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Bone & Joint Open
Vol. 4, Issue 1 | Pages 38 - 46
17 Jan 2023
Takami H Takegami Y Tokutake K Kurokawa H Iwata M Terasawa S Oguchi T Imagama S

Aims. The objectives of this study were to investigate the patient characteristics and mortality of Vancouver type B periprosthetic femoral fractures (PFF) subgroups divided into two groups according to femoral component stability and to compare postoperative clinical outcomes according to treatment in Vancouver type B2 and B3 fractures. Methods. A total of 126 Vancouver type B fractures were analyzed from 2010 to 2019 in 11 associated centres' database (named TRON). We divided the patients into two Vancouver type B subtypes according to implant stability. Patient demographics and functional scores were assessed in the Vancouver type B subtypes. We estimated the mortality according to various patient characteristics and clinical outcomes between the open reduction internal fixation (ORIF) and revision arthroplasty (revision) groups in patients with unstable subtype. Results. The one-year mortality rate of the stable and unstable subtype of Vancouver type B was 9.4% and 16.4%. Patient demographic factors, including residential status and pre-injury mobility were associated with mortality. There was no significant difference in mortality between patients treated with ORIF and Revision in either Vancouver B subtype. Patients treated with revision had significantly higher Parker Mobility Score (PMS) values (5.48 vs 3.43; p = 0.00461) and a significantly lower visual analogue scale (VAS) values (1.06 vs 1.94; p = 0.0399) for pain than ORIF in the unstable subtype. Conclusion. Among patients with Vancouver type B fractures, frail patients, such as those with worse scores for residential status and pre-injury mobility, had a high mortality rate. There was no significant difference in mortality between patients treated with ORIF and those treated with revision. However, in the unstable subtype, the PMS and VAS values at the final follow-up examination were significantly better in patients who received revision. Based on postoperative activities of daily life, we therefore recommend evision in instances when either treatment option is feasible. Cite this article: Bone Jt Open 2023;4(1):38–46


Bone & Joint Research
Vol. 10, Issue 9 | Pages 619 - 628
27 Sep 2021
Maestro-Paramio L García-Rey E Bensiamar F Saldaña L

Aims. To investigate whether idiopathic osteonecrosis of the femoral head (ONFH) is related to impaired osteoblast activities. Methods. We cultured osteoblasts isolated from trabecular bone explants taken from the femoral head and the intertrochanteric region of patients with idiopathic ONFH, or from the intertrochanteric region of patients with osteoarthritis (OA), and compared their viability, mineralization capacity, and secretion of paracrine factors. Results. Osteoblasts from the intertrochanteric region of patients with ONFH showed lower alkaline phosphatase (ALP) activity and mineralization capacity than osteoblasts from the same skeletal site in age-matched patients with OA, as well as lower messenger RNA (mRNA) levels of genes encoding osteocalcin and bone sialoprotein and higher osteopontin expression. In addition, osteoblasts from patients with ONFH secreted lower osteoprotegerin (OPG) levels than those from patients with OA, resulting in a higher receptor activator of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) ligand (RANKL)-to-OPG ratio. In patients with ONFH, osteoblasts from the femoral head showed reduced viability and mineralized nodule formation compared with osteoblasts from the intertrochanteric region. Notably, the secretion of the pro-resorptive factors interleukin-6 and prostaglandin E. 2. as well as the RANKL-to-OPG ratio were markedly higher in osteoblast cultures from the femoral head than in those from the intertrochanteric region. Conclusion. Idiopathic ONFH is associated with a reduced mineralization capacity of osteoblasts and increased secretion of pro-resorptive factors. Cite this article: Bone Joint Res 2021;10(9):619–628


Bone & Joint Research
Vol. 10, Issue 9 | Pages 611 - 618
27 Sep 2021
Ali E Birch M Hopper N Rushton N McCaskie AW Brooks RA

