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Bone & Joint Research
Vol. 12, Issue 11 | Pages 691 - 701
3 Nov 2023
Dai Z Chen Y He E Wang H Guo W Wu Z Huang K Zhao Q

Aims. Osteoporosis is characterized by decreased trabecular bone volume, and microarchitectural deterioration in the medullary cavity. Interleukin-19 (IL-19), a member of the IL-10 family, is an anti-inflammatory cytokine produced primarily by macrophages. The aim of our study was to investigate the effect of IL-19 on osteoporosis. Methods. Blood and femoral bone marrow suspension IL-19 levels were first measured in the lipopolysaccharide (LPS)-induced bone loss model. Small interfering RNA (siRNA) was applied to knock down IL-19 for further validation. Thereafter, osteoclast production was stimulated with IL-19 in combination with mouse macrophage colony-stimulating factor (M-CSF) and receptor activator of nuclear factor-κB ligand (RANKL). The effect of IL-19 was subsequently evaluated using tartrate-resistant acid phosphatase (TRAP) staining and quantitative real-time polymerase chain reaction (RT-qPCR). The effect of IL-19 on osteoprotegerin (OPG) was then assessed using in vitro recombinant IL-19 treatment of primary osteoblasts and MLO-Y4 osteoblast cell line. Finally, transient transfection experiments and chromatin immunoprecipitation (ChIP) experiments were used to examine the exact mechanism of action. Results. In the LPS-induced bone loss mouse model, the levels of IL-19 in peripheral blood serum and femoral bone marrow suspension were significantly increased. The in vivo results indicated that global IL-19 deletion had no significant effect on RANKL content in the serum and bone marrow, but could increase the content of OPG in serum and femoral bone marrow, suggesting that IL-19 inhibits OPG expression in bone marrow mesenchymal stem cells (BMSCs) and thus increases bone resorption. Conclusion. IL-19 promotes bone resorption by suppressing OPG expression in BMSCs in a LPS-induced bone loss mouse model, which highlights the potential benefits and side effects of IL-19 for future clinical applications. Cite this article: Bone Joint Res 2023;12(11):691–701


The Bone & Joint Journal
Vol. 106-B, Issue 10 | Pages 1100 - 1110
1 Oct 2024
Arenas-Miquelez A Barco R Cabo Cabo FJ Hachem A

Bone defects are frequently observed in anterior shoulder instability. Over the last decade, knowledge of the association of bone loss with increased failure rates of soft-tissue repair has shifted the surgical management of chronic shoulder instability. On the glenoid side, there is no controversy about the critical glenoid bone loss being 20%. However, poor outcomes have been described even with a subcritical glenoid bone defect as low as 13.5%. On the humeral side, the Hill-Sachs lesion should be evaluated concomitantly with the glenoid defect as the two sides of the same bipolar lesion which interact in the instability process, as described by the glenoid track concept. We advocate adding remplissage to every Bankart repair in patients with a Hill-Sachs lesion, regardless of the glenoid bone loss. When critical or subcritical glenoid bone loss occurs in active patients (> 15%) or bipolar off-track lesions, we should consider anterior glenoid bone reconstructions. The techniques have evolved significantly over the last two decades, moving from open procedures to arthroscopic, and from screw fixation to metal-free fixation. The new arthroscopic techniques of glenoid bone reconstruction procedures allow precise positioning of the graft, identification, and treatment of concomitant injuries with low morbidity and faster recovery. Given the problems associated with bone resorption and metal hardware protrusion, the new metal-free techniques for Latarjet or free bone block procedures seem a good solution to avoid these complications, although no long-term data are yet available. Cite this article: Bone Joint J 2024;106-B(10):1100–1110


Bone & Joint Research
Vol. 13, Issue 2 | Pages 52 - 65
1 Feb 2024
Yao C Sun J Luo W Chen H Chen T Chen C Zhang B Zhang Y

