were no statistically significant differences between the three to 12 months' migration (p = 0.105) and 12 to 24 months' migration (p = 0.694). The OHS and EQ-5D showed significant improvements at two years. Conclusion. The results of this study suggest that the TriFit femoral stem achieves initial stability and is likely to be stable in the mid and long term. A long-term outcome study is required to assess late mechanisms of failure and the effects of bone mineral density (BMD) related changes. Cite this article: Bone Joint J 2021;103-B(4):644–649

Aims. When performing revision total hip arthroplasty using diaphyseal-engaging titanium tapered stems (TTS), the recommended 3 to 4 cm of stem-cortical diaphyseal contact may not be available. In challenging cases such as these with only 2 cm of contact, can sufficient axial stability be achieved and what is the benefit of a prophylactic cable? This study sought to determine, first, whether a prophylactic cable allows for sufficient axial stability when the contact length is 2 cm, and second, if differing TTS taper angles (2° vs 3.5°) impact these results. Methods. A biomechanical matched-pair cadaveric study was designed using six matched pairs of human fresh cadaveric femora prepared so that 2 cm of diaphyseal bone engaged with 2° (right femora) or 3.5° (left femora) TTS. Before impaction, three matched pairs received a single 100 lb-tensioned prophylactic beaded cable; the remaining three matched pairs received no cable adjuncts. Specimens underwent stepwise axial loading to 2600 N or until failure, defined as stem subsidence > 5 mm. Results. All specimens without cable adjuncts (6/6 femora) failed during axial testing, while all specimens with a prophylactic cable (6/6) successfully resisted axial load, regardless of taper angle. In total, four of the failed specimens experienced proximal longitudinal fractures, three of which occurred with the higher 3.5° TTS. One fracture occurred in a 3.5° TTS with a prophylactic cable yet passed axial testing, subsiding < 5 mm. Among specimens with a prophylactic cable, the 3.5° TTS resulted in lower mean subsidence (0.5 mm (SD 0.8)) compared with the 2° TTS (2.4 mm (SD 1.8)). Conclusion. A single prophylactic beaded cable dramatically improved initial axial stability when stem-cortex contact length was 2 cm. All implants failed secondary to fracture or subsidence > 5 mm when a prophylactic cable was not used. A higher taper angle appears to decrease the magnitude of subsidence but increased the fracture risk. The fracture risk was mitigated by the use of a prophylactic cable. Cite this article: Bone Jt Open 2023;4(7):472–477

Aims. This study evaluates risk factors influencing fracture characteristics for postoperative periprosthetic femoral fractures (PFFs) around cemented stems in total hip arthroplasty. Methods. Data were collected for PFF patients admitted to eight UK centres between 25 May 2006 and 1 March 2020. Radiographs were assessed for Unified Classification System (UCS) grade and AO/OTA type. Statistical comparisons investigated relationships by age, gender, and stem fixation philosophy (polished taper-slip (PTS) vs composite beam (CB)). The effect of multiple variables was estimated using multinomial logistic regression to estimate odds ratios (ORs) with 95% confidence intervals (CIs). Surgical treatment (revision vs fixation) was compared by UCS grade and AO/OTA type. Results. A total of 584 cases were included. Median age was 79.1 years (interquartile range 72.0 to 86.0), 312 (53.6%) patients were female, and 495 (85.1%) stems were PTS. The commonest UCS grade was type B1 (278, 47.6%). The most common AO/OTA type was spiral (352, 60.3%). Metaphyseal split fractures occurred only with PTS stems with an incidence of 10.1%. Male sex was associated with a five-fold reduction in odds of a type C fracture (OR 0.22 (95% CI 0.12 to 0.41); p < 0.001) compared to a type B fracture. CB stems were associated with significantly increased odds of transverse fracture (OR 9.51 (95% CI 3.72 to 24.34); p < 0.001) and wedge fracture (OR 3.72 (95% CI 1.16 to 11.95); p = 0.027) compared to PTS stems. Both UCS grade and AO/OTA type differed significantly (p < 0.001 and p = 0.001, respectively) between the revision and fixation groups but a similar proportion of B1 fractures underwent revision compared to fixation (45.3% vs 50.6%). Conclusion. The commonest fracture types are B1 and spiral fractures. PTS stems are exclusively associated with metaphyseal split fractures, but their incidence is low. Males have lower odds of UCS grade C fractures compared to females. CB stems have higher odds of bending type fractures (transverse and wedge) compared to PTS stems. There is considerable variation in practice when treating B1 fractures around cemented stems. Cite this article: Bone Jt Open 2021;2(7):466–475

Aims. Short, bone-conserving femoral components are increasingly used in total hip arthroplasty (THA). They are expected to allow tissue-conserving implantation and to render future revision surgery more straightforward but the long-term data on such components is limited. One such component is the global tissue-sparing (GTS) stem. Following the model for stepwise introduction of new orthopaedic implants, we evaluated early implant fixation and clinical outcome of this novel short-stem THA and compared it to that of a component with established good long-term clinical outcome. Methods. In total, 50 consecutive patients ≤ 70 years old with end-stage symptomatic osteo-arthritis were randomized to receive THA with the GTS stem or the conventional Taperloc stem using the anterior supine intermuscular approach by two experienced hip surgeons in two hospitals in the Netherlands. Primary outcome was implant migration. Patients were followed using routine clinical examination, patient reported outcome using Harris Hip Score (HHS), Hip Disability And Osteoarthritis Outcome Score (HOOS), EuroQol five-dimension questionnaire (EQ5D), and Roentgen Stereophotogrammetric Analysis (RSA) at three, six, 12, and 24 months. This study evaluated the two-year follow-up results. Results. In addition to the initial migration pattern of distal migration (subsidence, Y-translation) and retroversion (Y-rotation) also exhibited by the Taperloc stem, the GTS stem showed an initial migration pattern of varization (X-translation combined with Z-rotation) and posterior translation (Z-translation). However, all components stabilized aside from one Taperloc stem which became loose secondary to malposition and was later revised. Clinical outcomes and complications were not statistically significantly different with the numbers available. Conclusion. A substantially different and more extensive initial migration pattern was seen for the GTS stem compared to the Taperloc stem. Although implant stabilization was achieved, excellent long-term survival similar to that of the Taperloc stem should not be inferred. Especially in the absence of clinically proven relevant improvement, widespread usage should be postponed until long-term safety has been established. Cite this article: Bone Joint J 2020;102-B(6):699–708

Bone regeneration and repair are crucial to ambulation and quality of life. Factors such as poor general health, serious medical comorbidities, chronic inflammation, and ageing can lead to delayed healing and nonunion of fractures, and persistent bone defects. Bioengineering strategies to heal bone often involve grafting of autologous bone marrow aspirate concentrate (BMAC) or mesenchymal stem cells (MSCs) with biocompatible scaffolds. While BMAC shows promise, variability in its efficacy exists due to discrepancies in MSC concentration and robustness, and immune cell composition. Understanding the mechanisms by which macrophages and lymphocytes – the main cellular components in BMAC – interact with MSCs could suggest novel strategies to enhance bone healing. Macrophages are polarized into pro-inflammatory (M1) or anti-inflammatory (M2) phenotypes, and influence cell metabolism and tissue regeneration via the secretion of cytokines and other factors. T cells, especially helper T1 (Th1) and Th17, promote inflammation and osteoclastogenesis, whereas Th2 and regulatory T (Treg) cells have anti-inflammatory pro-reconstructive effects, thereby supporting osteogenesis. Crosstalk among macrophages, T cells, and MSCs affects the bone microenvironment and regulates the local immune response. Manipulating the proportion and interactions of these cells presents an opportunity to alter the local regenerative capacity of bone, which potentially could enhance clinical outcomes. Cite this article: Bone Joint Res 2024;13(9):462–473

Polished, tapered stems are now widely used for cemented total hip replacement and many such designs have been introduced. However, a change in stem geometry may have a profound influence on stability. Stems with a wide, rectangular proximal section may be more stable than those which are narrower proximally. We examined the influence of proximal geometry on stability by comparing the two-year migration of the Exeter stem with a more recent design, the CPS-Plus, which has a wider shoulder and a more rectangular cross-section. The hypothesis was that these design features would increase rotational stability. Both stems subsided approximately 1 mm relative to the femur during the first two years after implantation. The Exeter stem was found to rotate into valgus (mean 0.2°, . sd. 0.42°) and internally rotate (mean 1.28°, . sd. 0.99°). The CPS-Plus showed no significant valgus rotation (mean 0.2°, . sd. 0.42°) or internal rotation (mean −0.03°, . sd. 0.75°). A wider, more rectangular cross-section improves rotational stability and may have a better long-term outcome

Aims. BoneMaster is a thin electrochemically applied hydroxyapatite (HA) coating for orthopaedic implants that is quickly resorbed during osseointegration. Early stabilization is a surrogacy marker of good survival of femoral stems. The hypothesis of this study was that a BoneMaster coating yields a fast early and lasting fixation of stems. Methods. A total of 53 patients were randomized to be treated using Bi-Metric cementless femoral stems with either only a porous titanium plasma-sprayed coating (P group) or a porous titanium plasma-sprayed coating with an additional BoneMaster coating (PBM group). The patients were examined with radiostereometry until five years after surgery. Results. At three months, the mean total translation (TT) was 0.95 mm (95% confidence interval (CI) 0.68 to 1.22) in the P group and 0.57 mm (95% CI 0.31 to 0.83) in the PBM group (p = 0.047). From two to five years, the TT increased by a mean of 0.14 mm (95% CI 0.03 to 0.25) more in the P group than in the PBM group (p = 0.021). In osteopenic patients (n = 20), the mean TT after three months was 1.61 mm (95% CI 1.03 to 2.20) in the P group and 0.73 mm (95% CI 0.25 to 1.21) in the PBM group (p = 0.023). After 60 months, the mean TT in osteopenic patients was 1.87 mm (95% CI 1.24 to 2.50) in the P group and 0.82 mm (95% CI 0.30 to 1.33) in the PBM group (p = 0.011). Conclusion. There was less early and midterm migration of cementless stems with BoneMaster coating compared with those with only a porous titanium plasma-sprayed coating. Although a BoneMaster coating seems to be important for stem fixation, especially in osteopenic patients, further research is warranted. Cite this article: Bone Joint J 2022;104-B(6):647–656

Aims. This aim of this study was to assess the reliability and validity of the Unified Classification System (UCS) for postoperative periprosthetic femoral fractures (PFFs) around cemented polished taper-slip (PTS) stems. Methods. Radiographs of 71 patients with a PFF admitted consecutively at two centres between 25 February 2012 and 19 May 2020 were collated by an independent investigator. Six observers (three hip consultants and three trainees) were familiarized with the UCS. Each PFF was classified on two separate occasions, with a mean time between assessments of 22.7 days (16 to 29). Interobserver reliability for more than two observers was assessed using percentage agreement and Fleiss’ kappa statistic. Intraobserver reliability between two observers was calculated with Cohen kappa statistic. Validity was tested on surgically managed UCS type B PFFs where stem stability was documented in operation notes (n = 50). Validity was assessed using percentage agreement and Cohen kappa statistic between radiological assessment and intraoperative findings. Kappa statistics were interpreted using Landis and Koch criteria. All six observers were blinded to operation notes and postoperative radiographs. Results. Interobserver reliability percentage agreement was 58.5% and the overall kappa value was 0.442 (moderate agreement). Lowest kappa values were seen for type B fractures (0.095 to 0.360). The mean intraobserver reliability kappa value was 0.672 (0.447 to 0.867), indicating substantial agreement. Validity percentage agreement was 65.7% and the mean kappa value was 0.300 (0.160 to 0.4400) indicating only fair agreement. Conclusion. This study demonstrates that the UCS is unsatisfactory for the classification of PFFs around PTS stems, and that it has considerably lower reliability and validity than previously described for other stem types. Radiological PTS stem loosening in the presence of PFF is poorly defined and formal intraoperative testing of stem stability is recommended. Cite this article: Bone Joint J 2021;103-B(8):1339–1344