Aims. Accumulated evidence indicates that local cell origins may ingrain differences in the phenotypic activity of human osteoblasts. We hypothesized that these differences may also exist in osteoblasts harvested from the same bone type at periarticular sites, including those adjacent to the fixation sites for total joint implant components. Methods. Human osteoblasts were obtained from the acetabulum and femoral neck of seven patients undergoing total hip arthroplasty (THA) and from the femoral and tibial cuts of six patients undergoing total knee arthroplasty (TKA). Osteoblasts were extracted from the usually discarded bone via enzyme digestion, characterized by flow cytometry, and cultured to passage three before measurement of metabolic activity, collagen production, alkaline phosphatase (ALP) expression, and mineralization. Results. Osteoblasts from the acetabulum showed lower proliferation (p = 0.034), cumulative collagen release (p < 0.001), and ALP expression (p = 0.009), and produced less mineral (p = 0.006) than those from the femoral neck. Osteoblasts from the tibia produced significantly less collagen (p = 0.021) and showed lower ALP expression than those from the distal femur. Conclusion. We have demonstrated for the first time an anatomical regional variation in the biological behaviours of osteoblasts on either side of the hip and knee joint. The lower osteoblast proliferation, matrix production, and mineralization from the acetabulum compared to those from the proximal femur may be reflected in differences in bone formation and implant fixation at these sites. Cite this article: Bone Joint Res 2021;10(9):611–618


Aims. Treatment outcomes for methicillin-resistant Staphylococcus aureus (MRSA) periprosthetic joint infection (PJI) using systemic vancomycin and antibacterial cement spacers during two-stage revision arthroplasty remain unsatisfactory. This study explored the efficacy and safety of intra-articular vancomycin injections for PJI control after debridement and cement spacer implantation in a rat model. Methods. Total knee arthroplasty (TKA), MRSA inoculation, debridement, and vancomycin-spacer implantation were performed successively in rats to mimic first-stage PJI during the two-stage revision arthroplasty procedure. Vancomycin was administered intraperitoneally or intra-articularly for two weeks to control the infection after debridement and spacer implantation. Results. Rats receiving intra-articular vancomycin showed the best outcomes among the four treatment groups, with negative bacterial cultures, increased weight gain, increased capacity for weightbearing activities, increased residual bone volume preservation, and reduced inflammatory reactions in the joint tissues, indicating MRSA eradication in the knee. The vancomycin-spacer and/or systemic vancomycin failed to eliminate the MRSA infections following a two-week antibiotic course. Serum vancomycin levels did not reach nephrotoxic levels in any group. Mild renal histopathological changes, without changes in serum creatinine levels, were observed in the intraperitoneal vancomycin group compared with the intra-articular vancomycin group, but no changes in hepatic structure or serum alanine aminotransferase or aspartate aminotransferase levels were observed. No local complications were observed, such as sinus tract or non-healing surgical incisions. Conclusion. Intra-articular vancomycin injection was effective and safe for PJI control following debridement and spacer implantation in a rat model during two-stage revision arthroplasties, with better outcomes than systemic vancomycin administration. Cite this article: Bone Joint Res 2022;11(6):371–385


Bone & Joint Open
Vol. 3, Issue 6 | Pages 448 - 454
6 Jun 2022
Korup LR Larsen P Nanthan KR Arildsen M Warming N Sørensen S Rahbek O Elsoe R

Aims. The aim of this study was to report a complete overview of both incidence, fracture distribution, mode of injury, and patient baseline demographics of paediatric distal forearm fractures to identify age of risk and types of activities leading to injury. Methods. Population-based cohort study with manual review of radiographs and charts. The primary outcome measure was incidence of paediatric distal forearm fractures. The study was based on an average at-risk population of 116,950. A total number of 4,316 patients sustained a distal forearm fracture in the study period. Females accounted for 1,910 of the fractures (44%) and males accounted for 2,406 (56%). Results. The overall incidence of paediatric distal forearm fractures was 738.1/100,000 persons/year (95% confidence interval (CI) 706/100,000 to 770/100,000). Female incidences peaked with an incidence of 1,578.3/100,000 persons/year at age ten years. Male incidence peaked at age 13 years, with an incidence of 1,704.3/100,000 persons/year. The most common fracture type was a greenstick fracture to the radius (48%), and the most common modes of injury were sports and falls from ≤ 1 m. A small year-to-year variation was reported during the five-year study period, but without any trends. Conclusion. Results show that paediatric distal forearm fractures are very common throughout childhood in both sexes, with almost 2% of males aged 13 years sustaining a forearm fracture each year. Cite this article: Bone Jt Open 2022;3(6):448–454