Aims. To investigate the effects of senescent osteocytes on bone homeostasis in the progress of age-related osteoporosis and explore the underlying mechanism. Methods. In a series of in vitro experiments, we used tert-Butyl hydroperoxide (TBHP) to induce senescence of MLO-Y4 cells successfully, and collected conditioned medium (CM) and senescent MLO-Y4 cell-derived exosomes, which were then applied to MC3T3-E1 cells, separately, to evaluate their effects on osteogenic differentiation. Furthermore, we identified differentially expressed microRNAs (miRNAs) between exosomes from senescent and normal MLO-Y4 cells by high-throughput RNA sequencing. Based on the key miRNAs that were discovered, the underlying mechanism by which senescent osteocytes regulate osteogenic differentiation was explored. Lastly, in the in vivo experiments, the effects of senescent MLO-Y4 cell-derived exosomes on age-related bone loss were evaluated in male SAMP6 mice, which excluded the effects of oestrogen, and the underlying mechanism was confirmed. Results. The CM and exosomes collected from senescent MLO-Y4 cells inhibited osteogenic differentiation of MC3T3-E1 cells. RNA sequencing detected significantly lower expression of miR-494-3p in senescent MLO-Y4 cell-derived exosomes compared with normal exosomes. The upregulation of exosomal miR-494-3p by miRNA mimics attenuated the effects of senescent MLO-Y4 cell-derived exosomes on osteogenic differentiation. Luciferase reporter assay demonstrated that miR-494-3p targeted phosphatase and tensin homolog (PTEN), which is a negative regulator of the phosphoinositide 3-kinase (PI3K)/AKT pathway. Overexpression of PTEN or inhibition of the PI3K/AKT pathway blocked the functions of exosomal miR-494-3p. In SAMP6 mice, senescent MLO-Y4 cell-derived exosomes accelerated bone loss, which was rescued by upregulation of exosomal miR-494-3p. Conclusion. Reduced expression of miR-494-3p in senescent osteocyte-derived exosomes inhibits osteogenic differentiation and accelerates age-related bone loss via PTEN/PI3K/AKT pathway. Cite this article: Bone Joint Res 2024;13(2):52–65


Bone & Joint Open
Vol. 5, Issue 12 | Pages 1067 - 1071
2 Dec 2024
Salzmann M Kropp E Prill R Ramadanov N Adriani M Becker R

Aims. The transepicondylar axis is a well-established reference for the determination of femoral component rotation in total knee arthroplasty (TKA). However, when severe bone loss is present in the femoral condyles, rotational alignment can be more complicated. There is a lack of validated landmarks in the supracondylar region of the distal femur. Therefore, the aim of this study was to analyze the correlation between the surgical transepicondylar axis (sTEA) and the suggested dorsal cortex line (DCL) in the coronal plane and the inter- and intraobserver reliability of its CT scan measurement. Methods. A total of 75 randomly selected CT scans were measured by three experienced surgeons independently. The DCL was defined in the coronal plane as a tangent to the dorsal femoral cortex located 75 mm above the joint line in the frontal plane. The difference between sTEA and DCL was calculated. Descriptive statistics and angulation correlations were generated for the sTEA and DCL, as well as for the distribution of measurement error for intra- and inter-rater reliability. Results. The external rotation of the DCL to the sTEA was a mean of 9.47° (SD 3.06°), and a median of 9.2° (IQR 7.45° to 11.60°), with a minimum value of 1.7° and maximum of 16.3°. The measurements of the DCL demonstrated very good to excellent test-retest and inter-rater reliability coefficients (intraclass correlation coefficient 0.80 to 0.99). Conclusion. This study reveals a correlation between the sTEA and the DCL. Overall, 10° of external rotation of the dorsal femoral cortical bone to the sTEA may serve as a reliable landmark for initial position of the femoral component. Surgeons should be aware that there are outliers in this study in up to 17% of the measurements, which potentially could result in deviations of femoral component rotation. Cite this article: Bone Jt Open 2024;5(12):1067–1071


Bone & Joint Research
Vol. 11, Issue 6 | Pages 409 - 412
22 Jun 2022
Tsang SJ Ferreira N Simpson AHRW


The Bone & Joint Journal
Vol. 106-B, Issue 5 Supple B | Pages 47 - 53
1 May 2024
Jones SA Parker J Horner M

