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Bone & Joint Research
Vol. 6, Issue 1 | Pages 14 - 21
1 Jan 2017
Osagie-Clouard L Sanghani A Coathup M Briggs T Bostrom M Blunn G

Intermittently administered parathyroid hormone (PTH 1-34) has been shown to promote bone formation in both human and animal studies. The hormone and its analogues stimulate both bone formation and resorption, and as such at low doses are now in clinical use for the treatment of severe osteoporosis. By varying the duration of exposure, parathyroid hormone can modulate genes leading to increased bone formation within a so-called ‘anabolic window’. The osteogenic mechanisms involved are multiple, affecting the stimulation of osteoprogenitor cells, osteoblasts, osteocytes and the stem cell niche, and ultimately leading to increased osteoblast activation, reduced osteoblast apoptosis, upregulation of Wnt/β-catenin signalling, increased stem cell mobilisation, and mediation of the RANKL/OPG pathway. Ongoing investigation into their effect on bone formation through ‘coupled’ and ‘uncoupled’ mechanisms further underlines the impact of intermittent PTH on both cortical and cancellous bone. Given the principally catabolic actions of continuous PTH, this article reviews the skeletal actions of intermittent PTH 1-34 and the mechanisms underlying its effect. Cite this article: L. Osagie-Clouard, A. Sanghani, M. Coathup, T. Briggs, M. Bostrom, G. Blunn. Parathyroid hormone 1-34 and skeletal anabolic action: The use of parathyroid hormone in bone formation. Bone Joint Res 2017;6:14–21. DOI: 10.1302/2046-3758.61.BJR-2016-0085.R1


Bone & Joint Open
Vol. 2, Issue 1 | Pages 40 - 47
1 Jan 2021
Kivle K Lindland ES Mjaaland KE Svenningsen S Nordsletten L

Aims

The gluteus minimus (GMin) and gluteus medius (GMed) have unique structural and functional segments that may be affected to varying degrees, by end-stage osteoarthritis (OA) and normal ageing. We used data from patients with end-stage OA and matched healthy controls to 1) quantify the atrophy of the GMin and GMed in the two groups and 2) describe the distinct patterns of the fatty infiltration in the different segments of the GMin and GMed in the two groups.

Methods

A total of 39 patients with end-stage OA and 12 age- and sex frequency-matched healthy controls were prospectively enrolled in the study. Fatty infiltration within the different segments of the GMin and the GMed was assessed on MRI according to the semiquantitative classification system of Goutallier and normalized cross-sectional areas were measured.


Bone & Joint Research
Vol. 6, Issue 5 | Pages 277 - 283
1 May 2017
Yoshikawa M Nakasa T Ishikawa M Adachi N Ochi M

Objectives. Regenerative medicine is an emerging field aimed at the repair and regeneration of various tissues. To this end, cytokines (CKs), growth factors (GFs), and stem/progenitor cells have been applied in this field. However, obtaining and preparing these candidates requires invasive, costly, and time-consuming procedures. We hypothesised that skeletal muscle could be a favorable candidate tissue for the concept of a point-of-care approach. The purpose of this study was to characterize and confirm the biological potential of skeletal muscle supernatant for use in regenerative medicine. Methods. Semitendinosus muscle was used after harvesting tendon from patients who underwent anterior cruciate ligament reconstructions. A total of 500 milligrams of stripped muscle was minced and mixed with 1 mL of saline. The collected supernatant was analysed by enzyme-linked immunosorbent assay (ELISA) and flow cytometry. The biological effects of the supernatant on cell proliferation, osteogenesis, and angiogenesis in vitro were evaluated using human mesenchymal stem cells (hMSCs) and human umbilical cord vein endothelial cells (HUVECs). Results. The supernatant contained several GFs/CKs, with especially high levels of basic fibroblast growth factor, and CD34+ cells as the stem/progenitor cell fraction. With regard to biological potential, we confirmed that cell proliferation, osteoinduction, and angiogenesis in hMSCs and HUVECs were enhanced by the supernatant. Conclusions. The current study demonstrates the potential of a new point-of-care strategy for regenerative medicine using skeletal muscle supernatant. This attractive approach and readily-available material could be a promising option for tissue repair/regeneration in the clinical setting. Cite this article: M. Yoshikawa, T. Nakasa, M. Ishikawa, N. Adachi, M. Ochi. Evaluation of autologous skeletal muscle-derived factors for regenerative medicine applications. Bone Joint Res 2017;6:277–283. DOI: 10.1302/2046-3758.65.BJR-2016-0187.R1