The Bone & Joint Journal
Vol. 104-B, Issue 8 | Pages 972 - 979
1 Aug 2022
Richardson C Bretherton CP Raza M Zargaran A Eardley WGP Trompeter AJ

Aims. The purpose of this study was to determine the weightbearing practice of operatively managed fragility fractures in the setting of publically funded health services in the UK and Ireland. Methods. The Fragility Fracture Postoperative Mobilisation (FFPOM) multicentre audit included all patients aged 60 years and older undergoing surgery for a fragility fracture of the lower limb between 1 January 2019 and 30 June 2019, and 1 February 2021 and 14 March 2021. Fractures arising from high-energy transfer trauma, patients with multiple injuries, and those associated with metastatic deposits or infection were excluded. We analyzed this patient cohort to determine adherence to the British Orthopaedic Association Standard, “all surgery in the frail patient should be performed to allow full weight-bearing for activities required for daily living”. Results. A total of 19,557 patients (mean age 82 years (SD 9), 16,241 having a hip fracture) were included. Overall, 16,614 patients (85.0%) were instructed to perform weightbearing where required for daily living immediately postoperatively (15,543 (95.7%) hip fracture and 1,071 (32.3%) non-hip fracture patients). The median length of stay was 12.2 days (interquartile range (IQR) 7.9 to 20.0) (12.6 days (IQR 8.2 to 20.4) for hip fracture and 10.3 days (IQR 5.5 to 18.7) for non-hip fracture patients). Conclusion. Non-hip fracture patients experienced more postoperative weightbearing restrictions, although they had a shorter hospital stay. Patients sustaining fractures of the shaft and distal femur had a longer median length of stay than demographically similar patients who received hip fracture surgery. We have shown a significant disparity in weightbearing restrictions placed on patients with fragility fractures, despite the publication of a national guideline. Surgeons intentionally restrict postoperative weightbearing in the majority of non-hip fractures, yet are content with unrestricted weightbearing following operations for hip fractures. Cite this article: Bone Joint J 2022;104-B(8):972–979


Bone & Joint Research
Vol. 11, Issue 5 | Pages 304 - 316
17 May 2022
Kim MH Choi LY Chung JY Kim E Yang WM

Aims. The association of auraptene (AUR), a 7-geranyloxycoumarin, on osteoporosis and its potential pathway was predicted by network pharmacology and confirmed in experimental osteoporotic mice. Methods. The network of AUR was constructed and a potential pathway predicted by Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and Gene Ontology (GO) terms enrichment. Female ovariectomized (OVX) Institute of Cancer Research mice were intraperitoneally injected with 0.01, 0.1, and 1 mM AUR for four weeks. The bone mineral density (BMD) level was measured by dual-energy X-ray absorptiometry. The bone microstructure was determined by histomorphological changes in the femora. In addition, biochemical analysis of the serum and assessment of the messenger RNA (mRNA) levels of osteoclastic markers were performed. Results. In total, 65.93% of the genes of the AUR network matched with osteoporosis-related genes. Osteoclast differentiation was predicted to be a potential pathway of AUR in osteoporosis. Based on the network pharmacology, the BMD and bone mineral content levels were significantly (p < 0.05) increased in the whole body, femur, tibia, and lumbar spine by AUR. AUR normalized the bone microstructure and the serum alkaline phosphatase (ALP), bone-specific alkaline phosphatase (bALP), osteocalcin, and calcium in comparison with the OVX group. In addition, AUR treatment reduced TRAP-positive osteoclasts and receptor activator of nuclear factor kappa-B ligand (RANKL). +. nuclear factor of activated T cells 1 (NFATc1). +. expression in the femoral body. Moreover, the expressions of initiators for osteoclastic resorption and bone matrix degradation were significantly (p < 0.05) regulated by AUR in the lumbar spine of the osteoporotic mice. Conclusion. AUR ameliorated bone loss by downregulating the RANKL/NFATc1 pathway, resulting in improvement of osteoporosis. In conclusion, AUR might be an ameliorative cure that alleviates bone loss in osteoporosis via inhibition of osteoclastic activity. Cite this article: Bone Joint Res 2022;11(5):304–316