Aims. The aims of this study were to determine the success of a reconstruction algorithm used in major acetabular bone loss, and to further define the indications for custom-made implants in major acetabular bone loss. Methods. We reviewed a consecutive series of Paprosky type III acetabular defects treated according to a reconstruction algorithm. IIIA defects were planned to use a superior augment and hemispherical acetabular component. IIIB defects were planned to receive either a hemispherical acetabular component plus augments, a cup-cage reconstruction, or a custom-made implant. We used national digital health records and registry reports to identify any reoperation or re-revision procedure and Oxford Hip Score (OHS) for patient-reported outcomes. Implant survival was determined via Kaplan-Meier analysis. Results. A total of 105 procedures were carried out in 100 patients (five bilateral) with a mean age of 73 years (42 to 94). In the IIIA defects treated, 72.0% (36 of 50) required a porous metal augment; the remaining 14 patients were treated with a hemispherical acetabular component alone. In the IIIB defects, 63.6% (35 of 55) underwent reconstruction as planned with 20 patients who actually required a hemispherical acetabular component alone. At mean follow-up of 7.6 years, survival was 94.3% (95% confidence interval 97.4 to 88.1) for all-cause revision and the overall dislocation rate was 3.8% (4 of 105). There was no difference observed in survival between type IIIA and type IIIB defects and whether a hemispherical implant alone was used for the reconstruction or not. The mean gain in OHS was 16 points. Custom-made implants were only used in six cases, in patients with either a mega-defect in which the anteroposterior diameter > 80 mm, complex pelvic discontinuity, and massive bone loss in a small pelvis. Conclusion. Our findings suggest that a reconstruction algorithm can provide a successful approach to reconstruction in major acetabular bone loss. The use of custom implants has been defined in this series and accounts for < 5% of cases. Cite this article: Bone Joint J 2024;106-B(5 Supple B):47–53


Bone & Joint Open
Vol. 3, Issue 2 | Pages 107 - 113
1 Feb 2022
Brunt ACC Gillespie M Holland G Brenkel I Walmsley P

Aims. Periprosthetic joint infection (PJI) occurs in approximately 1% to 2% of total knee arthroplasties (TKA) presenting multiple challenges, such as difficulty in diagnosis, technical complexity, and financial costs. Two-stage exchange is the gold standard for treating PJI but emerging evidence suggests 'two-in-one' single-stage revision as an alternative, delivering comparable outcomes, reduced morbidity, and cost-effectiveness. This study investigates five-year results of modified single-stage revision for treatment of PJI following TKA with bone loss. Methods. Patients were identified from prospective data on all TKA patients with PJI following the primary procedure. Inclusion criteria were: revision for PJI with bone loss requiring reconstruction, and a minimum five years’ follow-up. Patients were followed up for recurrent infection and assessment of function. Tools used to assess function were Oxford Knee Score (OKS) and American Knee Society Score (AKSS). Results. A total of 24 patients were included with a mean age of 72.7 years (SD 7.6), mean BMI of 33.3 kg/m. 2. (SD 5.7), and median ASA grade of 2 (interquartile range 2 to 4). Mean time from primary to revision was 3.0 years (10 months to 8.3 years). At revision, six patients had discharging sinus and three patients had negative cultures from tissue samples or aspirates. Two patients developed recurrence of infection: one was treated successfully with antibiotic suppression and one underwent debridement, antibiotics, and implant retention. Mean AKSS scores at two years showed significant improvement from baseline (27.1 (SD 10.2 ) vs 80.3 (SD 14.8); p < 0.001). There was no significant change in mean AKSS scores between two and five years (80.3 (SD 14.8 ) vs 74.1 (SD 19.8); p = 0.109). Five-year OKS scores were not significantly different compared to two-year scores (36.17 (SD 3.7) vs 33.0 (SD 8.5); p = 0.081). Conclusion. ‘Two-in-one’ single-stage revision is effective for treating PJI following TKA with bone loss, providing patients with sustained improvements in outcomes and infection clearance up to five years post-procedure. Cite this article: Bone Jt Open 2022;3(2):107–113


Bone & Joint Research
Vol. 11, Issue 7 | Pages 484 - 493
13 Jul 2022
Hayer S Niederreiter B Kalkgruber M Wanic K Maißner J Smolen JS Aletaha D Blüml S Redlich K