Bone & Joint Open
Vol. 4, Issue 10 | Pages 750 - 757
10 Oct 2023
Brenneis M Thewes N Holder J Stief F Braun S

Aims. Accurate skeletal age and final adult height prediction methods in paediatric orthopaedics are crucial for determining optimal timing of growth-guiding interventions and minimizing complications in treatments of various conditions. This study aimed to evaluate the accuracy of final adult height predictions using the central peak height (CPH) method with long leg X-rays and four different multiplier tables. Methods. This study included 31 patients who underwent temporary hemiepiphysiodesis for varus or valgus deformity of the leg between 2014 and 2020. The skeletal age at surgical intervention was evaluated using the CPH method with long leg radiographs. The true final adult height (FH. TRUE. ) was determined when the growth plates were closed. The final height prediction accuracy of four different multiplier tables (1. Bayley and Pinneau; 2. Paley et al; 3. Sanders – Greulich and Pyle (SGP); and 4. Sanders – peak height velocity (PHV)) was then compared using either skeletal age or chronological age. Results. All final adult height predictions overestimated the FH. TRUE. , with the SGP multiplier table having the lowest overestimation and lowest absolute deviation when using both chronological age and skeletal age. There were no significant differences in final height prediction accuracy between using skeletal age and chronological age with PHV (p = 0.652) or SGP multiplier tables (p = 0.969). Adult height predictions with chronological age and SGP (r = 0.769; p ≤ 0.001), as well as chronological age and PHV (r = 0.822; p ≤ 0.001), showed higher correlations with FH. TRUE. than predictions with skeletal age and SGP (r = 0.657; p ≤ 0.001) or skeletal age and PHV (r = 0.707; p ≤ 0.001). Conclusion. There was no significant improvement in adult height prediction accuracy when using the CPH method compared to chronological age alone. The study concludes that there is no advantage in routinely using the CPH method for skeletal age determination over the simple use of chronological age. The findings highlight the need for more accurate methods to predict final adult height in contemporary patient populations. Cite this article: Bone Jt Open 2023;4(10):750–757


Bone & Joint Open
Vol. 4, Issue 11 | Pages 873 - 880
17 Nov 2023
Swaby L Perry DC Walker K Hind D Mills A Jayasuriya R Totton N Desoysa L Chatters R Young B Sherratt F Latimer N Keetharuth A Kenison L Walters S Gardner A Ahuja S Campbell L Greenwood S Cole A

Aims. Scoliosis is a lateral curvature of the spine with associated rotation, often causing distress due to appearance. For some curves, there is good evidence to support the use of a spinal brace, worn for 20 to 24 hours a day to minimize the curve, making it as straight as possible during growth, preventing progression. Compliance can be poor due to appearance and comfort. A night-time brace, worn for eight to 12 hours, can achieve higher levels of curve correction while patients are supine, and could be preferable for patients, but evidence of efficacy is limited. This is the protocol for a randomized controlled trial of ‘full-time bracing’ versus ‘night-time bracing’ in adolescent idiopathic scoliosis (AIS). Methods. UK paediatric spine clinics will recruit 780 participants aged ten to 15 years-old with AIS, Risser stage 0, 1, or 2, and curve size (Cobb angle) 20° to 40° with apex at or below T7. Patients are randomly allocated 1:1, to either full-time or night-time bracing. A qualitative sub-study will explore communication and experiences of families in terms of bracing and research. Patient and Public Involvement & Engagement informed study design and will assist with aspects of trial delivery and dissemination. Discussion. The primary outcome is ‘treatment failure’ (Cobb angle progression to 50° or more before skeletal maturity); skeletal maturity is at Risser stage 4 in females and 5 in males, or ‘treatment success’ (Cobb angle less than 50° at skeletal maturity). The comparison is on a non-inferiority basis (non-inferiority margin 11%). Participants are followed up every six months while in brace, and at one and two years after skeletal maturity. Secondary outcomes include the Scoliosis Research Society 22 questionnaire and measures of quality of life, psychological effects of bracing, adherence, anxiety and depression, sleep, satisfaction, and educational attainment. All data will be collected through the British Spine Registry. Cite this article: Bone Jt Open 2023;4(11):873–880