Bone & Joint Research
Vol. 11, Issue 5 | Pages 317 - 326
23 May 2022
Edwards TC Guest B Garner A Logishetty K Liddle AD Cobb JP

Aims. This study investigates the use of the metabolic equivalent of task (MET) score in a young hip arthroplasty population, and its ability to capture additional benefit beyond the ceiling effect of conventional patient-reported outcome measures. Methods. From our electronic database of 751 hip arthroplasty procedures, 221 patients were included. Patients were excluded if they had revision surgery, an alternative hip procedure, or incomplete data either preoperatively or at one-year follow-up. Included patients had a mean age of 59.4 years (SD 11.3) and 54.3% were male, incorporating 117 primary total hip and 104 hip resurfacing arthroplasty operations. Oxford Hip Score (OHS), EuroQol five-dimension questionnaire (EQ-5D), and the MET were recorded preoperatively and at one-year follow-up. The distribution was examined reporting the presence of ceiling and floor effects. Validity was assessed correlating the MET with the other scores using Spearman’s rank correlation coefficient and determining responsiveness. A subgroup of 93 patients scoring 48/48 on the OHS were analyzed by age, sex, BMI, and preoperative MET using the other metrics to determine if differences could be established despite scoring identically on the OHS. Results. Postoperatively the OHS and EQ-5D demonstrate considerable negatively skewed distributions with ceiling effects of 41.6% and 53.8%, respectively. The MET was normally distributed postoperatively with no relevant ceiling effect. Weak-to-moderate significant correlations were found between the MET and the other two metrics. In the 48/48 subgroup, no differences were found comparing groups with the EQ-5D, however significantly higher mean MET scores were demonstrated for patients aged < 60 years (12.7 (SD 4.7) vs 10.6 (SD 2.4), p = 0.008), male patients (12.5 (SD 4.5) vs 10.8 (SD 2.8), p = 0.024), and those with preoperative MET scores > 6 (12.6 (SD 4.2) vs 11.0 (SD 3.3), p = 0.040). Conclusion. The MET is normally distributed in patients following hip arthroplasty, recording levels of activity which are undetectable using the OHS. Cite this article: Bone Joint Res 2022;11(5):317–326


Bone & Joint Research
Vol. 10, Issue 1 | Pages 1 - 9
1 Jan 2021
Garner A Dandridge O Amis AA Cobb JP van Arkel RJ

Aims. Unicompartmental knee arthroplasty (UKA) and bicompartmental knee arthroplasty (BCA) have been associated with improved functional outcomes compared to total knee arthroplasty (TKA) in suitable patients, although the reason is poorly understood. The aim of this study was to measure how the different arthroplasties affect knee extensor function. Methods. Extensor function was measured for 16 cadaveric knees and then retested following the different arthroplasties. Eight knees underwent medial UKA then BCA, then posterior-cruciate retaining TKA, and eight underwent the lateral equivalents then TKA. Extensor efficiency was calculated for ranges of knee flexion associated with common activities of daily living. Data were analyzed with repeated measures analysis of variance (α = 0.05). Results. Compared to native, there were no reductions in either extension moment or efficiency following UKA. Conversion to BCA resulted in a small decrease in extension moment between 70° and 90° flexion (p < 0.05), but when examined in the context of daily activity ranges of flexion, extensor efficiency was largely unaffected. Following TKA, large decreases in extension moment were measured at low knee flexion angles (p < 0.05), resulting in 12% to 43% reductions in extensor efficiency for the daily activity ranges. Conclusion. This cadaveric study found that TKA resulted in inferior extensor function compared to UKA and BCA. This may, in part, help explain the reported differences in function and satisfaction differences between partial and total knee arthroplasty. Cite this article: Bone Joint Res 2021;10(1):1–9


Bone & Joint Open
Vol. 3, Issue 5 | Pages 404 - 414
9 May 2022
McGuire MF Vakulenko-Lagun B Millis MB Almakias R Cole EP Kim HKW