Aims. Although the short stem concept in hip arthroplasty procedure shows acceptable clinical performance, we sometimes get unexplainable radiological findings. The aim of this retrospective study was to evaluate changes of radiological findings up to three years postoperatively, and to assess any potential contributing factors on such radiological change in a Japanese population. Methods. This is a retrospective radiological study conducted in Japan. Radiological assessment was done in accordance with predetermined radiological review protocol. A total of 241 hips were included in the study and 118 hips (49.0%) revealed radiological change from immediately after surgery to one year postoperatively; these 118 hips were eligible for further analyses. Each investigator screened whether either radiolucent lines (RLLs), cortical hypertrophy (CH), or atrophy (AT) appeared or not on the one-year radiograph. Further, three-year radiographs of eligible cases were reviewed to determine changes such as, disappeared (D), improved (I), stable (S), and progression (P). Additionally, bone condensation (BC) was assessed on the three-year radiograph. Results. CH was observed in 49 hips (21.1%), AT was observed in 63 hips (27.2%), and RLLs were observed in 34 hips (14.7%) at one year postoperatively. Among 34 hips with RLLs, 70.6% showed change of either D or I on the three-year radiograph. BC was observed in younger patients more frequently. Conclusion. The Fitmore stem works well in a Japanese population with favourable radiological change on hips with RLLs. Longer-term follow-up is required to determine clinical relevance. Cite this article: Bone Jt Open 2022;3(1):20–28

Aims. Bone demonstrates good healing capacity, with a variety of strategies being utilized to enhance this healing. One potential strategy that has been suggested is the use of stem cells to accelerate healing. Methods. The following databases were searched: MEDLINE, CENTRAL, EMBASE, Cochrane Database of Systematic Reviews, WHO-ICTRP, ClinicalTrials.gov, as well as reference checking of included studies. The inclusion criteria for the study were: population (any adults who have sustained a fracture, not including those with pre-existing bone defects); intervention (use of stem cells from any source in the fracture site by any mechanism); and control (fracture healing without the use of stem cells). Studies without a comparator were also included. The outcome was any reported outcomes. The study design was randomized controlled trials, non-randomized or observational studies, and case series. Results. In all, 94 eligible studies were identified. The clinical and methodological aspects of the studies were too heterogeneous for a meta-analysis to be undertaken. A narrative synthesis examined study characteristics, stem cell methods (source, aspiration, concentration, and application) and outcomes. Conclusion. Insufficient high-quality evidence is available to determine the efficacy of stem cells for fracture healing. The studies were heterogeneous in population, methods, and outcomes. Work to address these issues and establish standards for future research should be undertaken. Cite this article: Bone Joint Open 2020;1-10:628–638

Aims. The direct anterior (DA) approach has been associated with rapid patient recovery after total hip arthroplasty (THA) but may be associated with more frequent femoral complications including implant loosening. The objective of this study was to determine whether the addition of a collar to the femoral stem affects implant migration, patient activity, and patient function following primary THA using the DA approach. Methods. Patients were randomized to either a collared (n = 23) or collarless (n = 26) cementless femoral stem implanted using the DA approach. Canal fill ratio (CFR) was measured on the first postoperative radiographs. Patients underwent a supine radiostereometric analysis (RSA) exam postoperatively on the day of surgery and at two, four, six, 12, 26, and 52 weeks postoperatively. Patient-reported outcome measures (Western Ontario and McMaster Universities Osteoarthritis (WOMAC) Index, the 12-item Short Form Health Survey Mental and Physical Score, and University of California, Los Angeles (UCLA) Activity Score) were measured preoperatively and at each post-surgery clinic visit. Activity and function were also measured as the weekly average step count recorded by an activity tracker, and an instrumented timed up-and-go (TUG) test in clinic, respectively. Results. Comparing the RSA between the day of surgery baseline exam to two weeks postoperatively, subsidence was significantly lower (mean difference 2.23 mm (SD 0.71), p = 0.023) with collared stems, though these patients had a greater CFR (p = 0.048). There was no difference (p = 0.426) in subsidence between stems from a two-week baseline through to one year postoperatively. There were no clinically relevant differences in PROMs; and there was no difference in the change in activity (p = 0.078) or the change in functional capacity (p = 0.664) between the collared stem group and the collarless stem group at any timepoint. Conclusion. Presence of a collar on the femoral stem resulted in reduced subsidence during the first two postoperative weeks following primary THA using the DA approach. However, the clinical implications are unclear, and larger studies examining patient activity and outcomes are required. Cite this article: Bone Joint J 2020;102-B(12):1654–1661

Aims. The purpose of our study was to determine whether mesenchymal stem cells (MSCs) are an effective and safe therapeutic agent for the treatment of knee osteoarthritis (OA), owing to their cartilage regeneration potential. Methods. We searched PubMed, Embase, and the Cochrane Library, with keywords including “knee osteoarthritis” and “mesenchymal stem cells”, up to June 2019. We selected randomized controlled trials (RCTs) that explored the use of MSCs to treat knee OA. The visual analogue scale (VAS), Western Ontario and McMaster University Osteoarthritis Index (WOMAC), adverse events, and the whole-organ MRI score (WORMS) were used as the primary evaluation tools in the studies. Our meta-analysis included a subgroup analysis of cell dose and cell source. Results. Seven trials evaluating 256 patients were included in the meta-analysis. MSC treatment significantly improved the VAS (mean difference (MD), –13.24; 95% confidence intervals (CIs) –23.28 to –3.20, p = 0.010) and WOMAC (MD, –7.22; 95% CI –12.97 to –1.47, p = 0.010). The low-dose group with less than 30 million cells showed lower p-values for both the VAS and WOMAC. Adipose and umbilical cord–derived stem cells also had lower p-values for pain scores than those derived from bone marrow. Conclusion. Overall, MSC-based cell therapy is a relatively safe treatment that holds great potential for OA, evidenced by a positive effect on pain and knee function. Using low-dose (25 million) and adipose-derived stem cells is likely to achieve better results, but further research is needed. Cite this article: Bone Joint Res 2020;9(10):719–728

Aims. The aim of this study was to determine whether fixation, as opposed to revision arthroplasty, can be safely used to treat reducible Vancouver B type fractures in association with a cemented collarless polished tapered femoral stem (the Exeter). Methods. This retrospective cohort study assessed 152 operatively managed consecutive unilateral Vancouver B fractures involving Exeter stems; 130 were managed with open reduction and internal fixation (ORIF) and 22 with revision arthroplasty. Mean follow-up was 6.5 years (SD 2.6; 3.2 to 12.1). The primary outcome measure was revision of at least one component. Kaplan–Meier survival analysis was performed. Regression analysis was used to identify risk factors for revision following ORIF. Secondary outcomes included any reoperation, complications, blood transfusion, length of hospital stay, and mortality. Results. Fractures (B1 n = 74 (49%); B2 n = 50 (33%); and B3 n = 28 (18%)) occurred at median of 4.2 years (interquartile range (IQR) 1.2 to 9.2) after primary total hip arthroplasty (THA) (n = 138) or hemiarthroplasty (n = 14). Rates of revision and reoperation were significantly higher following revision arthroplasty compared to ORIF for B2 (p = 0.001) and B3 fractures (p = 0.050). Five-year survival was significantly better following ORIF: 92% (95% confidence interval (CI) 86.4% to 97.4%) versus 63% (95% CI 41.7% to 83.3%), p < 0.001. ORIF was associated with reduced blood transfusion requirement and reoperations, but there were no differences in medical complications, hospital stay, or mortality between surgical groups. No independent predictors of revision following ORIF were identified: where the bone-cement interface was intact, fixation of B2 or B3 fractures was not associated with an increased risk of revision. Conclusion. When the bone-cement interface was intact and the fracture was anatomically reducible, all Vancouver B fractures around Exeter stems could be managed with fixation as opposed to revision arthroplasty. Fixation was associated with reduced need for blood transfusion and lower risk of revision surgery compared with revision arthroplasty. Cite this article: Bone Joint J 2021;103-B(2):309–320

Aims. The aim of this study was to radiologically evaluate the quality of cement mantle and alignment achieved with a polished tapered cemented femoral stem inserted through the anterior approach and compared with the posterior approach. Methods. A comparative retrospective study of 115 consecutive hybrid total hip arthroplasties or cemented hemiarthroplasties in 110 patients, performed through anterior (n = 58) or posterior approach (n = 57) using a collarless polished taper-slip femoral stem, was conducted. Cement mantle quality and thickness were assessed in both planes. Radiological outcomes were compared between groups. Results. No significant differences were identified between groups in Barrack grade on the anteroposterior (AP) (p = 0.640) or lateral views (p = 0.306), or for alignment on the AP (p = 0.603) or lateral views (p = 0.254). An adequate cement mantle (Barrack A or B) was achieved in 77.6% (anterior group, n = 45) and in 86% (posterior group, n = 49), respectively. Multivariate analysis revealed factors associated with unsatisfactory cement mantle (Barrack C or D) included higher BMI, left side, and Dorr Type C morphology. A mean cement mantle thickness of ≥ 2 mm was achieved in all Gruen zones for both approaches. The mean cement mantle was thicker in zone 7 (p < 0.001) and thinner in zone 9 for the anterior approach (p = 0.032). Incidence of cement mantle defects between groups was similar (6.9% (n = 4) vs 8.8% (n = 5), respectively; p = 0.489). Conclusion. An adequate cement mantle and good alignment can be achieved using a collarless polished tapered femoral component inserted through the anterior approach. Cite this article: Bone Joint J 2021;103-B(7 Supple B):46–52

Aims. The aim of this study is to report the long-term outcomes of instrumented femoral revisions with impaction allograft bone grafting (IBG) using the X-change femoral revision system at 30 years after introduction of the technique. Methods. We updated the outcomes of our previous study, based on 208 consecutive revisions using IBG and the X-change femoral revision system in combination with a cemented polished stem, performed in our tertiary care institute between 1991 and 2007. Kaplan-Meier survival analyses were used to determine the survival rate of the revisions with endpoint revision for any reason and aseptic loosening. Secondary outcomes were radiological loosening and patient-reported outcome measures. Results. Mean age at revision total hip arthroplasty (THA) was 64.9 years (30 to 86). The most prevalent diagnosis for the femoral revision was aseptic loosening. At review in May 2021, 81 patients (85 hips) were still alive and 118 patients (120 hips; 58%) had died. Three patients (3 hips; 1%) were lost to follow-up at 11, 15, and 16 years after surgery, respectively. Data of all deceased and lost patients were included until final follow-up. The mean follow-up was 13.4 years (0 to 28). During the follow-up, 22 re-revisions were performed. The most common reason for re-revision was infection (n = 12; 54%). The survival with endpoint re-revision for any reason was 86% (95% confidence interval (CI) 79 to 91) at 20 years and 74% (95% CI 43 to 89) at 25 years after surgery. The survival for endpoint re-revision for aseptic loosening was 97% (95% CI 91 to 99) after both 20 and 25 years. Conclusion. We conclude that femoral IBG is a valuable technique that can reconstitute femoral bone loss in the long term. After 25 years of follow-up, few re-revisions for aseptic loosening were required. Also, the overall revision rate is very acceptable at a long follow-up. This technique is especially attractive for younger patients facing femoral revisions with extensive bone loss. Cite this article: Bone Joint J 2022;104-B(9):1039–1046

Aims. Ageing-related incompetence becomes a major hurdle for the clinical translation of adult stem cells in the treatment of osteoarthritis (OA). This study aims to investigate the effect of stepwise preconditioning on cellular behaviours in human mesenchymal stem cells (hMSCs) from ageing patients, and to verify their therapeutic effect in an OA animal model. Methods. Mesenchymal stem cells (MSCs) were isolated from ageing patients and preconditioned with chondrogenic differentiation medium, followed by normal growth medium. Cellular assays including Bromodeoxyuridine / 5-bromo-2'-deoxyuridine (BrdU), quantitative polymerase chain reaction (q-PCR), β-Gal, Rosette forming, and histological staining were compared in the manipulated human mesenchymal stem cells (hM-MSCs) and their controls. The anterior cruciate ligament transection (ACLT) rabbit models were locally injected with two millions, four millions, or eight millions of hM-MSCs or phosphate-buffered saline (PBS). Osteoarthritis Research Society International (OARSI) scoring was performed to measure the pathological changes in the affected joints after staining. Micro-CT analysis was conducted to determine the microstructural changes in subchondral bone. Results. Stepwise preconditioning approach significantly enhanced the proliferation and chondrogenic potential of ageing hMSCs at early passage. Interestingly, remarkably lower immunogenicity and senescence was also found in hM-MSCs. Data from animal studies showed cartilage damage was retarded and subchondral bone remodelling was prevented by the treatment of preconditioned MSCs. The therapeutic effect depended on the number of cells applied to animals, with the best effect observed when treated with eight millions of hM-MSCs. Conclusion. This study demonstrated a reliable and feasible stepwise preconditioning strategy to improve the safety and efficacy of ageing MSCs for the prevention of OA development. Cite this article: Bone Joint Res 2021;10(1):10–21