Bone & Joint Open
Vol. 3, Issue 2 | Pages 123 - 129
1 Feb 2022
Bernard J Bishop T Herzog J Haleem S Lupu C Ajayi B Lui DF

Aims. Vertebral body tethering (VBT) is a non-fusion technique to correct scoliosis. It allows correction of scoliosis through growth modulation (GM) by tethering the convex side to allow concave unrestricted growth similar to the hemiepiphysiodesis concept. The other modality is anterior scoliosis correction (ASC) where the tether is able to perform most of the correction immediately where limited growth is expected. Methods. We conducted a retrospective analysis of clinical and radiological data of 20 patients aged between 9 and 17 years old, (with a 19 female: 1 male ratio) between January 2014 to December 2016 with a mean five-year follow-up (4 to 7). Results. There were ten patients in each group with a total of 23 curves operated on. VBT-GM mean age was 12.5 years (9 to 14) with a mean Risser classification of 0.63 (0 to 2) and VBT-ASC was 14.9 years (13 to 17) with a mean Risser classification of 3.66 (3 to 5). Mean preoperative VBT-GM Cobb was 47.4° (40° to 58°) with a Fulcrum unbend of 17.4 (1° to 41°), compared to VBT-ASC 56.5° (40° to 79°) with 30.6 (2° to 69°)unbend. Postoperative VBT-GM was 20.3° and VBT-ASC Cobb angle was 11.2°. The early postoperative correction rate was 54.3% versus 81% whereas Fulcrum Bending Correction Index (FBCI) was 93.1% vs 146.6%. The last Cobb angle on radiograph at mean five years’ follow-up was 19.4° (VBT-GM) and 16.5° (VBT-ASC). Patients with open triradiate cartilage (TRC) had three over-corrections. Overall, 5% of patients required fusion. This one patient alone had a over-correction, a second-stage tether release, and final conversion to fusion. Conclusion. We show a high success rate (95%) in helping children avoid fusion at five years post-surgery. VBT is a safe technique for correction of scoliosis in the skeletally immature patient. This is the first report at five years that shows two methods of VBT can be employed depending on the skeletal maturity of the patient: GM and ASC. Cite this article: Bone Jt Open 2022;3(2):123–129


The Bone & Joint Journal
Vol. 102-B, Issue 12 | Pages 1703 - 1708
1 Dec 2020
Miyanji F Pawelek J Nasto LA Simmonds A Parent S

Aims. Spinal fusion remains the gold standard in the treatment of idiopathic scoliosis. However, anterior vertebral body tethering (AVBT) is gaining widespread interest, despite the limited data on its efficacy. The aim of our study was to determine the clinical efficacy of AVBT in skeletally immature patients with idiopathic scoliosis. Methods. All consecutive skeletally immature patients with idiopathic scoliosis treated with AVBT enrolled in a longitudinal, multicentre, prospective database between 2013 and 2016 were analyzed. All patients were treated by one of two surgeons working at two independent centres. Data were collected prospectively in a multicentre database and supplemented retrospectively where necessary. Patients with a minimum follow-up of two years were included in the analysis. Clinical success was set a priori as a major coronal Cobb angle of < 35° at the most recent follow-up. Results. A total of 57 patients were included in the study. Their mean age was 12.7 years (SD 1.5; 8.2 to 16.7), with 95% being female. The mean preoperative Sanders score and Risser grade was 3.3 (SD 1.2), and 0.05 (0 to 3), respectively. The majority were thoracic tethers (96.5%) and the mean follow-up was 40.4 months (SD 9.3). The mean preoperative major curve of 51° (SD 10.9°; 31° to 81°) was significantly improved to a mean of 24.6° (SD 11.8°; 0° to 57°) at the first postoperative visit (45.6% (SD 17.6%; 7% to 107%); p < 0.001)) with further significant correction to a mean of 16.3° (SD 12.8°; -12 to 55; p < 0.001) at one year and a significant correction to a mean of 23° (SD 15.4°; -18° to 57°) at the final follow-up (42.9% (-16% to 147%); p < 0.001). Clinical success was achieved in 44 patients (77%). Most patients reached skeletal maturity, with a mean Risser score of 4.3 (SD 1.02), at final follow-up. The complication rate was 28.1% with a 15.8% rate of unplanned revision procedures. Conclusion. AVBT is associated with satisfactory correction of deformity and an acceptable complication rate when used in skeletally immature patients with idiopathic scoliosis. Improved patient selection and better implant technology may improve the 15.8% rate of revision surgery in these patients. Further scrutiny of the true effectiveness and long-term risks of this technique remains critical. Cite this article: Bone Joint J 2020;102-B(12):1703–1708