Aims. Perthes’ disease is an uncommon hip disorder with limited data on the long-term outcomes in adulthood. We partnered with community-based foundations and utilized web-based survey methodology to develop the Adult Perthes Survey, which includes demographics, childhood and adult Perthes’ disease history, the University of California Los Angeles (UCLA) Activity Scale item, Short Form-36, the Hip disability and Osteoarthritis Outcome Score, and a body pain diagram. Here we investigate the following questions: 1) what is the feasibility of obtaining > 1,000 survey responses from adults who had Perthes’ disease using a web-based platform?; and 2) what are the baseline characteristics and demographic composition of our sample?. Methods. The survey link was available publicly for 15 months and advertised among support groups. Of 1,505 participants who attempted the Adult Perthes survey, 1,182 completed it with a median timeframe of 11 minutes (IQR 8.633 to 14.72). Participants who dropped out were similar to those who completed the survey on several fixed variables. Participants represented 45 countries including the USA (n = 570; 48%), UK (n = 295; 25%), Australia (n = 133; 11%), and Canada (n = 46; 4%). Of the 1,182 respondents, 58% were female and the mean age was 39 years (SD 12.6). Results. Ages at onset of Perthes’ disease were < six years (n = 512; 43%), six to seven years (n = 321; 27%), eight to 11 years (n = 261; 22%), and > 11 years (n = 76; 6%), similar to the known age distribution of Perthes’ disease. During childhood, 40% (n = 476) of respondents had at least one surgery. Bracing, weightbearing restriction, and absence of any treatment varied significantly between USA and non-USA respondents (p < 0.001, p = 0.002, and p < 0.001, respectively). As adults, 22% (n = 261) had at least one total hip arthroplasty, and 30% (n = 347) had any type of surgery; both more commonly reported among women (p = 0.002). Conclusion. While there are limitations due to self-sampling, our study shows the feasibility of obtaining a large set of patient-reported data from adults who had childhood Perthes’ from multiple countries. Cite this article: Bone Jt Open 2022;3(5):404–414


Aims. The aim of this study was to assess and compare active rotation of the forearm in normal subjects after the application of a short-arm cast (SAC) in the semisupination position and a long-arm cast (LAC) in the neutral position. A clinical study was also conducted to compare the functional outcomes of using a SAC in the semisupination position with those of using a LAC in the neutral position in patients who underwent arthroscopic triangular fibrocartilage complex (TFCC) foveal repair. Methods. A total of 40 healthy right-handed volunteers were recruited. Active pronation and supination of the forearm were measured in each subject using a goniometer. In the retrospective clinical study, 40 patients who underwent arthroscopic foveal repair were included. The wrist was immobilized postoperatively using a SAC in the semisupination position (approximately 45°) in 16 patients and a LAC in 24. Clinical outcomes were assessed using grip strength and patient-reported outcomes. The degree of disability caused by cast immobilization was also evaluated when the cast was removed. Results. Supination was significantly more restricted with LACs than with SACs in the semisupination position in male and female patients (p < 0.001 for both). However, pronation was significantly more restricted with SACs in the semisupination position than with LACs in female patients (p = 0.003) and was not significantly different in male patients (p = 0.090). In the clinical study, both groups showed improvement in all parameters with significant differences in grip strength, visual analogue scale scores for pain, modified Mayo Wrist Score, the Disability of the Arm, Shoulder, and Hand (DASH) score, and the Patient-Rated Wrist Evaluation (PRWE) score. No significant postoperative differences were noted between LACs and SACs in the semisupination position. However, the disability caused by immobilization in a cast was significantly higher in patients who had a LAC on the dominant hand (p < 0.001). Conclusion. We found that a SAC in the semisupination position is as effective as a LAC in restricting pronation of the forearm. In addition, postoperative immobilization with a SAC in the semisupination position resulted in comparable pain scores and functional outcomes to immobilization with a LAC after TFCC foveal repair, with less restriction of daily activities. Therefore, we recommend that surgeons consider using a SAC in the semisupination position for postoperative immobilization following TFCC foveal repair for dorsal instability of the distal radioulnar joint. Cite this article: Bone Joint J 2022;104-B(2):249–256