Aims. Several artificial bone grafts have been developed but fail to achieve anticipated osteogenesis due to their insufficient neovascularization capacity and periosteum support. This study aimed to develop a vascularized bone-periosteum construct (VBPC) to provide better angiogenesis and osteogenesis for bone regeneration. Methods. A total of 24 male New Zealand white rabbits were divided into four groups according to the experimental materials. Allogenic adipose-derived mesenchymal stem cells (AMSCs) were cultured and seeded evenly in the collagen/chitosan sheet to form cell sheet as periosteum. Simultaneously, allogenic AMSCs were seeded onto alginate beads and were cultured to differentiate to endothelial-like cells to form vascularized bone construct (VBC). The cell sheet was wrapped onto VBC to create a vascularized bone-periosteum construct (VBPC). Four different experimental materials – acellular construct, VBC, non-vascularized bone-periosteum construct, and VBPC – were then implanted in bilateral L4-L5 intertransverse space. At 12 weeks post-surgery, the bone-forming capacities were determined by CT, biomechanical testing, histology, and immunohistochemistry staining analyses. Results. At 12 weeks, the VBPC group significantly increased new bone formation volume compared with the other groups. Biomechanical testing demonstrated higher torque strength in the VBPC group. Notably, the haematoxylin and eosin, Masson’s trichrome, and immunohistochemistry-stained histological results revealed that VBPC promoted neovascularization and new bone formation in the spine fusion areas. Conclusion. The tissue-engineered VBPC showed great capability in promoting angiogenesis and osteogenesis in vivo. It may provide a novel approach to create a superior blood supply and nutritional environment to overcome the deficits of current artificial bone graft substitutes. Cite this article: Bone Joint Res 2023;12(12):722–733

Aims. To test the hypothesis that reseeded anterior cruciate ligament (ACL)-derived cells have a better ability to survive and integrate into tendon extracellular matrix (ECM) and accelerate the ligamentization process, compared to adipose-derived mesenchymal stem cells (ADMSCs). Methods. Acellularized tibialis allograft tendons were used. Tendons were randomly reseeded with ACL-derived cells or ADMSCs. ACL-derived cells were harvested and isolated from remnants of ruptured ACLs during reconstruction surgery and cultured at passage three. Cell suspensions (200 µl) containing 2 × 10. 6. ACL-derived cells or ADMSCs were prepared for the purpose of reseeding. At days 1, 3, and 7 post-reseeding, graft composites were assessed for repopulation with histological and immunohistochemical analysis. Matrix protein contents and gene expression levels were analyzed. Results. In the graft reseeded with ACL-derived cells, a large number of elongated cells that integrated into the matrix were evident at day 3 and day 7. However, in the graft reseeded with ADMSCs, only a small number of elongated cells were found integrated into the matrix. Immunofluorescence for Ki-67 and type I collagen confirmed the pronounced production of type I collagen by Ki-67-positive ACL-derived cells integrated into the ECM. A messenger RNA (mRNA) expression assay demonstrated significantly higher gene expression levels of types I (p = 0.013) and III (p = 0.050) collagen in the composites reseeded with ACL-derived cells than ADMSCs. Conclusion. ACL-derived cells, when reseeded to acellularized tendon graft, demonstrated earlier better survival and integration in the tendon ECM and resulted in higher gene expression levels of collagen, which may be essential to the normal ligamentization process compared to ADMSCs. Cite this article: Bone Joint Res 2022;11(11):777–786

Aims. The aims of this study were to evaluate the incidence of reoperation (all cause and specifically for periprosthetic femoral fracture (PFF)) and mortality, and associated risk factors, following a hemiarthroplasty incorporating a cemented collarless polished taper slip stem (PTS) for management of an intracapsular hip fracture. Methods. This retrospective study included hip fracture patients aged 50 years and older treated with Exeter (PTS) bipolar hemiarthroplasty between 2019 and 2022. Patient demographics, place of domicile, fracture type, delirium status, American Society of Anesthesiologists (ASA) grade, length of stay, and mortality were collected. Reoperation and mortality were recorded up to a median follow-up of 29.5 months (interquartile range 12 to 51.4). Cox regression was performed to evaluate independent risk factors associated with reoperation and mortality. Results. The cohort consisted of 1,619 patients with a mean age of 82.2 years (50 to 104), of whom 1,100 (67.9%) were female. In total, 29 patients (1.8%) underwent a reoperation; 12 patients (0.7%) sustained a PFF during the observation period (United Classification System (UCS)-A n = 2; UCS-B n = 5; UCS-C n = 5), of whom ten underwent surgical management. Perioperative delirium was independently associated with the occurrence of PFF (hazard ratio (HR) 5.92; p = 0.013) and surgery for UCS-B PFF (HR 21.7; p = 0.022). Neither all-cause reoperation nor PFF-related surgery was independently associated with mortality (HR 0.66; p = 0.217 and HR 0.38; p = 0.170, respectively). Perioperative delirium, male sex, older age, higher ASA grade, and pre-fracture residential status were independently associated with increased mortality risk following hemiarthroplasty (p < 0.001). Conclusion. The cumulative incidence of PFF at four years was 1.1% in elderly patients following cemented PTS hemiarthroplasty for a hip fracture. Perioperative delirium was independently associated with a PFF. However, reoperation for PPF was not independently associated with patient mortality after adjusting for patient-specific factors. Cite this article: Bone Jt Open 2024;5(4):269–276

Aims. Compared with primary total hip arthroplasty (THA), revision surgery can be challenging. The cement-in-cement femoral revision technique involves removing a femoral component from a well-fixed femoral cement mantle and cementing a new stem into the original mantle. This technique is widely used and when carried out for the correct indications, is fast, relatively inexpensive and carries a reduced short-term risk for the patient compared with the alternative of removing well-fixed cement. We report the outcomes of this procedure when two commonly used femoral stems are used. Patients and Methods. We identified 1179 cement-in-cement stem revisions involving an Exeter or a Lubinus stem reported to the Swedish Hip Arthroplasty Register (SHAR) between January 1999 and December 2015. Kaplan-Meier survival analysis was performed. Results. Survivorship is reported up to six years and was better in the Exeter group (91% standard deviation (. sd). 2.8% versus 85% . sd. 5.0%) (p = 0.02). There was, however, no significant difference in the survival of the stem and risk of re-revision for any reason (p = 0.58) and for aseptic loosening (p = 0.97), between revisions in which the Exeter stem (94% . sd. 2.2%; 98% . sd. 1.6%) was used compared with those in which the Lubinus stem (95% . sd. 3.2%; 98% . sd.  2.2%) was used. The database did not allow identification of whether a further revision was indicated for loosening of the acetabular or femoral component or both. Conclusion. The cement-in-cement technique for revision of the femoral component gave promising results using both designs of stem, six years post-operatively. Cite this article: Bone Joint J 2017;99-B(4 Supple B):27–32

Aims. Astragalus polysaccharide (APS) participates in various processes, such as the enhancement of immunity and inhibition of tumours. APS can affect osteoporosis (OP) by regulating the osteogenic differentiation of human bone mesenchymal stem cells (hBMSCs). This study was designed to elucidate the mechanism of APS in hBMSC proliferation and osteoblast differentiation. Methods. Reverse transcriptase polymerase chain reaction (RT-PCR) and Western blotting were performed to determine the expression of microRNA (miR)-760 and ankyrin repeat and FYVE domain containing 1 (ANKFY1) in OP tissues and hBMSCs. Cell viability was measured using the Cell Counting Kit-8 assay. The expression of cyclin D1 and osteogenic marker genes (osteocalcin (OCN), alkaline phosphatase (ALP), and runt-related transcription factor 2 (RUNX2)) was evaluated using quantitative reverse transcriptase polymerase chain reaction (qRT-PCR). Mineral deposits were detected through Alizarin Red S staining. In addition, Western blotting was performed to detect the ANKFY1 protein levels following the regulation of miR-760. The relationship between miR-760 and ANKFY1 was determined using a luciferase reporter assay. Results. The expression of miR-760 was upregulated in OP tissues, whereas ANKFY1 expression was downregulated. APS stimulated the differentiation and proliferation of hBMSCs by: increasing their viability; upregulating the expression levels of cyclin D1, ALP, OCN, and RUNX2; and inducing osteoblast mineralization. Moreover, APS downregulated the expression of miR-760. Overexpression of miR-760 was found to inhibit the promotive effect of APS on hBMSC differentiation and proliferation, while knockdown of miR-760 had the opposite effect. ANKFY1 was found to be the direct target of miR-760. Additionally, ANKFY1 participated in the APS-mediated regulation of miR-760 function in hBMSCs. Conclusion. APS promotes the osteogenic differentiation and proliferation of hBMSCs. Moreover, APS alleviates the effects of OP by downregulating miR-760 and upregulating ANKFY1 expression. Cite this article: Bone Joint Res 2023;12(8):476–485

Aims. To compare long-term survival of all-cemented and hybrid total hip arthroplasty (THA) using the Exeter Universal stem. Methods. Details of 1,086 THAs performed between 1999 and 2005 using the Exeter stem and either a cemented (632) or uncemented acetabular component (454) were collected from local records and the New Zealand Joint Registry. A competing risks regression survival analysis was performed with death as the competing risk with adjustments made for age, sex, approach, and bearing. Results. There were 61 revisions (9.7%; 0.82 revisions/100 observed component years, (OCYs)) in the all-cemented group and 18 (4.0%; 0.30/100 OCYs) in the hybrid group. The cumulative incidence of revision at 18 years was 12.1% for cemented and 5.2% for hybrids. There was a significantly greater risk of revision for all-cemented compared with hybrids (unadjusted sub-hazard ratio (SHR) 2.44; p = 0.001), and of revision for loosening, wear, or osteolysis (unadjusted SHR 3.77; p < 0.001). After adjustment, the increased risk of all-cause revision did not reach significance at age 70 years and above. The advantage for revision for loosening, wear, and osteolysis remained at all ages. Conclusion. This study supports the use of uncemented acetabular fixation when used in combination with the Exeter stem with improved survivorship for revision for aseptic loosening, wear, and osteolysis at all ages and for all-cause revision in patients less than 70 years. Cite this article: Bone Joint J 2020;102-B(4):414–422

Aims. A number of methods have been described to remove a well-fixed humeral implant as part of revision shoulder arthroplasty. These include the use of cortical windows and humeral osteotomies. The router bit extraction technique uses a high-speed router bit to disrupt the bone-implant interface. The implant is then struck in a retrograde fashion with a square-tip impactor and mallet. The purpose of this study was to determine the characteristics and frequency of the different techniques needed for the removal of a well-fixed humeral stem in revision shoulder arthroplasty. Patients and Methods. Between 2010 and 2018, 288 revision shoulder arthroplasty procedures requiring removal of a well-fixed humeral component were carried out at a tertiary referral centre by a single surgeon. The patient demographics, indications for surgery, and method of extraction were collected. Results. Of the 288 revisions, 284 humeral stems (98.6%) were removed using the router bit extraction technique alone. Four humeral stems (1.39%) required an additional cortical window. Humeral osteotomy was not necessary in any procedure. Most of the humeral stems removed (78.8%) were cementless. Of the four humeral stems that required a cortical window, three involved removal of a hemiarthroplasty. Two were cemented and two were cementless. Conclusion. The router bit extraction technique removed a well-fixed humeral component in a very high proportion of patients (98.6%). This method allows surgeons to avoid more invasive approaches involving a cortical window or humeral osteotomy, and their associated complications. Cite this article: Bone Joint J 2019;101-B:1280–1284