The Bone & Joint Journal
Vol. 103-B, Issue 8 | Pages 1428 - 1437
2 Aug 2021
Vogt B Roedl R Gosheger G Frommer A Laufer A Kleine-Koenig M Theil C Toporowski G

Aims. Temporary epiphysiodesis (ED) is commonly applied in children and adolescents to treat leg length discrepancies (LLDs) and tall stature. Traditional Blount staples or modern two-hole plates are used in clinical practice. However, they require accurate planning, precise surgical techniques, and attentive follow-up to achieve the desired outcome without complications. This study reports the results of ED using a novel rigid staple (RigidTack) incorporating safety, as well as technical and procedural success according to the idea, development, evaluation, assessment, long-term (IDEAL) study framework. Methods. A cohort of 56 patients, including 45 unilateral EDs for LLD and 11 bilateral EDs for tall stature, were prospectively analyzed. ED was performed with 222 rigid staples with a mean follow-up of 24.4 months (8 to 49). Patients with a predicted LLD of ≥ 2 cm at skeletal maturity were included. Mean age at surgery was 12.1 years (8 to 14). Correction and complication rates including implant-associated problems, and secondary deformities as well as perioperative parameters, were recorded (IDEAL stage 2a). These results were compared to historical cohorts treated for correction of LLD with two-hole plates or Blount staples. Results. The mean LLD was reduced from 25.2 mm (15 to 45) before surgery to 9.3 mm (6 to 25) at skeletal maturity. Implant-associated complications occurred in 4/56 treatments (7%), and secondary frontal plane deformities were detected in 5/45 legs (11%) of the LLD cohort. Including tall stature patients, the rate increased to 12/67 legs (18%). Sagittal plane deformities were observed during 1/45 LLD treatments (2%). Compared to two-hole plates and Blount staples, similar correction rates were observed in all devices. Lower rates of frontal and sagittal plane deformities were observed using rigid staples. Conclusion. Treatment of LLD using novel rigid staples appears a feasible and promising strategy. Secondary frontal and sagittal plane deformities remain a potential complication, although the rate seems to be lower in patients treated with rigid staples. Further comparative studies are needed to investigate this issue. Cite this article: Bone Joint J 2021;103-B(8):1428–1437


Bone & Joint Research
Vol. 12, Issue 7 | Pages 397 - 411
3 Jul 2023
Ruan X Gu J Chen M Zhao F Aili M Zhang D

Osteoarthritis (OA) is a chronic degenerative joint disease characterized by progressive cartilage degradation, synovial membrane inflammation, osteophyte formation, and subchondral bone sclerosis. Pathological changes in cartilage and subchondral bone are the main processes in OA. In recent decades, many studies have demonstrated that activin-like kinase 3 (ALK3), a bone morphogenetic protein receptor, is essential for cartilage formation, osteogenesis, and postnatal skeletal development. Although the role of bone morphogenetic protein (BMP) signalling in articular cartilage and bone has been extensively studied, many new discoveries have been made in recent years around ALK3 targets in articular cartilage, subchondral bone, and the interaction between the two, broadening the original knowledge of the relationship between ALK3 and OA. In this review, we focus on the roles of ALK3 in OA, including cartilage and subchondral bone and related cells. It may be helpful to seek more efficient drugs or treatments for OA based on ALK3 signalling in future