Aims. Proliferation, migration, and differentiation of anterior cruciate ligament (ACL) remnant and surrounding cells are fundamental processes for ACL reconstruction; however, the interaction between ACL remnant and surrounding cells is unclear. We hypothesized that ACL remnant cells preserve the capability to regulate the surrounding cells’ activity, collagen gene expression, and tenogenic differentiation. Moreover, extracorporeal shock wave (ESW) would not only promote activity of ACL remnant cells, but also enhance their paracrine regulation of surrounding cells. Methods. Cell viability, proliferation, migration, and expression levels of Collagen-I (COL-I) A1, transforming growth factor beta (TGF-β), and vascular endothelial growth factor (VEGF) were compared between ACL remnant cells untreated and treated with ESW (0.15 mJ/mm. 2. , 1,000 impulses, 4 Hz). To evaluate the subsequent effects on the surrounding cells, bone marrow stromal cells (BMSCs)’ viability, proliferation, migration, and levels of Type I Collagen, Type III Collagen, and tenogenic gene (Scx, TNC) expression were investigated using coculture system. Results. ESW-treated ACL remnant cells presented higher cell viability, proliferation, migration, and increased expression of COL-I A1, TGF-β, and VEGF. BMSC proliferation and migration rate significantly increased after coculture with ACL remnant cells with and without ESW stimulation compared to the BMSCs alone group. Furthermore, ESW significantly enhanced ACL remnant cells’ capability to upregulate the collagen gene expression and tenogenic differentiation of BMSCs, without affecting cell viability, TGF-β, and VEGF expression. Conclusion. ACL remnant cells modulated activity and differentiation of surrounding cells. The results indicated that ESW enhanced ACL remnant cells viability, proliferation, migration, and expression of collagen, TGF-β, VEGF, and paracrine regulation of BMSC proliferation, migration, collagen expression, and tenogenesis. Cite this article: Bone Joint Res 2020;9(8):457–467


Bone & Joint Research
Vol. 9, Issue 7 | Pages 412 - 420
1 Jul 2020
Hefka Blahnova V Dankova J Rampichova M Filova E

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


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


The Bone & Joint Journal
Vol. 102-B, Issue 8 | Pages 1033 - 1040
1 Aug 2020
Kennedy JA Mohammad HR Yang I Mellon SJ Dodd CAF Pandit HG Murray DW

Aims. To report mid- to long-term results of Oxford mobile bearing domed lateral unicompartmental knee arthroplasty (UKA), and determine the effect of potential contraindications on outcome. Methods. A total of 325 consecutive domed lateral UKAs undertaken for the recommended indications were included, and their functional and survival outcomes were assessed. The effects of age, weight, activity, and the presence of full-thickness erosions of cartilage in the patellofemoral joint on outcome were evaluated. Results. Median follow-up was seven years (3 to 14), and mean age at surgery was 65 years (39 to 90). Median Oxford Knee Score (OKS) was 43 (interquartile range (IQR) 37 to 47), with 260 (80%) achieving a good or excellent score (OKS > 34). Revisions occurred in 34 (10%); 14 (4%) were for dislocation, of which 12 had no recurrence following insertion of a new bearing, and 12 (4%) were revised for medial osteoarthritis (OA). Ten-year survival was 85% (95% confidence interval (CI) 79 to 90, at risk 72). Age, weight, activity, and patellofemoral erosions did not have a significant effect on the clinical outcome or survival. Conclusion. Domed lateral UKA provides a good alternative to total knee arthroplasty (TKA) in the management of lateral compartment OA. Although dislocation is relatively easy to treat successfully, the dislocation rate of 4% is high. It is recommended that the stability of the bearing is assessed intraoperatively. If the bearing can easily be displaced, the fixed rather than the mobile bearing version of the Oxford lateral tibial component should be inserted instead. Younger age, heavier weight, high activity, and patellofemoral erosions did not detrimentally affect outcome, so should not be considered contraindications. Cite this article: Bone Joint J 2020;102-B(8):1033–1040


Bone & Joint Open
Vol. 3, Issue 4 | Pages 307 - 313
7 Apr 2022
Singh V Bieganowski T Huang S Karia R Davidovitch RI Schwarzkopf R