Aims. Although good clinical outcomes have been reported for monolithic tapered, fluted, titanium stems (TFTS), early results showed high rates of subsidence. Advances in stem design may mitigate these concerns. This study reports on the use of a current monolithic TFTS for a variety of indications. Methods. A multi-institutional retrospective study of all consecutive total hip arthroplasty (THA) and revision total hip arthroplasty (rTHA) patients who received the monolithic TFTS was conducted. Surgery was performed by eight fellowship-trained arthroplasty surgeons at four institutions. A total of 157 hips in 153 patients at a mean follow-up of 11.6 months (SD7.8) were included. Mean patient age at the time of surgery was 67.4 years (SD 13.3) and mean body mass index (BMI) was 28.9 kg/m. 2. (SD 6.5). Outcomes included intraoperative complications, one-year all-cause re-revisions, and subsidence at postoperative time intervals (two weeks, six weeks, six months, nine months, and one year). Results. There were eight intraoperative complications (4.9%), six of which were intraoperative fractures; none occurred during stem insertion. Six hips (3.7%) underwent re-revision within one year; only one procedure involved removal of the prosthesis due to infection. Mean total subsidence at latest follow-up was 1.64 mm (SD 2.47). Overall, 17 of 144 stems (11.8%) on which measurements could be performed had >5 mm of subsidence, and 3/144 (2.1%) had >10 mm of subsidence within one year. A univariate regression analysis found that additional subsidence after three months was minimal. A multivariate regression analysis found that subsidence was not significantly associated with periprosthetic fracture as an indication for surgery, the presence of an extended trochanteric osteotomy (ETO), Paprosky classification of femoral bone loss, stem length, or type of procedure performed (i.e. full revision vs conversion/primary). Conclusion. Advances in implant design, improved trials, a range of stem lengths and diameters, and high offset options mitigate concerns of early subsidence and dislocation with monolithic TFTS, making them a valuable option for femoral revision. Cite this article: Bone Joint J 2020;102-B(2):191–197

Aims. This study investigates the effects of intra-articular injection of adipose-derived mesenchymal stem cells (AdMSCs) and platelet-rich plasma (PRP) on lameness, pain, and quality of life in osteoarthritic canine patients. Methods. With informed owner consent, adipose tissue collected from adult dogs diagnosed with degenerative joint disease was enzymatically digested and cultured to passage 1. A small portion of cells (n = 4) surplus to clinical need were characterized using flow cytometry and tri-lineage differentiation. The impact and degree of osteoarthritis (OA) was assessed using the Liverpool Osteoarthritis in Dogs (LOAD) score, Modified Canine Osteoarthritis Staging Tool (mCOAST), kinetic gait analysis, and diagnostic imaging. Overall, 28 joints (25 dogs) were injected with autologous AdMSCs and PRP. The patients were followed up at two, four, eight, 12, and 24 weeks. Data were analyzed using two related-samples Wilcoxon signed-rank or Mann-Whitney U tests with statistical significance set at p < 0.05. Results. AdMSCs demonstrated stem cell-like characteristics. LOAD scores were significantly lower at week 4 compared with preinjection (p = 0.021). The mCOAST improved significantly after three months (p = 0.001) and six months (p = 0.001). Asymmmetry indices decreased from four weeks post-injection and remained significantly lower at six months (p = 0.025). Conclusion. These improvements in quality of life, reduction in pain on examination, and improved symmetry in dogs injected with AdMSCs and PRP support the effectiveness of this combined treatment for symptom modification in canine OA for six months. Cite this article: Bone Joint Res 2021;10(10):650–658

Cell therapies hold significant promise for the treatment of injured or diseased musculoskeletal tissues. However, despite advances in research, there is growing concern about the increasing number of clinical centres around the world that are making unwarranted claims or are performing risky biological procedures. Such providers have been known to recommend, prescribe, or deliver so called ‘stem cell’ preparations without sufficient data to support their true content and efficacy. In this annotation, we outline the current environment of stem cell-based treatments and the strategies of marketing directly to consumers. We also outline the difficulties in the regulation of these clinics and make recommendations for best practice and the identification and reporting of illegitimate providers. Cite this article: Bone Joint J 2020;102-B(2):148–154

Aims. In the repair of condylar cartilage injury, synovium-derived mesenchymal stem cells (SMSCs) migrate to an injured site and differentiate into cartilage. This study aimed to confirm that histone deacetylase (HDAC) inhibitors, which alleviate arthritis, can improve chondrogenesis inhibited by IL-1β, and to explore its mechanism. Methods. SMSCs were isolated from synovium specimens of patients undergoing temporomandibular joint (TMJ) surgery. Chondrogenic differentiation potential of SMSCs was evaluated in vitro in the control, IL-1β stimulation, and IL-1β stimulation with HDAC inhibitors groups. The effect of HDAC inhibitors on the synovium and condylar cartilage in a rat TMJ arthritis model was evaluated. Results. Interleukin (IL)-1β inhibited the chondrogenic differentiation potential of SMSCs, while the HDAC inhibitors, suberoylanilide hydroxamic acid (SAHA) and panobinostat (LBH589), attenuated inhibition of IL-1β-induced SMSC chondrogenesis. Additionally, SAHA attenuated the destruction of condylar cartilage in rat TMJ arthritis model. IL-6 (p < 0.001) and matrix metalloproteinase 13 (MMP13) (p = 0.006) were significantly upregulated after IL-1β stimulation, while SAHA and LBH589 attenuated IL-6 and MMP13 expression, which was upregulated by IL-1β in vitro. Silencing of IL-6 significantly downregulated MMP13 expression and attenuated IL-1β-induced chondrogenesis inhibition of SMSCs. Conclusion. HDAC inhibitors SAHA and LBH589 attenuated chondrogenesis inhibition of SMSC induced by IL-1β in TMJ, and inhibition of IL-6/MMP13 pathway activation contributes to this biological progress. This study provides a theoretical basis for the application of HDAC inhibitors in the treatment of TMJ arthritis. Cite this article: Bone Joint Res 2022;11(1):40–48

Aims. Circular RNAs (circRNAs) are a novel type of non-coding RNA that plays major roles in the development of diverse diseases including osteonecrosis of the femoral head (ONFH). Here, we explored the impact of hsa_circ_0066523 derived from forkhead box P1 (FOXP1) (also called circFOXP1) on bone mesenchymal stem cells (BMSCs), which is important for ONFH development. Methods. RNA or protein expression in BMSCs was analyzed by quantitative real-time polymerase chain reaction (qRT-PCR) or western blot, respectively. Cell Counting Kit 8 (CCK8) and 5-ethynyl-2’-deoxyuridine (EdU) were used to analyze cell proliferation. Alkaline phosphatase (ALP) activity, ALP staining, and Alizarin Red S staining were employed to evaluate the osteoblastic differentiation. Chromatin immunoprecipitation (ChIP), luciferase reporter, RNA pull down, and RNA immunoprecipitation (RIP) assays were combined for exploring molecular associations. Results. Circ_0066523 was upregulated in osteogenic induction process of BMSCs. Silencing circ_0066523 restrained the proliferation and osteogenic differentiation of BMSCs. Mechanistically, circ_0066523 activated phosphatidylinositol-4,5-bisphosphate 3-kinase / AKT serine/threonine kinase 1 (PI3K/AKT) pathway via recruiting lysine demethylase 5B (KDM5B) to epigenetically repress the transcription of phosphatase and tensin homolog (PTEN). Functionally, AKT signalling pathway agonist or PTEN knockdown counteracted the effects of silenced circ_0066523 on BMSC proliferation and differentiation. Conclusion. Circ_0066523 promotes the proliferation and differentiation of BMSCs by epigenetically repressing PTEN and therefore activating AKT pathway. This finding might open new avenues for the identification of therapeutic targets for osteoblast differentiation related diseases such as ONFH. Cite this article: Bone Joint Res 2021;10(8):526–535

Objectives. Bone tissue engineering is one of the fastest growing branches in modern bioscience. New methods are being developed to achieve higher grades of mineral deposition by osteogenically inducted mesenchymal stem cells. In addition to well established monolayer cell culture models, 3D cell cultures for stem cell-based osteogenic differentiation have become increasingly attractive to promote in vivo bone formation. One of the main problems of scaffold-based osteogenic cell cultures is the difficulty in quantifying the amount of newly produced extracellular mineral deposition, as a marker for new bone formation, without destroying the scaffold. In recent studies, we were able to show that . 99m. Tc-methylene diphosphonate (. 99m. Tc-MDP), a gamma radiation-emitting radionuclide, can successfully be applied as a reliable quantitative marker for mineral deposition as this tracer binds with high affinity to newly produced hydroxyapatite (HA). Methods. Within the present study, we evaluated whether this promising new method, using . 99m. Tc-hydroxydiphosphonate (. 99m. Tc-HDP), can be used to quantify the amount of newly formed extracellular HA in a 3D cell culture model. Highly porous collagen type II scaffolds were seeded with 1 × 106 human mesenchymal stem cells (hMSCs; n = 6) and cultured for 21 days in osteogenic media (group A – osteogenic (OSM) group) and in parallel in standard media (group B – negative control (CNTRL) group). After incubation with . 99m. Tc-HDP, the tracer uptake, reflected by the amount of emitted gamma counts, was measured. Results. We saw a higher uptake (up to 15-fold) of the tracer in the OSM group A compared with the CNTRL group B. Statistical analysis of the results (Student`s t-test) revealed a significantly higher amount of emitted gamma counts in the OSM group (p = 0.048). Qualitative and semi-quantitative analysis by Alizarin Red staining confirmed the presence of extracellular HA deposition in the OSM group. Conclusion. Our data indicate that . 99m. Tc-HDP labelling is a promising tool to track and quantify non-destructive local HA deposition in 3D stem cell cultures. Cite this article: T. L. Grossner, U. Haberkorn, T. Gotterbarm. . 99m. Tc-Hydroxydiphosphonate quantification of extracellular matrix mineralization in 3D human mesenchymal stem cell cultures. Bone Joint Res 2019;8:333–341. doi: 10.1302/2046-3758.87.BJR-2017-0248.R1

Aims. Femoral stems with exchangeable (modular) necks were introduced to offer surgeons an increased choice when determining the version, offset and length of the femoral neck during total hip arthroplasty (THA). It was hoped that this would improve outcomes and reduce complications, particularly dislocation. In 2010, the Australian Orthopaedic Association National Joint Replacement Registry (AOANJRR) first reported an increased rate of revision after primary THA using femoral stems with an exchangeable neck. The aim of this study was to provide a more comprehensive up-to-date analysis of primary THA using femoral stems with exchangeable and fixed necks. Materials and Methods. The data included all primary THA procedures performed for osteoarthritis (OA), reported to the AOANJRR between 01 September 1999 and 31 December 2014. There were 9289 femoral stems with an exchangeable neck and 253 165 femoral stems with a fixed neck. The characteristics of the patients and prostheses including the bearing surface and stem/neck metal combinations were examined using Cox proportional hazard ratios (HRs) and Kaplan-Meier estimates of survivorship. . Results. It was found that prostheses with an exchangeable neck had a higher rate of revision and this was evident regardless of the bearing surface or the size of the femoral head. Exchangeable neck prostheses with a titanium stem and a cobalt-chromium neck had a significantly higher rate of revision compared with titanium stem/titanium neck combinations (HR 1.83, 95% confidence interval 1.49 to 2.23, p < 0.001). Revisions were higher for these combinations compared with femoral stems with a fixed neck. Conclusion . There appears to be little evidence to support the continued use of prostheses with an exchangeable neck in primary THA undertaken for OA. Cite this article: Bone Joint J 2017;99-B:766–73

Conventional uncemented femoral implants provide dependable long-term fixation in patients with a wide range of functional requirements. Yet challenges associated with proximal–distal femoral dimensional mismatch, preservation of bone stock, and minimally invasive approaches have led to exploration into alternative implant designs. Short stem designs focusing on a stable metaphyseal fit have emerged to address these issues in total hip replacement (THR). Uncemented metaphyseal-engaging short stem implants are stable and are associated with proximal bone remodeling closer to the metaphysis when compared with conventional stems and they also have comparable clinical performances. Short stem metaphyseal-engaging implants can meet the goals of a successful THR, including tolerating a high level of patient function, as well as durable fixation. Cite this article: Bone Joint J 2013;95-B, Supple A:57–62