Aims. Insufficient treatment response in rheumatoid arthritis (RA) patients requires novel treatment strategies to halt disease progression. The potential benefit of combination of cytokine-inhibitors in RA is still unclear and needs further investigation. To explore the impact of combined deficiency of two major cytokines, namely interleukin (IL)-1 and IL-6, in this study double deficient mice for IL-1αβ and IL-6 were investigated in different tumour necrosis factor (TNF)-driven inflammatory bone disorders, namely peripheral arthritis and sacroiliitis, as well as systemic bone loss. Methods. Disease course, histopathological features of arthritis, and micro-CT (µCT) bone analysis of local and systemic bone loss were assessed in 15-week-old IL1-/-IL6-/-hTNFtg in comparison to IL1-/-hTNFtg, IL6-/-hTNFtg, and hTNFtg mice. µCT bone analysis of single deficient and wild-type mice was also performed. Results. Combined deficiency of IL-1/IL-6 markedly ameliorated TNF-mediated arthritis and bilateral sacroiliitis, but without additive benefits compared to single IL-1 deficiency. This finding confirms the important role of IL-1 and the marginal role of IL-6 in TNF-driven pathways of local joint damage, but questions the efficacy of potential combinatorial therapies of IL-1 and IL-6 in treatment of RA. In contrast, combined deficiency of IL-1/IL-6 led to an additive protective effect on TNF-driven systemic bone loss compared to single IL-1 and IL-6 deficiency. This finding clearly indicates a common contribution of both IL-1 and IL-6 in TNF-driven systemic bone loss, and points to a discrepancy of cytokine dependency in local and systemic TNF-driven mechanisms of inflammatory arthritis. Conclusion. Combinatorial treatments in RA might provide different benefits to inflammatory local arthritis and systemic comorbidities. Cite this article: Bone Joint Res 2022;11(7):484–493


Bone & Joint Open
Vol. 4, Issue 7 | Pages 478 - 489
1 Jul 2023
Tennent D Antonios T Arnander M Ejindu V Papadakos N Rastogi A Pearse Y

Aims. Glenoid bone loss is a significant problem in the management of shoulder instability. The threshold at which the bone loss is considered “critical” requiring bony reconstruction has steadily dropped and is now approximately 15%. This necessitates accurate measurement in order that the correct operation is performed. CT scanning is the most commonly used modality and there are a number of techniques described to measure the bone loss however few have been validated. The aim of this study was to assess the accuracy of the most commonly used techniques for measuring glenoid bone loss on CT. Methods. Anatomically accurate models with known glenoid diameter and degree of bone loss were used to determine the mathematical and statistical accuracy of six of the most commonly described techniques (relative diameter, linear ipsilateral circle of best fit (COBF), linear contralateral COBF, Pico, Sugaya, and circle line methods). The models were prepared at 13.8%, 17.6%, and 22.9% bone loss. Sequential CT scans were taken and randomized. Blinded reviewers made repeated measurements using the different techniques with a threshold for theoretical bone grafting set at 15%. Results. At 13.8%, only the Pico technique measured under the threshold. At 17.6% and 22.9% bone loss all techniques measured above the threshold. The Pico technique was 97.1% accurate, but had a high false-negative rate and poor sensitivity underestimating the need for grafting. The Sugaya technique had 100% specificity but 25% of the measurements were incorrectly above the threshold. A contralateral COBF underestimates the area by 16% and the diameter by 5 to 7%. Conclusion. No one method stands out as being truly accurate and clinicians need to be aware of the limitations of their chosen technique. They are not interchangeable, and caution must be used when reading the literature as comparisons are not reliable. Cite this article: Bone Jt Open 2023;4(7):478–489


The Bone & Joint Journal
Vol. 106-B, Issue 4 | Pages 312 - 318
1 Apr 2024
Sheth NP Jones SA Sanghavi SA Manktelow A

The advent of modular porous metal augments has ushered in a new form of treatment for acetabular bone loss. The function of an augment can be seen as reducing the size of a defect or reconstituting the anterosuperior/posteroinferior columns and/or allowing supplementary fixation. Depending on the function of the augment, the surgeon can decide on the sequence of introduction of the hemispherical shell, before or after the augment. Augments should always, however, be used with cement to form a unit with the acetabular component. Given their versatility, augments also allow the use of a hemispherical shell in a position that restores the centre of rotation and biomechanics of the hip. Progressive shedding or the appearance of metal debris is a particular finding with augments and, with other radiological signs of failure, should be recognized on serial radiographs. Mid- to long-term outcomes in studies reporting the use of augments with hemispherical shells in revision total hip arthroplasty have shown rates of survival of > 90%. However, a higher risk of failure has been reported when augments have been used for patients with chronic pelvic discontinuity. Cite this article: Bone Joint J 2024;106-B(4):312–318