Aims. The Forgotten Joint Score-12 (FJS-12) is a validated patient-reported outcome measure (PROM) tool designed to assess artificial prosthesis awareness during daily activities following total hip arthroplasty (THA). The patient-acceptable symptom state (PASS) is the minimum cut-off value that corresponds to a patient’s satisfactory state-of-health. Despite the validity and reliability of the FJS-12 having been previously demonstrated, the PASS has yet to be clearly defined. This study aims to define the PASS of the FJS-12 following primary THA. Methods. We retrospectively reviewed all patients who underwent primary elective THA from 2019 to 2020, and answered both the FJS-12 and the Hip Disability and Osteoarthritis Outcome Score, Joint Replacement (HOOS, JR) questionnaires one-year postoperatively. HOOS, JR score was used as the anchor to estimate the PASS of FJS-12. Two statistical methods were employed: the receiver operating characteristic (ROC) curve point, which maximized the Youden index; and 75th percentile of the cumulative percentage curve of patients who had the HOOS, JR score difference larger than the cut-off value. Results. This study included 780 patients. The mean one-year FJS-12 score was 65.42 (SD 28.59). The mean one-year HOOS, JR score was 82.70 (SD 16.57). A high positive correlation between FJS-12 and HOOS, JR was found (r = 0.74; p<0.001), making the HOOS, JR a valid external anchor. The threshold score of the FJS-12 that maximized the sensitivity and specificity for detecting a PASS was 66.68 (area under the curve = 0.8). The cut-off score value computed with the 75th percentile approach was 92.20. Conclusion. The PASS threshold for the FJS-12 at one year following primary THA was 66.68 and 92.20 using the ROC curve and 75th percentile approaches, respectively. These values can be used to achieve consensus about meaningful postoperative improvement to maximize the utility of the FJS-12 to evaluate and counsel patients undergoing THA. Cite this article: Bone Jt Open 2022;3(4):307–313


Bone & Joint Open
Vol. 2, Issue 12 | Pages 1089 - 1095
21 Dec 2021
Luo W Ali MS Limb R Cornforth C Perry DC

Aims. The Patient-Reported Outcomes Measurement Information System (PROMIS) has demonstrated faster administration, lower burden of data capture and reduced floor and ceiling effects compared to traditional Patient Reported Outcomes Measurements (PROMs). We investigated the suitability of PROMIS Mobility score in assessing physical function in the sequelae of childhood hip disease. Methods. In all, 266 adolscents (aged ≥ 12 years) and adults were identified with a prior diagnosis of childhood hip disease (either Perthes’ disease (n = 232 (87.2%)) or Slipped Capital Femoral Epiphysis (n = 34 (12.8%)) with a mean age of 27.73 years (SD 12.24). Participants completed the PROMIS Mobility Computer Adaptive Test, the Non-Arthritic Hip Score (NAHS), EuroQol five-dimension five-level questionnaire, and the Numeric Pain Rating Scale. We investigated the correlation between the PROMIS Mobility and other tools to assess use in this population and any clustering of outcome scores. Results. There was a strong correlation between the PROMIS Mobility and other established PROMs; NAHS (rs = 0.79; p < 0.001). There was notable clustering in PROMIS at the upper end of the distribution score (42.5%), with less seen in the NAHS (20.3%). However, the clustering was broadly similar between PROMIS Mobility and the comparable domains of the NAHS; function (53.6%), and activity (35.0%). Conclusion. PROMIS Mobility strongly correlated with other tools demonstrating convergent construct validity. There was clustering of physical function scores at the upper end of the distributions, which may reflect truncation of the data caused by participants having excellent outcomes. There were elements of disease not captured within PROMIS Mobility alone, and difficulties in differentiating those with the highest levels of function. Cite this article: Bone Jt Open 2021;2(12):1089–1095


Bone & Joint Open
Vol. 1, Issue 2 | Pages 8 - 12
18 Feb 2020
Bhimani SJ Bhimani R Smith A Eccles C Smith L Malkani A