Aims. Varus-valgus constrained (VVC) implants are often used during revision total knee arthroplasty (TKA) to gain coronal plane stability. However, the increased mechanical torque applied to the bone-cement interface theoretically increases the risk of aseptic loosening. We assessed mid-term survivorship, complications, and clinical outcomes of a fixed-bearing VVC device in revision TKAs. Methods. A total of 416 consecutive revision TKAs (398 patients) were performed at our institution using a single fixed-bearing VVC TKA from 2007 to 2015. Mean age was 64 years (33 to 88) with 50% male (199). Index revision TKA diagnoses were: instability (n = 122, 29%), aseptic loosening (n = 105, 25%), and prosthetic joint infection (PJI) (n = 97, 23%). All devices were cemented on the epiphyseal surfaces. Femoral stems were used in 97% (n = 402) of cases, tibial stems in 95% (n = 394) of cases; all were cemented. In total, 93% (n = 389) of cases required a stemmed femoral and tibial component. Femoral cones were used in 29%, and tibial cones in 40%. Survivorship was assessed via competing risk analysis; clinical outcomes were determined using Knee Society Scores (KSSs) and range of movement (ROM). Mean follow-up was four years (2 to 10). Results. The five-year cumulative incidence of subsequent revision for aseptic loosening and instability were 2% (95% confidence interval (CI) 0.2 to 3, number at risk = 154) and 4% (95% CI 2 to 6, number at risk = 153), respectively. The five-year cumulative incidence of any subsequent revision was 14% (95% CI 10 to 18, number at risk = 150). Reasons for subsequent revision included PJI (n = 23, of whom 12 had previous PJI), instability (n = 13), and aseptic loosening (n = 11). The use of this implant without stems was found to be a significant risk factor for subsequent revision (hazard ratio (HR) 7.58 (95% CI 3.98 to 16.03); p = 0.007). KSS improved from 46 preoperatively to 81 at latest follow-up (p < 0.001). ROM improved from 96° prerevision to 108° at latest follow-up (p = 0.016). Conclusion. The cumulative incidence of subsequent revision for aseptic loosening and instability was very low at five years with this fixed-bearing VVC implant in revision TKAs. Routine use of cemented and stemmed components with targeted use of metaphyseal cones likely contributed to this low rate of aseptic loosening. Cite this article: Bone Joint J 2020;102-B(4):458–462

Objectives. The long head of the biceps (LHB) is often resected in shoulder surgery and could therefore serve as a cell source for tissue engineering approaches in the shoulder. However, whether it represents a suitable cell source for regenerative approaches, both in the inflamed and non-inflamed states, remains unclear. In the present study, inflamed and native human LHBs were comparatively characterized for features of regeneration. Methods. In total, 22 resected LHB tendons were classified into inflamed samples (n = 11) and non-inflamed samples (n = 11). Proliferation potential and specific marker gene expression of primary LHB-derived cell cultures were analyzed. Multipotentiality, including osteogenic, adipogenic, chondrogenic, and tenogenic differentiation potential of both groups were compared under respective lineage-specific culture conditions. Results. Inflammation does not seem to affect the proliferation rate of the isolated tendon-derived stem cells (TDSCs) and the tenogenic marker gene expression. Cells from both groups showed an equivalent osteogenic, adipogenic, chondrogenic and tenogenic differentiation potential in histology and real-time polymerase chain reaction (RT-PCR) analysis. Conclusion. These results suggest that the LHB tendon might be a suitable cell source for regenerative approaches, both in inflamed and non-inflamed states. The LHB with and without tendinitis has been characterized as a novel source of TDSCs, which might facilitate treatment of degeneration and induction of regeneration in shoulder surgery. Cite this article: J. Schmalzl, P. Plumhoff, F. Gilbert, F. Gohlke, C. Konrads, U. Brunner, F. Jakob, R. Ebert, A. F. Steinert. Tendon-derived stem cells from the long head of the biceps tendon: Inflammation does not affect the regenerative potential. Bone Joint Res 2019;8:414–424. DOI: 10.1302/2046-3758.89.BJR-2018-0214.R2

The use of short stems has become more popular with the increased interest in less invasive approaches for total hip arthroplasty. The curved broaches and stem can be inserted along a curved track to avoid the abductor attachments. Short stems have the potential of being more bone conserving by allowing for higher neck retention, maintenance of the medial greater trochanter, and preferential stress transfer to the proximal femur. An initial experience with 500 new short stems (Fitmore, Zimmer Orthopedics) stems used for total hip arthroplasty is reported. No stems have been revised for aseptic loosening

Aims. Exosomes derived from bone marrow mesenchymal stem cells (BMSCs) have been reported to be a promising cellular therapeutic approach for various human diseases. The current study aimed to investigate the mechanism of BMSC-derived exosomes carrying microRNA (miR)-136-5p in fracture healing. Methods. A mouse fracture model was initially established by surgical means. Exosomes were isolated from BMSCs from mice. The endocytosis of the mouse osteoblast MC3T3-E1 cell line was analyzed. CCK-8 and disodium phenyl phosphate microplate methods were employed to detect cell proliferation and alkaline phosphatase (ALP) activity, respectively. The binding of miR-136-5p to low-density lipoprotein receptor related protein 4 (LRP4) was analyzed by dual luciferase reporter gene assay. HE staining, tartrate-resistant acid phosphatase (TRAP) staining, and immunohistochemistry were performed to evaluate the healing of the bone tissue ends, the positive number of osteoclasts, and the positive expression of β-catenin protein, respectively. Results. miR-136-5p promoted fracture healing and osteoblast proliferation and differentiation. BMSC-derived exosomes exhibited an enriched miR-136-5p level, and were internalized by MC3T3-E1 cells. LRP4 was identified as a downstream target gene of miR-136-5p. Moreover, miR-136-5p or exosomes isolated from BMSCs (BMSC-Exos) containing miR-136-5p activated the Wnt/β-catenin pathway through the inhibition of LRP4 expression. Furthermore, BMSC-derived exosomes carrying miR-136-5p promoted osteoblast proliferation and differentiation, thereby promoting fracture healing. Conclusion. BMSC-derived exosomes carrying miR-136-5p inhibited LRP4 and activated the Wnt/β-catenin pathway, thus facilitating fracture healing. Cite this article: Bone Joint Res 2021;10(12):744–758

Aims. The Mathys Affinis Short is the most frequently used stemless total shoulder prosthesis in the UK. The purpose of this prospective cohort study is to report the survivorship, clinical, and radiological outcomes of the first independent series of the Affinis Short prosthesis. Methods. From January 2011 to January 2019, a total of 141 Affinis Short prostheses were implanted in 127 patients by a single surgeon. Mean age at time of surgery was 68 (44 to 89). Minimum one year and maximum eight year follow-up (mean 3.7 years) was analyzed using the Oxford Shoulder Score (OSS) at latest follow-up. Kaplan-Meier survivorship analysis was performed with implant revision as the endpoint. Most recently performed radiographs were reviewed for component radiolucent lines (RLLs) and proximal humeral migration. Results. Five shoulders underwent revision surgery (3.5%); three for rotator cuff failure, one for infection, and one for component malposition. Survivorship of the implant was 95.4% (95% confidence interval 90.1% to 97.9%) at five and nine years. Mean OSS improved significantly compared to preoperative values from 19.0 (1 to 35) to 43.3 (7 to 48) (p < 0.001). Radiological analysis was undertaken for 99 shoulders. This revealed humeral RLLs in one case (1%), glenoid RLLs in 15 cases (15.2%), and radiological rotator cuff failure in 22 cases (22.2%). Conclusion. This prospective cohort study shows encouraging short- to mid-term survivorship and clinical and radiological results for the Mathys Affinis Short, Short Stem Total Shoulder Prosthesis. Level of Evidence: IV. Cite this article: Bone Jt Open 2021;2(1):58–65

Objectives. Mesenchymal stem cells (MSCs) are of growing interest in terms of bone regeneration. Most preclinical trials utilize bone-marrow-derived mesenchymal stem cells (bMSCs), although this is not without isolation and expansion difficulties. The aim of this study was: to compare the characteristics of bMSCs and adipose-derived mesenchymal stem cells (AdMSCs) from juvenile, adult, and ovarectomized (OVX) rats; and to assess the effect of human parathyroid hormone (hPTH) 1-34 on their osteogenic potential and migration to stromal cell-derived factor-1 (SDF-1). Methods. Cells were isolated from the adipose and bone marrow of juvenile, adult, and previously OVX Wistar rats, and were characterized with flow cytometry, proliferation assays, osteogenic and adipogenic differentiation, and migration to SDF-1. Experiments were repeated with and without intermittent hPTH 1-34. Results. Juvenile and adult MSCs demonstrated significantly increased osteogenic and adipogenic differentiation and superior migration towards SDF-1 compared with OVX groups; this was the case for AdMSCs and bMSCs equally. Parathyroid hormone (PTH) increased parameters of osteogenic differentiation and migration to SDF-1. This was significant for all cell types, although it had the most significant effect on cells derived from OVX animals. bMSCs from all groups showed increased mineralization and migration to SDF-1 compared with AdMSCs. Conclusion. Juvenile MSCs showed significantly greater migration to SDF-1 and significantly greater osteogenic and adipogenic differentiation compared with cells from osteopenic rats; this was true for bMSCs and AdMSCs. The addition of PTH increased these characteristics, with the most significant effect on cells derived from OVX animals, further illustrating possible clinical application of both PTH and MSCs in bone regenerative therapies. Cite this article:L. Osagie-Clouard, A. Sanghani-Kerai, M. Coathup, R. Meeson, T. Briggs, G. Blunn. The influence of parathyroid hormone 1-34 on the osteogenic characteristics of adipose- and bone-marrow-derived mesenchymal stem cells from juvenile and ovarectomized rats. Bone Joint Res 2019;8:397–404. DOI: 10.1302/2046-3758.88.BJR-2019-0018.R1

Aims

The aim of this retrospective study was to assess the incidence of early periprosthetic femoral fracture (PFF) associated with Charnley-Kerboull (CK) femoral components cemented according to the ‘French paradox’ principles through the Hueter anterior approach (HAA) in patients older than 70 years.

Objectives. Mesenchymal stem cells have the ability to differentiate into various cell types, and thus have emerged as promising alternatives to chondrocytes in cell-based cartilage repair methods. The aim of this experimental study was to investigate the effect of bone marrow derived mesenchymal stem cells combined with platelet rich fibrin on osteochondral defect repair and articular cartilage regeneration in a canine model. Methods. Osteochondral defects were created on the medial femoral condyles of 12 adult male mixed breed dogs. They were either treated with stem cells seeded on platelet rich fibrin or left empty. Macroscopic and histological evaluation of the repair tissue was conducted after four, 16 and 24 weeks using the International Cartilage Repair Society macroscopic and the O’Driscoll histological grading systems. Results were reported as mean and standard deviation (. sd. ) and compared at different time points between the two groups using the Mann-Whitney U test, with a value < 0.05 considered statistically significant. Results. Higher cumulative macroscopic and histological scores were observed in stem cell treated defects throughout the study period with significant differences noted at four and 24 weeks (9.25, . sd. 0.5 vs 7.25, . sd. 0.95, and 10, . sd. 0.81 vs 7.5, . sd. 0.57; p < 0.05) and 16 weeks (16.5, . sd. 4.04 vs 11, . sd. 1.15; p < 0.05), respectively. Superior gross and histological characteristics were also observed in stem cell treated defects. Conclusion. The use of autologous culture expanded bone marrow derived mesenchymal stem cells on platelet rich fibrin is a novel method for articular cartilage regeneration. It is postulated that platelet rich fibrin creates a suitable environment for proliferation and differentiation of stem cells by releasing endogenous growth factors resulting in creation of a hyaline-like reparative tissue. Cite this article: D. Kazemi, K. Shams Asenjan, N. Dehdilani, H. Parsa. Canine articular cartilage regeneration using mesenchymal stem cells seeded on platelet rich fibrin: Macroscopic and histological assessments. Bone Joint Res 2017;6:98–107. DOI: 10.1302/2046-3758.62.BJR-2016-0188.R1