Bone & Joint Research
Vol. 9, Issue 11 | Pages 827 - 839
1 Nov 2020
Hameister R Lohmann CH Dheen ST Singh G Kaur C

Aims. This study aimed to examine the effects of tumour necrosis factor-alpha (TNF-α) on osteoblasts in metal wear-induced bone loss. Methods. TNF-α immunoexpression was examined in periprosthetic tissues of patients with failed metal-on-metal hip arthroplasties and also in myeloid MM6 cells after treatment with cobalt ions. Viability and function of human osteoblast-like SaOs-2 cells treated with recombinant TNF-α were studied by immunofluorescence, terminal deoxynucleotidyl transferase-mediated dUTP nick end labelling (TUNEL) assay, western blotting, and enzyme-linked immunosorbent assay (ELISA). Results. Macrophages, lymphocytes, and endothelial cells displayed strong TNF-α immunoexpression in periprosthetic tissues containing metal wear debris. Colocalization of TNF-α with the macrophage marker CD68 and the pan-T cell marker CD3 confirmed TNF-α expression in these cells. Cobalt-treated MM6 cells secreted more TNF-α than control cells, reflecting the role of metal wear products in activating the TNF-α pathway in the myeloid cells. While TNF-α did not alter the immunoexpression of the TNF-receptor 1 (TNF-R1) in SaOs-2 cells, it increased the release of the soluble TNF-receptor 1 (sTNF-R1). There was also evidence for TNF-α-induced apoptosis. TNF-α further elicited the expression of the endoplasmic reticulum stress markers inositol-requiring enzyme (IRE)-1α, binding-immunoglobulin protein (BiP), and endoplasmic oxidoreductin1 (Ero1)-Lα. In addition, TNF-α decreased pro-collagen I α 1 secretion without diminishing its synthesis. TNF-α also induced an inflammatory response in SaOs-2 cells, as evidenced by the release of reactive oxygen and nitrogen species and the proinflammatory cytokine vascular endothelial growth factor. Conclusion. The results suggest a novel osteoblastic mechanism, which could be mediated by TNF-α and may be involved in metal wear debris-induced periprosthetic bone loss. Cite this article: Bone Joint Res 2020;9(11):827–839


The Bone & Joint Journal
Vol. 105-B, Issue 8 | Pages 888 - 894
1 Aug 2023
Murray J Jeyapalan R Davies M Sheehan C Petrie M Harrison T

Aims. Total femoral arthroplasty (TFA) is a rare procedure used in cases of significant femoral bone loss, commonly from cancer, infection, and trauma. Low patient numbers have resulted in limited published work on long-term outcomes, and even less regarding TFA undertaken for non-oncological indications. The aim of this study was to evaluate the long-term clinical outcomes of all TFAs in our unit. Methods. Data were collected retrospectively from a large tertiary referral revision arthroplasty unit’s database. Inclusion criteria included all patients who underwent TFA in our unit. Preoperative demographics, operative factors, and short- and long-term outcomes were collected for analysis. Outcome was defined using the Musculoskeletal Infection Society (MSIS) outcome reporting tool. Results. Overall, 38 TFAs were identified. The mean age was 73 years (42 to 80). All patients underwent TFA for non-oncological indications, most commonly as a consequence of infection (53%) and periprosthetic fracture (26%). The mean follow-up time was ten years (0 to 26); 63% of TFAs were considered a success based upon the MSIS outcome reporting tool. The mean time between TFA and death was 8.5 years (0.2 to 19.2), with two patients dying within one year of surgery. Within the cohort, 66% suffered at least one complication, dislocation being most common (37%); 55% of the total cohort required at least one subsequent operation. In total, 70% of TFAs undertaken for infection were considered infection-free at time of final follow-up. The percentage of mobile patients improved from 52% to 65% between pre- and postoperation, with all patients being able to at least transfer from bed to chair at time of final review. Conclusion. This study is the largest in the UK assessing the use of TFA in patients with bone loss secondary to non-oncological conditions. It demonstrates that TFA has a significant complication profile, however it is favourable in terms of mortality and rehabilitation when compared to amputation and disarticulation. Cite this article: Bone Joint J 2023;105-B(8):888–894