Aims. Robotic-assisted total knee arthroplasty (RA-TKA) has been introduced to provide accurate bone cuts and help achieve the target knee alignment, along with symmetric gap balancing. The purpose of this study was to determine if any early clinical benefits could be realized following TKA using robotic-assisted technology. Methods. In all, 140 consecutive patients undergoing RA-TKA and 127 consecutive patients undergoing conventional TKA with minimum six-week follow-up were reviewed. Differences in visual analogue scores (VAS) for pain at rest and with activity, postoperative opiate usage, and length of stay (LOS) between the RA-TKA and conventional TKA groups were compared. Results. Patients undergoing RA-TKA had lower average VAS pain scores at rest (p = 0.001) and with activity (p = 0.03) at two weeks following the index procedure. At the six-week interval, the RA-TKA group had lower VAS pain scores with rest (p = 0.03) and with activity (p = 0.02), and required 3.2 mg less morphine equivalents per day relative to the conventional group (p < 0.001). At six weeks, a significantly greater number of patients in the RA-TKA group were free of opioid use compared to the conventional TKA group; 70.7% vs 57.0% (p = 0.02). Patients in the RA-TKA group had a shorter LOS; 1.9 days versus 2.3 days (p < 0.001), and also had a greater percentage of patient discharged on postoperative day one; 41.3% vs 20.5% (p < 0.001). Conclusion. Patients undergoing RA-TKA had lower pain levels at both rest and with activity, required less opioid medication, and had a shorter LOS


Bone & Joint Research
Vol. 10, Issue 11 | Pages 714 - 722
1 Nov 2021
Qi W Feng X Zhang T Wu H Fang C Leung F

Aims. To fully verify the reliability and reproducibility of an experimental method in generating standardized micromotion for the rat femur fracture model. Methods. A modularized experimental device has been developed that allows rat models to be used instead of large animal models, with the aim of reducing systematic errors and time and money constraints on grouping. The bench test was used to determine the difference between the measured and set values of the micromotion produced by this device under different simulated loading weights. The displacement of the fixator under different loading conditions was measured by compression tests, which was used to simulate the unexpected micromotion caused by the rat’s ambulation. In vivo preliminary experiments with a small sample size were used to test the feasibility and effectiveness of the whole experimental scheme and surgical scheme. Results. The bench test showed that a weight loading < 500 g did not affect the operation of experimental device. The compression test demonstrated that the stiffness of the device was sufficient to keep the uncontrollable motion between fracture ends, resulting from the rat’s daily activities, within 1% strain. In vivo results on 15 rats prove that the device works reliably, without overburdening the experimental animals, and provides standardized micromotion reproductively at the fracture site according to the set parameters. Conclusion. Our device was able to investigate the effect of micromotion parameters on fracture healing by generating standardized micromotion to small animal models. Cite this article: Bone Joint Res 2021;10(11):714–722


The Bone & Joint Journal
Vol. 102-B, Issue 1 | Pages 55 - 63
1 Jan 2020
Hagberg K Ghassemi Jahani S Kulbacka-Ortiz K Thomsen P Malchau H Reinholdt C

Aims. The aim of this study was to describe implant and patient-reported outcome in patients with a unilateral transfemoral amputation (TFA) treated with a bone-anchored, transcutaneous prosthesis. Methods. In this cohort study, all patients with a unilateral TFA treated with the Osseointegrated Prostheses for the Rehabilitation of Amputees (OPRA) implant system in Sahlgrenska University Hospital, Gothenburg, Sweden, between January 1999 and December 2017 were included. The cohort comprised 111 patients (78 male (70%)), with a mean age 45 years (17 to 70). The main reason for amputation was trauma in 75 (68%) and tumours in 23 (21%). Patients answered the Questionnaire for Persons with Transfemoral Amputation (Q-TFA) before treatment and at two, five, seven, ten, and 15 years’ follow-up. A prosthetic activity grade was assigned to each patient at each timepoint. All mechanical complications, defined as fracture, bending, or wear to any part of the implant system resulting in removal or change, were recorded. Results. The Q-TFA scores at two, five, seven, and ten years showed significantly more prosthetic use, better mobility, fewer problems, and an improved global situation, compared with baseline. The survival rate of the osseointegrated implant part (the fixture) was 89% and 72% after seven and 15 years, respectively. A total of 61 patients (55%) had mechanical complications (mean 3.3 (SD 5.76)), resulting in exchange of the percutaneous implant parts. There was a positive relationship between a higher activity grade and the number of mechanical complications. Conclusion. Compared with before treatment, the patient-reported outcome was significantly better and remained so over time. Although osseointegration and the ability to transfer loads over a 15-year period have been demonstrated, a large number of mechanical failures in the external implant parts were found. Since these were related to higher activity, restrictions in activity and improvements to the mechanical properties of the implant system are required. Cite this article: Bone Joint J 2020;102-B(1):55–63