Objectives. Cellular movement and relocalisation are important for many physiologic properties. Local mesenchymal stem cells (MSCs) from injured tissues and circulating MSCs aid in fracture healing. Cytokines and chemokines such as Stromal cell-derived factor 1(SDF-1) and its receptor chemokine receptor type 4 (CXCR4) play important roles in maintaining mobilisation, trafficking and homing of stem cells from bone marrow to the site of injury. We investigated the differences in migration of MSCs from the femurs of young, adult and ovariectomised (OVX) rats and the effect of CXCR4 over-expression on their migration. Methods. MSCs from young, adult and OVX rats were put in a Boyden chamber to establish their migration towards SDF-1. This was compared with MSCs transfected with CXCR4, as well as MSCs differentiated to osteoblasts. Results. MSCs from OVX rats migrate significantly (p < 0.05) less towards SDF-1 (9%, . sd. 5%) compared with MSCs from adult (15%, . sd. 3%) and young rats (25%, . sd. 4%). Cells transfected with CXCR4 migrated significantly more towards SDF-1 compared with non-transfected cells, irrespective of whether these cells were from OVX (26.5%, . sd. 4%), young (47%, . sd. 17%) or adult (21%, . sd. 4%) rats. Transfected MSCs differentiated to osteoblasts express CXCR4 but do not migrate towards SDF-1. Conclusions. MSC migration is impaired by age and osteoporosis in rats, and this may be associated with a significant reduction in bone formation in osteoporotic patients. The migration of stem cells can be ameliorated by upregulating CXCR4 levels which could possibly enhance fracture healing in osteoporotic patients. Cite this article: A. Sanghani-Kerai, M. Coathup, S. Samazideh, P. Kalia, L. Di Silvio, B. Idowu, G. Blunn. Osteoporosis and ageing affects the migration of stem cells and this is ameliorated by transfection with CXCR4. Bone Joint Res 2017;6:–365. DOI: 10.1302/2046-3758.66.BJR-2016-0259.R1

Objectives. The use of ceramic femoral heads in total hip arthroplasty (THA) has increased due to their proven low bearing wear characteristics. Ceramic femoral heads are also thought to reduce wear and corrosion at the head-stem junction with titanium (Ti) stems when compared with metal heads. We sought to evaluate taper damage of ceramic compared with metal heads when paired with cobalt chromium (CoCr) alloy stems in a single stem design. Methods. This retrieval study involved 48 total hip arthroplasties (THAs) with CoCr V40 trunnions paired with either CoCr (n = 21) or ceramic (n = 27) heads. The taper junction of all hips was evaluated for fretting/corrosion damage and volumetric material loss using a roundness-measuring machine. We used linear regression analysis to investigate taper damage differences after adjusting for potential confounding variables. Results. We measured median taper material loss rates of 0.210 mm. 3. /year (0.030 to 0.448) for the metal head group and 0.084 mm. 3. /year (0.059 to 0.108) for the ceramic group. The difference was not significant (p = 0.58). Moreover, no significant correlation between material loss and implant or patient factors (p > 0.05) was found. Conclusions. Metal heads did not increase taper damage on CoCr trunnions compared with ceramic heads from the same hip design. The amount of material released at the taper junctions was very low when compared with available data regarding CoCr/Ti coupling in metal-on-metal bearings. Cite this article: A. Di Laura, H. Hothi, J. Henckel, I. Swiatkowska, M. H. L. Liow, Y-M. Kwon, J. A. Skinner, A. J. Hart. Retrieval analysis of metal and ceramic femoral heads on a single CoCr stem design. Bone Joint Res 2017;6:–350. DOI: 10.1302/2046-3758.65.BJR-2016-0325.R1

We retrospectively reviewed 175 patients (191 hips) who had undergone primary cemented total hip replacement between November 1992 and November 1995 using a collarless polished double-tapered femoral component after a minimum of ten years (mean 11.08; 10 to 12.8). All stems were implanted using contemporary cementing techniques with a distal cement restrictor, pressurised lavage, retrograde cementing with a gun and proximal pressurisation. Clinical outcome was assessed using the Harris Hip score. Radiological analysis was performed on calibrated plain radiographs taken in two planes. Complete radiological data on 110 patients (120 hips) and clinical follow-up on all the surviving 111 patients (122 hips) was available. The fate of all the hips was known. At final follow-up, the mean Harris Hip score was 86 (47 to 100), and 87 of 116 patients (75%) had good or excellent scores. Survival with revision of the stem for aseptic loosening as the endpoint was 100%; and survival with revision of the stem for any reason was 95.9% (95% confidence interval 87.8 to 96.8) at ten years. All the stems subsided vertically at the stem-cement interface in a predictable pattern, at an overall mean rate of 0.18 mm per year (0.02 to 2.16), but with a mean rate of 0.80 mm (0.02 to 2.5) during the first year. The mean total subsidence was 1.95 mm (0.21 to 24). Only three stems loosened at the cement-bone interface. There was excellent preservation of proximal femoral bone stock. There was a high incidence of Brooker III and IV heterotopic ossification affecting 25 patients (22%). The collarless polished tapered stem has an excellent clinical and radiological outcome at a minimum of ten years’ follow-up. The pattern and magnitude of subsidence of the stem within the cement mantle occurred in a predictable pattern, consistent with the design philosophy

Aims. We sought to determine whether cobalt-chromium alloy (CoCr) femoral stem tapers (trunnions) wear more than titanium (Ti) alloy stem tapers (trunnions) when used in a large diameter (LD) metal-on-metal (MoM) hip arthroplasty system. Patients and Methods. We performed explant analysis using validated methodology to determine the volumetric material loss at the taper surfaces of explanted LD CoCr MoM hip arthroplasties used with either a Ti alloy (n = 28) or CoCr femoral stem (n = 21). Only 12/14 taper constructs with a rough male taper surface and a nominal included angle close to 5.666° were included. Multiple regression modelling was undertaken using taper angle, taper roughness, bearing diameter (horizontal lever arm) as independent variables. Material loss was mapped using a coordinate measuring machine, profilometry and scanning electron microscopy. Results. After adjustment for other factors, CoCr stem tapers were found to have significantly greater volumetric material loss than the equivalent Ti stem tapers. Conclusion. When taper junction damage is identified during revision of a LD MoM hip, it should be suspected that a male taper composed of a standard CoCr alloy has sustained significant changes to the taper cone geometry which are likely to be more extensive than those affecting a Ti alloy stem. Cite this article: Bone Joint J 2017;99-B:1304–12

Progressive retroversion of a cemented stem is predictive of early loosening and failure. We assessed the relationship between direct post-operative stem anteversion, measured with CT, and the resulting rotational stability, measured with repeated radiostereometric analysis over ten years. The study comprised 60 cemented total hip replacements using one of two types of matt collared stem with a rounded cross-section. The patients were divided into three groups depending on their measured post-operative anteversion (< 10°, 10° to 25°, >  25°). There was a strong correlation between direct post-operative anteversion and later posterior rotation. At one year the < 10° group showed significantly more progressive retroversion together with distal migration, and this persisted to the ten-year follow-up. In the < 10° group four of ten stems (40%) had been revised at ten years, and an additional two stems (20%) were radiologically loose. In the ‘normal’ (10° to 25°) anteversion group there was one revised (3%) and one loose stem (3%) of a total of 30 stems, and in the > 25° group one stem (5%) was revised and another loose (5%) out of 20 stems. This poor outcome is partly dependent on the design of this prosthesis, but the results strongly suggest that the initial rotational position of cemented stems during surgery affects the subsequent progressive retroversion, subsidence and eventual loosening. The degree of retroversion may be sensitive to prosthetic design and stem size, but < 10° of anteversion appears deleterious to the long-term outcome for cemented hip prosthetic stems. Cite this article: Bone Joint J 2013;95-B:23–30

Aims

The aim of this study was to determine both the incidence of, and the reoperation rate for, postoperative periprosthetic femoral fracture (POPFF) after total hip arthroplasty (THA) with either a collared cementless (CC) femoral component or a cemented polished taper-slip (PTS) femoral component.

We reviewed 142 consecutive primary total hip replacements implanted into 123 patients between 1988 and 1993 using the Exeter Universal femoral stem. A total of 74 patients (88 hips) had survived for ten years or more and were reviewed at a mean of 12.7 years (10 to 17). There was no loss to follow-up. The rate of revision of the femoral component for aseptic loosening and osteolysis was 1.1% (1 stem), that for revision for any cause was 2.2% (2 stems), and for re-operation for any cause was 21.6% (19 hips). Re-operation was because of failure of the acetabular component in all but two hips. All but one femoral component subsided within the cement mantle to a mean of 1.52 mm (0 to 8.3) at the final follow-up. One further stem had subsided excessively (8 mm) and had lucent lines at the cement-stem and cement-bone interfaces. This was classified as a radiological failure and is awaiting revision. One stem was revised for deep infection and one for excessive peri-articular osteolysis. Defects of the cement mantle (Barrack grade C and D) were found in 28% of stems (25 hips), associated with increased subsidence (p = 0.01), but were not associated with endosteal lysis or failure. Peri-articular osteolysis was significantly related to the degree of polyethylene wear (p < 0.001), which was in turn associated with a younger age (p = 0.01) and male gender (p < 0.001). The use of the Exeter metal-backed acetabular component was a notable failure with 12 of 32 hips (37.5%) revised for loosening. The Harris-Galante components failed with excessive wear, osteolysis and dislocation with 15% revised (5 of 33 hips). Only one of 23 hips with a cemented Elite component (4%) was revised for loosening and osteolysis. Our findings show that the Exeter Universal stem implanted outside the originating centre has excellent medium-term results

The Exeter femoral stem is a double-tapered highly polished collarless cemented implant with good long-term clinical results. In order to determine why the stem functions well we have undertaken a long-term radiostereometric analysis (RSA) study. A total of 20 patients undergoing primary Exeter total hip replacement for osteoarthritis using the Hardinge approach were recruited and followed with RSA for ten years. The stems progressively subsided and internally rotated with posterior head migration. The mean subsidence was 0.7 mm (95% confidence interval (CI) 0.5 to 0.9) at two years and 1.3 mm (95% CI 1.0 to 1.6) at ten years. The mean posterior migration of the head was 0.7 mm (95% CI 0.5 to 0.9) at two years and 1.2 mm (95% CI 1.0 to 1.4) at ten years. There was no significant cement restrictor migration. The Exeter stem continues to subside slowly into the cement mantle in the long term. This appears to compress the cement and the cement bone interface, contributing to secure fixation in the long term. Cite this article: Bone Joint J 2013;95-B:605–8

Introduction. Osteoarthritis (OA) is a progressively debilitating disease that affects mostly cartilage, with associated changes in the bone. The increasing incidence of OA and an ageing population, coupled with insufficient therapeutic choices, has led to focus on the potential of stem cells as a novel strategy for cartilage repair. Methods. In this study, we used scaffold-free mesenchymal stem cells (MSCs) obtained from bone marrow in an experimental animal model of OA by direct intra-articular injection. MSCs were isolated from 2.8 kg white New Zealand rabbits. There were ten in the study group and ten in the control group. OA was induced by unilateral transection of the anterior cruciate ligament of the knee joint. At 12 weeks post-operatively, a single dose of 1 million cells suspended in 1 ml of medium was delivered to the injured knee by direct intra-articular injection. The control group received 1 ml of medium without cells. The knees were examined at 16 and 20 weeks following surgery. Repair was investigated radiologically, grossly and histologically using haematoxylin and eosin, Safranin-O and toluidine blue staining. Results. Radiological assessment confirmed development of OA changes after 12 weeks. Rabbits receiving MSCs showed a lower degree of cartilage degeneration, osteophyte formation, and subchondral sclerosis than the control group at 20 weeks post-operatively. The quality of cartilage was significantly better in the cell-treated group compared with the control group after 20 weeks. Conclusions. Bone marrow-derived MSCs could be promising cell sources for the treatment of OA. Neither stem cell culture nor scaffolds are absolutely necessary for a favourable outcome. Cite this article: Bone Joint Res 2014;3:32–7

Cemented femoral stems with force closed fixation designs have shown good clinical results despite high early subsidence. A new triple-tapered stem in this category (C-stem AMT) was introduced in 2005. This study compares this new stem with an established stem of similar design (Exeter) in terms of migration (as measured using radiostereometric analysis), peri-prosthetic bone remodelling (measured using dual energy x-ray densitometry, DXA), Oxford Hip Score, and plain radiographs. . A total of 70 patients (70 hips) with a mean age of 66 years (53 to 78) were followed for two years. Owing to missing data of miscellaneous reasons, the final analysis represents data from 51 (RSA) and 65 (DXA) patients. Both stems showed a typical pattern of migration: Subsidence and retroversion that primarily occurred during the first three months. C-stem AMT subsided less during the first three months (p = 0.01), before stabilising at a subsidence rate similar to the Exeter stem from years one to two. The rate of migration into retroversion was slightly higher for C-stem AMT during the second year (p = 0.03). Whilst there were slight differences in movement patterns between the stems, the C-stem AMT exhibits good early clinical outcomes and displays a pattern of migration and bone remodelling that predicts good clinical performance. Cite this article: Bone Joint J 2015;97-B:755–61