Bone & Joint Open
Vol. 1, Issue 4 | Pages 55 - 63
7 Apr 2020
Terjesen T Horn J

Aims. When the present study was initiated, we changed the treatment for late-detected developmental dislocation of the hip (DDH) from several weeks of skin traction to markedly shorter traction time. The aim of this prospective study was to evaluate this change, with special emphasis on the rate of stable closed reduction according to patient age, the development of the acetabulum, and the outcome at skeletal maturity. Methods. From 1996 to 2005, 49 children (52 hips) were treated for late-detected DDH. Their mean age was 13.3 months (3 to 33) at reduction. Prereduction skin traction was used for a mean of 11 days (0 to 27). Gentle closed reduction under general anaesthesia was attempted in all the hips. Concurrent pelvic osteotomy was not performed. The hips were evaluated at one, three and five years after reduction, at age eight to ten years, and at skeletal maturity. Mean age at the last follow-up was 15.7 years (13 to 21). Results. Stable closed reduction was obtained in 36 hips (69%). Open reduction was more often necessary in patients ≥ 18 months of age at reduction (50%) compared with those under 18 months (24%). Residual hip dysplasia/subluxation occurred in 12 hips and was significantly associated with avascular necrosis (AVN) and with high acetabular index and low femoral head coverage the first years after reduction. Further surgery, mostly pelvic and femoral osteotomies to correct subluxation, was performed in eight hips (15%). The radiological outcome at skeletal maturity was satisfactory (Severin grades 1 or 2) in 43 hips (83%). Conclusions. Gentle closed reduction can be attempted in children up to three years of age, but is likely to be less successful in children aged over 18 months. There is a marked trend to spontaneous improvement of the acetabulum after reduction, even in patients aged over 18 months and therefore simultaneous pelvic osteotomy is not always necessary


Bone & Joint Research
Vol. 9, Issue 3 | Pages 130 - 138
1 Mar 2020
Qi X Yu F Wen Y Li P Cheng B Ma M Cheng S Zhang L Liang C Liu L Zhang F

Aims. Osteoarthritis (OA) is the most prevalent joint disease. However, the specific and definitive genetic mechanisms of OA are still unclear. Methods. Tissue-related transcriptome-wide association studies (TWAS) of hip OA and knee OA were performed utilizing the genome-wide association study (GWAS) data of hip OA and knee OA (including 2,396 hospital-diagnosed hip OA patients versus 9,593 controls, and 4,462 hospital-diagnosed knee OA patients versus 17,885 controls) and gene expression reference to skeletal muscle and blood. The OA-associated genes identified by TWAS were further compared with the differentially expressed genes detected by the messenger RNA (mRNA) expression profiles of hip OA and knee OA. Functional enrichment and annotation analysis of identified genes was performed by the DAVID and FUMAGWAS tools. Results. We detected 33 common genes, eight common gene ontology (GO) terms, and one common pathway for hip OA, such as calcium and integrin-binding protein 1 (CIB1) (PTWAS = 0.025, FCmRNA = -1.575 for skeletal muscle), adrenomedullin (ADM) (PTWAS = 0.022, FCmRNA = -4.644 for blood), Golgi apparatus (PTWAS <0.001, PmRNA = 0.012 for blood), and phosphatidylinositol 3' -kinase-protein kinase B (PI3K-Akt) signalling pathway (PTWAS = 0.033, PmRNA = 0.005 for blood). For knee OA, we detected 24 common genes, eight common GO terms, and two common pathways, such as histocompatibility complex, class II, DR beta 1 (HLA-DRB1) (PTWAS = 0.040, FCmRNA = 4.062 for skeletal muscle), Follistatin-like 1 (FSTL1) (PTWAS = 0.048, FCmRNA = 3.000 for blood), cytoplasm (PTWAS < 0.001, PmRNA = 0.005 for blood), and complement and coagulation cascades (PTWAS = 0.017, PmRNA = 0.001 for skeletal muscle). Conclusion. We identified a group of OA-associated genes and pathways, providing novel clues for understanding the genetic mechanism of OA. Cite this article:Bone Joint Res. 2020;9(3):130–138