Bone & Joint Research
Vol. 11, Issue 7 | Pages 413 - 425
1 Jul 2022
Tu C Lai S Huang Z Cai G Zhao K Gao J Wu Z Zhong Z

Aims. Gap junction intercellular communication (GJIC) in osteocytes is impaired by oxidative stress, which is associated with age-related bone loss. Ageing is accompanied by the accumulation of advanced oxidation protein products (AOPPs). However, it is still unknown whether AOPP accumulation is involved in the impairment of osteocytes’ GJIC. This study aims to investigate the effect of AOPP accumulation on osteocytes’ GJIC in aged male mice and its mechanism. Methods. Changes in AOPP levels, expression of connexin43 (Cx43), osteocyte network, and bone mass were detected in 18-month-old and three-month-old male mice. Cx43 expression, GJIC function, mitochondria membrane potential, reactive oxygen species (ROS) levels, and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activation were detected in murine osteocyte-like cells (MLOY4 cells) treated with AOPPs. The Cx43 expression, osteocyte network, bone mass, and mechanical properties were detected in three-month-old mice treated with AOPPs for 12 weeks. Results. The AOPP levels were increased in aged mice and correlated with degeneration of osteocyte network, loss of bone mass, and decreased Cx43 expression. AOPP intervention induced NADPH oxidase activation and mitochondrial dysfunction, triggered ROS generation, reduced Cx43 expression, and ultimately impaired osteocytes’ GJIC, which were ameliorated by NADPH oxidase inhibitor apocynin, mitochondria-targeted superoxide dismutase mimetic (mito-TEMPO), and ROS scavenger N-acetyl cysteine. Chronic AOPP loading accelerated the degradation of osteocyte networks and decreased Cx43 expression, resulting in deterioration of bone mass and mechanical properties in vivo. Conclusion. Our study suggests that AOPP accumulation contributes to age-related impairment of GJIC in osteocytes of male mice, which may be part of the pathogenic mechanism responsible for bone loss during ageing. Cite this article: Bone Joint Res 2022;11(7):413–425


The Bone & Joint Journal
Vol. 104-B, Issue 9 | Pages 1039 - 1046
1 Sep 2022
Özdemir E Kuijpers MFL Visser J Schreurs BW Rijnen WHC

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


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 Open
Vol. 3, Issue 2 | Pages 114 - 122
1 Feb 2022
Green GL Arnander M Pearse E Tennent D

Aims. Recurrent dislocation is both a cause and consequence of glenoid bone loss, and the extent of the bony defect is an indicator guiding operative intervention. Literature suggests that loss greater than 25% requires glenoid reconstruction. Measuring bone loss is controversial; studies use different methods to determine this, with no clear evidence of reproducibility. A systematic review was performed to identify existing CT-based methods of quantifying glenoid bone loss and establish their reliability and reproducibility. Methods. A Preferred Reporting Items for Systematic reviews and Meta-Analyses-compliant systematic review of conventional and grey literature was performed. Results. A total of 25 studies were initially eligible. Following screening, nine papers were included for review. Main themes identified compared 2D and 3D imaging, as well as linear- compared with area-based techniques. Heterogenous data were acquired, and therefore no meta-analysis was performed. Conclusion. No ideal CT-based method is demonstrated in the current literature, however evidence suggests that surface area methods are more reproducible and lead to fewer over-estimations of bone loss, provided the views used are standardized. A prospective imaging trial is required to provide a more definitive answer to this research question. Cite this article: Bone Jt Open 2022;3(2):114–122


Bone & Joint 360
Vol. 12, Issue 3 | Pages 27 - 30
1 Jun 2023

The June 2023 Shoulder & Elbow Roundup. 360. looks at: Proximal humerus fractures: what does the literature say now?; Infection risk of steroid injections and subsequent reverse shoulder arthroplasty; Surgical versus non-surgical management of humeral shaft fractures; Core outcome set needed for elbow arthroplasty; Minimally invasive approaches to locating radial nerve in the posterior humeral approach; Predictors of bone loss in anterior glenohumeral instability; Does the addition of motor control or strengthening exercises improve rotator cuff-related shoulder pain?; Terminology and diagnostic criteria used in patients with subacromial pain syndrome