Objectives. In total hip arthroplasty (THA), the cementless, tapered-wedge stem design contributes to achieving initial stability and providing optimal load transfer in the proximal femur. However, loading conditions on the femur following THA are also influenced by femoral structure. Therefore, we determined the effects of tapered-wedge stems on the load distribution of the femur using subject-specific finite element models of femurs with various canal shapes. Patients and Methods. We studied 20 femurs, including seven champagne flute-type femurs, five stovepipe-type femurs, and eight intermediate-type femurs, in patients who had undergone cementless THA using the Accolade TMZF stem at our institution. Subject–specific finite element (FE) models of pre- and post-operative femurs with stems were constructed and used to perform FE analyses (FEAs) to simulate single-leg stance. FEA predictions were compared with changes in bone mineral density (BMD) measured for each patient during the first post-operative year. Results. Stovepipe models implanted with large-size stems had significantly lower equivalent stress on the proximal-medial area of the femur compared with champagne-flute and intermediate models, with a significant loss of BMD in the corresponding area at one year post-operatively. Conclusions. The stovepipe femurs required a large-size stem to obtain an optimal fit of the stem. The FEA result and post-operative BMD change of the femur suggest that the combination of a large-size Accolade TMZF stem and stovepipe femur may be associated with proximal stress shielding. Cite this article: M. Oba, Y. Inaba, N. Kobayashi, H. Ike, T. Tezuka, T. Saito. Effect of femoral canal shape on mechanical stress distribution and adaptive bone remodelling around a cementless tapered-wedge stem. Bone Joint Res 2016;5:362–369. DOI: 10.1302/2046-3758.59.2000525

Objectives. Up to 10% of fractures result in undesirable outcomes, for which female sex is a risk factor. Cellular sex differences have been implicated in these different healing processes. Better understanding of the mechanisms underlying bone healing and sex differences in this process is key to improved clinical outcomes. This study utilized a macrophage–mesenchymal stem cell (MSC) coculture system to determine: 1) the precise timing of proinflammatory (M1) to anti-inflammatory (M2) macrophage transition for optimal bone formation; and 2) how such immunomodulation was affected by male versus female cocultures. Methods. A primary murine macrophage-MSC coculture system was used to demonstrate the optimal transition time from M1 to M2 (polarized from M1 with interleukin (IL)-4) macrophages to maximize matrix mineralization in male and female MSCs. Outcome variables included Alizarin Red staining, alkaline phosphatase (ALP) activity, and osteocalcin protein secretion. Results. We found that 96 hours of M1 phenotype in male cocultures allowed for maximum matrix mineralization versus 72 hours in female cocultures. ALP activity and osteocalcin secretion were also enhanced with the addition of IL-4 later in male versus female groups. The sex of the cells had a statistically significant effect on the optimal IL-4 addition time to maximize osteogenesis. Conclusion. These results suggest that: 1) a 72- to 96-hour proinflammatory environment is critical for optimal matrix mineralization; and 2) there are immunological differences in this coculture environment due to sex. Optimizing immunomodulation during fracture healing may enhance and expedite the bone regeneration response. These findings provide insight into precise immunomodulation for enhanced bone healing that is sex-specific. Cite this article: K. Nathan, L. Y. Lu, T. Lin, J. Pajarinen, E. Jämsen, J-F. Huang, M. Romero-Lopez, M. Maruyama, Y. Kohno, Z. Yao, S. B. Goodman. Precise immunomodulation of the M1 to M2 macrophage transition enhances mesenchymal stem cell osteogenesis and differs by sex. Bone Joint Res 2019;8:481–488. DOI: 10.1302/2046-3758.810.BJR-2018-0231.R2

Aims. Here we introduce a wide and complex study comparing effects of growth factors used alone and in combinations on human mesenchymal stem cell (hMSC) proliferation and osteogenic differentiation. Certain ways of cell behaviour can be triggered by specific peptides – growth factors, influencing cell fate through surface cellular receptors. Methods. In our study transforming growth factor β (TGF-β), basic fibroblast growth factor (bFGF), hepatocyte growth factor (HGF), insulin-like growth factor 1 (IGF-1), and vascular endothelial growth factor (VEGF) were used in order to induce osteogenesis and proliferation of hMSCs from bone marrow. These cells are naturally able to differentiate into various mesodermal cell lines. Effect of each factor itself is pretty well known. We designed experimental groups where two and more growth factors were combined. We supposed cumulative effect would appear when more growth factors with the same effect were combined. The cellular metabolism was evaluated using MTS assay and double-stranded DNA (dsDNA) amount using PicoGreen assay. Alkaline phosphatase (ALP) activity, as early osteogenesis marker, was observed. Phase contrast microscopy was used for cell morphology evaluation. Results. TGF-β and bFGF were shown to significantly enhance cell proliferation. VEGF and IGF-1 supported ALP activity. Light microscopy showed initial extracellular matrix mineralization after VEGF/IGF-1 supply. Conclusion. A combination of more than two growth factors did not support the cellular metabolism level and ALP activity even though the growth factor itself had a positive effect. This is probably caused by interplay of various messengers shared by more growth factor signalling cascades. Cite this article: Bone Joint Res 2020;9(7):412–420

The aim of this study was to obtain detailed long-term data on the cement-bone interface in patients with cemented stems, implanted using the constrained fixation technique. A total of eight stems were removed together with adjacent bone during post-mortem examinations of patients with well-functioning prostheses. Specimens were cut at four defined levels, contact radiographs were obtained for each level, and slices were prepared for histological analysis. Clinical data, clinical radiographs, contact radiographs and histological samples were examined for signs of loosening and remodelling. The mean radiological follow-up was 9.6 years and all stems were well-fixed, based on clinical and radiological criteria. Contact radiographs revealed an incomplete cement mantle but a complete filling of the medullary canal for all implants. Various amounts of polyethylene particles were evident at the cement-bone interface of seven stems, with no accompanying inflammatory reaction. Cortical atrophy and the formation of an ‘inner cortex’ were confirmed in six of eight stems by contact radiographs and histology, but were only visible on two clinical radiographs. Our results confirm that a complete cement mantle is not essential for the survival of Müller straight stems into the mid term, and support our hypothesis that no benefit to long-term survival can be expected from modern cementing techniques

Tapered, fluted, modular, titanium stems have a long history in Europe and are increasing in popularity in North America. We have reviewed the results at our institution looking at stem survival and clinical outcomes. Radiological outcomes and quality of life assessments have been performed and compared to cylindrical non-modular cobalt chromium stems. Survival at five years was 94%. This fell to 85% at ten years due to stem breakage with older designs. Review of radiology showed maintenance or improvement of bone stock in 87% of cases. Outcome scores were superior in tapered stems despite worse pre-operative femoral deficiency. Tapered stems have proved to be a useful alternative in revision total hip arthroplasty across the spectrum of femoral bone deficiency

Periprosthetic femoral fracture (PFF) is a potentially devastating complication after total hip arthroplasty, with historically high rates of complication and failure because of the technical challenges of surgery, as well as the prevalence of advanced age and comorbidity in the patients at risk. This study describes the short-term outcome after revision arthroplasty using a modular, titanium, tapered, conical stem for PFF in a series of 38 fractures in 37 patients. The mean age of the cohort was 77 years (47 to 96). A total of 27 patients had an American Society of Anesthesiologists grade of at least 3. At a mean follow-up of 35 months (4 to 66) the mean Oxford Hip Score (OHS) was 35 (15 to 48) and comorbidity was significantly associated with a poorer OHS. All fractures united and no stem needed to be revised. Three hips in three patients required further surgery for infection, recurrent PFF and recurrent dislocation and three other patients required closed manipulation for a single dislocation. One stem subsided more than 5 mm but then stabilised and required no further intervention. . In this series, a modular, tapered, conical stem provided a versatile reconstruction solution with a low rate of complications. Cite this article: Bone Joint J 2015;97-B:1031–7

Aims. Periprosthetic fracture (PF) after primary total hip arthroplasty (THA) is an uncommon but potentially devastating complication. This study aims to investigate the influence of cemented stem designs on the risk of needing a revision for a PF. Patients and Methods. We analysed data on 257 202 primary THAs with cemented stems and 390 linked first revisions for PF recorded in the National Joint Registry (NJR) of England, Wales and Northern Ireland to determine if a cemented femoral stem brand was associated with the risk of having revision for a PF after primary THA. All cemented femoral stem brands with more than 10 000 primary operations recorded in the NJR were identified. The four most commonly used cemented femoral stems were the Exeter V40 (n = 146 409), CPT (n = 24 300), C-Stem (n = 15 113) and Charnley (n = 20 182). We compared the revision risk ratios due to PF amongst the stems using a Poisson regression model adjusting for patient factors. Compared with the Exeter V40, the age, gender and ASA grade adjusted revision rate ratio was 3.89 for the cemented CPT stem (95% confidence interval (CI) 3.07 to 4.93), 0.89 for the C-Stem (95% CI 0.57 to 1.41) and 0.41 for the Charnley stem (95% CI 0.24 to 0.70). Conclusions. The limitations of the study include incomplete data capture, analysis of only PF requiring revision and that observation does not imply causality. Nevertheless, this study demonstrates that the choice of a cemented stem may influence the risk of revision for PF. Cite this article: Bone Joint J 2016;98-B:1347–54

Aims. This study aimed to investigate whether human umbilical cord mesenchymal stem cells (UC-MSCs) can prevent articular cartilage degradation and explore the underlying mechanisms in a rat osteoarthritis (OA) model induced by monosodium iodoacetate (MIA). Methods. Human UC-MSCs were characterized by their phenotype and multilineage differentiation potential. Two weeks after MIA induction in rats, human UC-MSCs were intra-articularly injected once a week for three weeks. The therapeutic effect of human UC-MSCs was evaluated by haematoxylin and eosin, toluidine blue, Safranin-O/Fast green staining, and Mankin scores. Markers of joint cartilage injury and pro- and anti-inflammatory markers were detected by immunohistochemistry. Results. Histopathological analysis showed that intra-articular injection of human UC-MSCs significantly inhibited the progression of OA, as demonstrated by reduced cartilage degradation, increased Safranin-O staining, and lower Mankin scores. Immunohistochemistry showed that human UC-MSC treatment down-regulated the expression of matrix metalloproteinase-13 (MMP13) and a disintegrin and metalloproteinase with thrombospondin motifs 5 (ADAMTS-5), and enhanced the expression of type II collagen and ki67 in the articular cartilage. Furthermore, human UC-MSCs significantly decreased the expression of interleukin (IL)-1β and tumour necrosis factor-α (TNF-α), while increasing TNF-α-induced protein 6 and IL-1 receptor antagonist. Conclusion. Our results demonstrated that human UC-MSCs ameliorate MIA-induced OA by preventing cartilage degradation, restoring the proliferation of chondrocytes, and inhibiting the inflammatory response, which implies that human UC-MSCs may be a promising strategy for the treatment of OA. Cite this article: Bone Joint Res 2021;10(3):226–236

We identified five (2.3%) fractures of the stem in a series of 219 revision procedures using a cementless, cylindrical, extensively porous-coated, distally-fixed femoral stem. Factors relating to the patients, the implant and the operations were compared with those with intact stems. Finite-element analysis was performed on two of the fractured implants. Factors associated with fracture of the stem were poor proximal bone support (type III–type IV; p = 0.001), a body mass index > 30; (p = 0.014), a smaller diameter of stem (< 13.5 mm; p = 0.007) and the use of an extended trochanteric osteotomy (ETO 4/5: p = 0.028). Finite-element analysis showed that the highest stresses on the stem occurred adjacent to the site of the fracture. The use of a strut graft wired over an extended trochanteric osteotomy in patients lacking proximal femoral cortical support decreased the stresses on the stem by 48%. We recommend the use of a strut allograft in conjunction with an extended trochanteric osteotomy in patients with poor proximal femoral bone stock

Femoral revision after cemented total hip replacement (THR) might include technical difficulties, following essential cement removal, which might lead to further loss of bone and consequently inadequate fixation of the subsequent revision stem. . Femoral impaction allografting has been widely used in revision surgery for the acetabulum, and subsequently for the femur. In combination with a primary cemented stem, impaction grafting allows for femoral bone restoration through incorporation and remodelling of the impacted morsellized bone graft by the host skeleton. Cavitary bone defects affecting meta-physis and diaphysis leading to a wide femoral shaft, are ideal indications for this technique. Cancellous allograft bone chips of 1 mm to 2 mm size are used, and tapered into the canal with rods of increasing diameters. To impact the bone chips into the femoral canal a prosthesis dummy of the same dimensions of the definitive cemented stem is driven into the femur to ensure that the chips are very firmly impacted. Finally, a standard stem is cemented into the neo-medullary canal using bone cement. . To date several studies have shown favourable results with this technique, with some excellent long-term results reported in independent clinical centres worldwide. Cite this article: Bone Joint J 2013;95-B, Supple A:92–4