The Journal of Bone & Joint Surgery British Volume
Vol. 92-B, Issue 12 | Pages 1678 - 1684
1 Dec 2010
Mitchell SE Keating JF Robinson CM

The results of the treatment of 31 open femoral fractures (29 patients) with significant bone loss in a single trauma unit were reviewed. A protocol of early soft-tissue and bony debridement was followed by skeletal stabilisation using a locked intramedullary nail or a dynamic condylar plate for diaphyseal and metaphyseal fractures respectively. Soft-tissue closure was obtained within 48 hours then followed, if required, by elective bone grafting with or without exchange nailing. The mean time to union was 51 weeks (20 to 156). The time to union and functional outcome were largely dependent upon the location and extent of the bone loss. It was achieved more rapidly in fractures with wedge defects than in those with segmental bone loss. Fractures with metaphyseal defects healed more rapidly than those of comparable size in the diaphysis. Complications were more common in fractures with greater bone loss, and included stiffness of the knee, malunion and limb-length discrepancy. Based on our findings, we have produced an algorithm for the treatment of these injuries. We conclude that satisfactory results can be achieved in most femoral fractures with bone loss using initial debridement and skeletal stabilisation to maintain length, with further procedures as required


Bone & Joint 360
Vol. 13, Issue 5 | Pages 34 - 37
1 Oct 2024

The October 2024 Shoulder & Elbow Roundup360 looks at: Proximal humeral fractures with vascular compromise; Outcomes and challenges of revision arthroscopic rotator cuff repair: a systematic review; Evaluating treatment effectiveness for lateral elbow tendinopathy: a systematic review and network meta-analysis; Tendon transfer techniques for irreparable subscapularis tears: a comparative review; Impact of subscapularis repair in reverse shoulder arthroplasty; Isolated subscapularis tears strongly linked to shoulder pseudoparesis; Nexel and Coonrad-Morrey total elbow arthroplasties show comparable revision rates in New Zealand study; 3D MRI matches 3D CT in assessing bone loss and shoulder morphology in dislocation cases


The Bone & Joint Journal
Vol. 106-B, Issue 10 | Pages 1141 - 1149
1 Oct 2024
Saleem J Rawi B Arnander M Pearse E Tennent D

Aims. Extensive literature exists relating to the management of shoulder instability, with a more recent focus on glenoid and humeral bone loss. However, the optimal timing for surgery following a dislocation remains unclear. There is concern that recurrent dislocations may worsen subsequent surgical outcomes, with some advocating stabilization after the first dislocation. The aim of this study was to determine if the recurrence of instability following arthroscopic stabilization in patients without significant glenoid bone loss was influenced by the number of dislocations prior to surgery. Methods. A systematic review and meta-analysis was performed using the PubMed, EMBASE, Orthosearch, and Cochrane databases with the following search terms: ((shoulder or glenohumeral) and (dislocation or subluxation) and arthroscopic and (Bankart or stabilisation or stabilization) and (redislocation or re-dislocation or recurrence or instability)). Methodology followed the PRISMA guidelines. Data and outcomes were synthesized by two independent reviewers, and papers were assessed for bias and quality. Results. Overall, 35 studies including 7,995 shoulders were eligible for analysis, with a mean follow-up of 32.7 months (12 to 159.5). The rate of post-stabilization instability was 9.8% in first-time dislocators, 9.1% in recurrent dislocators, and 8.5% in a mixed cohort. A descriptive analysis investigated the influence of recurrent instability or age in the risk of instability post-stabilization, with an association seen with increasing age and a reduced risk of recurrence post-stabilization. Conclusion. Using modern arthroscopic techniques, patients sustaining an anterior shoulder dislocation without glenoid bone loss can expect a low risk of recurrence postoperatively, and no significant difference was found between first-time and recurrent dislocators. Furthermore, high-risk cohorts can expect a low, albeit slightly higher, rate of redislocation. With the findings of this study, patients and clinicians can be more informed as to the likely outcomes of arthroscopic stabilization within this patient subset. Cite this article: Bone Joint J 2024;106-B(10):1141–1149