Aims. Non-coding microRNA (miRNA) in extracellular vesicles (EVs) derived from mesenchymal stem cells (MSCs) may promote neuronal repair after spinal cord injury (SCI). In this paper we report on the effects of MSC-EV-microRNA-381 (miR-381) in a rodent model of SCI. Methods. In the current study, the luciferase assay confirmed a binding site of bromodomain-containing protein 4 (BRD4) and Wnt family member 5A (WNT5A). Then we detected expression of miR-381, BRD4, and WNT5A in dorsal root ganglia (DRG) cells treated with MSC-isolated EVs and measured neuron apoptosis in culture by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining. A rat model of SCI was established to detect the in vivo effect of miR-381 and MSC-EVs on SCI. Results. We confirmed an interaction between miR-381 and BRD4, and showed that miR-381 overexpression inhibited the expression of BRD4 in DRG cells as well as the apoptosis of DRG cells through WNT5A via activation of Ras homologous A (RhoA)/Rho-kinase activity. Moreover, treatment of MSC-EVs rescued neuron apoptosis and promoted the recovery of SCI through inhibition of the BRD4/WNT5A axis. Conclusion. Taken altogether, miR-381 derived from MSC-EVs can promote the recovery of SCI through BRD4/WNT5A axis, providing a new perspective on SCI treatment. Cite this article: Bone Joint Res 2021;10(5):328–339

Stem cells are a key component of regenerative medicine strategies. Particular areas of musculoskeletal application include cartilage and bone regeneration in arthritis and trauma. There are several types of stem cell and this article will focus on the adult derived cells. The review includes current issues and future developments

Following the recall of modular neck hip stems in July 2012, research into femoral modularity will intensify over the next few years. This review aims to provide surgeons with an up-to-date summary of the clinically relevant evidence. The development of femoral modularity, and a classification system, is described. The theoretical rationale for modularity is summarised and the clinical outcomes are explored. The review also examines the clinically relevant problems reported following the use of femoral stems with a modular neck. Joint replacement registries in the United Kingdom and Australia have provided data on the failure rates of modular devices but cannot identify the mechanism of failure. This information is needed to determine whether modular neck femoral stems will be used in the future, and how we should monitor patients who already have them implanted. Cite this article: Bone Joint J 2013;95-B:1011–21

Objectives. Osteoporosis is a systemic bone metabolic disease, which often occurs among the elderly. Angelica polysaccharide (AP) is the main component of angelica sinensis, and is widely used for treating various diseases. However, the effects of AP on osteoporosis have not been investigated. This study aimed to uncover the functions of AP in mesenchymal stem cell (MSC) proliferation and osteoblast differentiation. Methods. MSCs were treated with different concentrations of AP, and then cell viability, Cyclin D1 protein level, and the osteogenic markers of runt-related transcription factor 2 (RUNX2), osteocalcin (OCN), alkaline phosphatase (ALP), bone morphogenetic protein 2 (BMP-2) were examined by Cell Counting Kit-8 (CCK-8) and western blot assays, respectively. The effect of AP on the main signalling pathways of phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) and Wnt/β-catenin was determined by western blot. Following this, si-H19#1 and si-H19#2 were transfected into MSCs, and the effects of H19 on cell proliferation and osteoblast differentiation in MSCs were studied. Finally, in vivo experimentation explored bone mineral density, bone mineral content, and the ash weight and dry weight of femoral bone. Results. The results revealed that AP significantly promoted cell viability, upregulated cyclin D1 and increased RUNX2, OCN, ALP, and BMP-2 protein levels in MSCs. Moreover, we found that AP notably activated PI3K/AKT and Wnt/β-catenin signalling pathways in MSCs. Additionally, the relative expression level of H19 was upregulated by AP in a dose-dependent manner. The promoting effects of AP on cell proliferation and osteoblast differentiation were reversed by H19 knockdown. Moreover, in vivo experimentation further confirmed the promoting effect of AP on bone formation. Conclusion. These data indicate that AP could promote MSC proliferation and osteoblast differentiation by regulating H19. Cite this article: X. Xie, M. Liu, Q. Meng. Angelica polysaccharide promotes proliferation and osteoblast differentiation of mesenchymal stem cells by regulation of long non-coding RNA H19: An animal study. Bone Joint Res 2019;8:323–332. DOI: 10.1302/2046-3758.87.BJR-2018-0223.R2

Objectives. The biomembrane (induced membrane) formed around polymethylmethacrylate (PMMA) spacers has value in clinical applications for bone defect reconstruction. Few studies have evaluated its cellular, molecular or stem cell features. Our objective was to characterise induced membrane morphology, molecular features and osteogenic stem cell characteristics. Methods. Following Institutional Review Board approval, biomembrane specimens were obtained from 12 patient surgeries for management of segmental bony defects (mean patient age 40.7 years, standard deviation 14.4). Biomembranes from nine tibias and three femurs were processed for morphologic, molecular or stem cell analyses. Gene expression was determined using the Affymetrix GeneChip Operating Software (GCOS). Molecular analyses compared biomembrane gene expression patterns with a mineralising osteoblast culture, and gene expression in specimens with longer spacer duration (> 12 weeks) with specimens with shorter durations. Statistical analyses used the unpaired student t-test (two tailed; p < 0.05 was considered significant). Results. Average PMMA spacer in vivo time was 11.9 weeks (six to 18). Trabecular bone was present in 33.3% of the biomembrane specimens; bone presence did not correlate with spacer duration. Biomembrane morphology showed high vascularity and collagen content and positive staining for the key bone forming regulators, bone morphogenetic protein 2 (BMP2) and runt-related transcription factor 2 (RUNX2). Positive differentiation of cultured biomembrane cells for osteogenesis was found in cells from patients with PMMA present for six to 17 weeks. Stem cell differentiation showed greater variability in pluripotency for osteogenic potential (70.0%) compared with chondrogenic or adipogenic potentials (100% and 90.0%, respectively). Significant upregulation of BMP2 and 6, numerous collagens, and bone gla protein was present in biomembrane compared with the cultured cell line. Biomembranes with longer resident PMMA spacer duration (vs those with shorter residence) showed significant upregulation of bone-related, stem cell, and vascular-related genes. Conclusion. The biomembrane technique is gaining favour in the management of complicated bone defects. Novel data on biological mechanisms provide improved understanding of the biomembrane’s osteogenic potential and molecular properties. Cite this article: Dr H. E. Gruber. Osteogenic, stem cell and molecular characterisation of the human induced membrane from extremity bone defects. Bone Joint Res 2016;5:106–115. DOI: 10.1302/2046-3758.54.2000483

Tapered fluted titanium stems are increasingly used for femoral revision arthroplasty. They are available in modular and non-modular forms. Modularity has advantages when the bone loss is severe, the proximal femur is mis shapen or the surgeon is unfamiliar with the implant, but it introduces the risk of fracture of the stem at the junction between it and the proximal body segment. For that reason, and while awaiting intermediate-term results of more recently introduced designs of this junction, non-modularity has attracted attention, at least for straightforward revision cases. . We review the risks and causes of fracture of tapered titanium modular revision stems and present an argument in favour of the more selective use of modular designs. Cite this article: Bone Joint J 2016;98-B(1 Suppl A):50–3

The Morscher-Spotorno (MS-30) femoral stem is a stainless-steel, straight, three-dimensionally tapered, collarless implant for cemented fixation in total hip replacement. We report the results at ten years of a consecutive series of 124 total hip replacements in 121 patients with the matt-surfaced MS-30 stem and an alumina ceramic head of 28-mm diameter. All the stems were fixed with Palacos bone cement with gentamicin using a modern cementing technique. They were combined with an uncemented, press-fit cup. The mean period of observation was 10.2 years (8.3 to 12.1) and no patient was lost to follow-up. Twenty-seven patients (22%) died with the implant in situ. Nine could only be interviewed by telephone. We included 85 patients with 88 hips in the clinical and radiological follow-up examinations. None of the stems or cups had been revised. The Harris hip score was excellent or good in 97% (85 hips) and moderate in 3% (three hips). Radiologically, six hips (6.8%) had osteolysis adjacent to the stem, mostly in Gruen zone 7. Twenty (22.7%) showed one or more radiolucent lines. Twenty-two stems (25%) had subsided by 2 mm to 5 mm. In these cases two showed osteolysis (9.1%) with subsidence and four without (6.1%). Radiolucent lines were seen in seven with migration (31.8%) and in 13 without (19.7%). No infections and no acetabular osteolysis were observed. The clinical results were excellent with survivorship after ten years of 100% and only a slightly statistically non-significant higher rate of osteolysis and radiolucency in cases of subsidence

Aims. Aseptic loosening is a major cause of failure in cemented endoprosthetic reconstructions. This paper presents the long-term outcomes of a custom-designed cross-pin fixation construct designed to minimize rotational stress and subsequent aseptic loosening in selected patients. The paper will also examine the long-term survivorship and modes of failure when using this technique. Patients and Methods. A review of 658 consecutive, prospectively collected cemented endoprosthetic reconstructions for oncological diagnoses at a single centre between 1980 and 2017 was performed. A total of 51 patients were identified with 56 endoprosthetic implants with cross-pin fixation, 21 of which were implanted following primary resection of tumour. Locations included distal femoral (n = 36), proximal femoral (n = 7), intercalary (n = 6), proximal humeral (n = 3), proximal tibial (n = 3), and distal humeral (n = 1). Results. The median follow-up was 132 months (interquartile range (IQR) 44 to 189). In all, 20 stems required revision: eight for infection, five for structural failure, five for aseptic loosening, and two for tumour progression. Mechanical survivorship at five, ten, and 15 years was 84%, 78%, and 78%, respectively. Mechanical failure rate varied by location, with no mechanical failures of proximal femoral constructs and distal femoral survivorship of 82%, 77%, and 77% at five, ten, and 15 years. The survivorship of primary constructs at five years was 74%, with no failure after 40 months, while the survivorship for revision constructs was 89%, 80%, and 80% at five, ten, and 15 years. . Conclusion. The rate of mechanical survivorship in our series is similar to those reported for other methods of reconstruction for short diaphyseal segments, such as compressive osseointegration. The mechanical failure rate differed by location, while there was no substantial difference in long-term survival between primary and revision reconstructions. Overall, custom cross-pin fixation is a viable option for endoprosthetic reconstruction of short metaphyseal segments with an acceptable rate of mechanical failure. Cite this article: Bone Joint J 2019;101-B:724–731

Objectives. As one of the heat-stable enterotoxins, Staphylococcal enterotoxin C2 (SEC2) is synthesized by Staphylococcus aureus, which has been proved to inhibit the growth of tumour cells, and is used as an antitumour agent in cancer immunotherapy. Although SEC2 has been reported to promote osteogenic differentiation of human mesenchymal stem cells (MSCs), the in vivo function of SCE2 in animal model remains elusive. The aim of this study was to further elucidate the in vivo effect of SCE2 on fracture healing. Materials and Methods. Rat MSCs were used to test the effects of SEC2 on their proliferation and osteogenic differentiation potentials. A rat femoral fracture model was used to examine the effect of local administration of SEC2 on fracture healing using radiographic analyses, micro-CT analyses, biomechanical testing, and histological analyses. Results. While SEC2 was found to have no effect on rat MSCs proliferation, it promoted the osteoblast differentiation of rat MSCs. In the rat femoral fracture model, the local administration of SEC2 accelerated fracture healing by increasing fracture callus volumes, bone volume over total volume (BV/TV), and biomechanical recovery. The SEC2 treatment group has superior histological appearance compared with the control group. Conclusion. These data suggest that local administration of SEC2 may be a novel therapeutic approach to enhancing bone repair such as fracture healing. Cite this article: T. Wu, J. Zhang, B. Wang, Y. Sun, Y. Liu, G. Li. Staphylococcal enterotoxin C2 promotes osteogenesis of mesenchymal stem cells and accelerates fracture healing. Bone Joint Res 2018;7:179–186. DOI: 10.1302/2046-3758.72.BJR-2017-0229.R1