Bone & Joint Open
Vol. 3, Issue 10 | Pages 841 - 849
27 Oct 2022
Knight R Keene DJ Dutton SJ Handley R Willett K

Aims. The rationale for exacting restoration of skeletal anatomy after unstable ankle fracture is to improve outcomes by reducing complications from malunion; however, current definitions of malunion lack confirmatory clinical evidence. Methods. Radiological (absolute radiological measurements aided by computer software) and clinical (clinical interpretation of radiographs) definitions of malunion were compared within the Ankle Injury Management (AIM) trial cohort, including people aged ≥ 60 years with an unstable ankle fracture. Linear regressions were used to explore the relationship between radiological malunion (RM) at six months and changes in function at three years. Function was assessed with the Olerud-Molander Ankle Score (OMAS), with a minimal clinically important difference set as six points, as per the AIM trial. Piecewise linear models were used to investigate new radiological thresholds which better explain symptom impact on ankle function. Results. Previously described measures of RM and surgeon opinion of clinically significant malunion (CSM) were shown to be related but with important differences. CSM was more strongly related to outcome (-13.9 points on the OMAS; 95% confidence interval (CI) -21.9 to -5.4) than RM (-5.5 points; 95% CI -9.8 to -1.2). Existing malunion thresholds for talar tilt and tibiofibular clear space were shown to be slightly conservative; new thresholds which better explain function were identified (talar tilt > 2.4°; tibiofibular clear space > 6 mm). Based on this new definition the presence of RM had an impact on function, which was statistically significant, but the clinical significance was uncertain (-9.1 points; 95% CI -13.8 to -4.4). In subsequent analysis, RM of a posterior malleolar fracture was shown to have a statistically significant impact on OMAS change scores, but the clinical significance was uncertain (-11.6 points; 95% CI -21.9 to -0.6). Conclusion. These results provide clinical evidence which supports the previously accepted definitions. Further research to investigate more conservative clinical thresholds for malunion is indicated. Cite this article: Bone Jt Open 2022;3(10):841–849


Bone & Joint Research
Vol. 5, Issue 12 | Pages 610 - 618
1 Dec 2016
Abubakar AA Noordin MM Azmi TI Kaka U Loqman MY

In vivo animal experimentation has been one of the cornerstones of biological and biomedical research, particularly in the field of clinical medicine and pharmaceuticals. The conventional in vivo model system is invariably associated with high production costs and strict ethical considerations. These limitations led to the evolution of an ex vivo model system which partially or completely surmounted some of the constraints faced in an in vivo model system. The ex vivo rodent bone culture system has been used to elucidate the understanding of skeletal physiology and pathophysiology for more than 90 years. This review attempts to provide a brief summary of the historical evolution of the rodent bone culture system with emphasis on the strengths and limitations of the model. It encompasses the frequency of use of rats and mice for ex vivo bone studies, nutritional requirements in ex vivo bone growth and emerging developments and technologies. This compilation of information could assist researchers in the field of regenerative medicine and bone tissue engineering towards a better understanding of skeletal growth and development for application in general clinical medicine. Cite this article: A. A. Abubakar, M. M. Noordin, T. I. Azmi, U. Kaka, M. Y. Loqman. The use of rats and mice as animal models in ex vivo bone growth and development studies. Bone Joint Res 2016;5:610–618. DOI: 10.1302/2046-3758.512.BJR-2016-0102.R2


Bone & Joint Research
Vol. 9, Issue 6 | Pages 302 - 310
1 Jun 2020
Tibbo ME Limberg AK Salib CG Turner TW McLaury AR Jay AG Bettencourt JW Carter JM Bolon B Berry DJ Morrey ME Sanchez-Sotelo J van Wijnen AJ Abdel MP

Aims. Arthrofibrosis is a relatively common complication after joint injuries and surgery, particularly in the knee. The present study used a previously described and validated rabbit model to assess the biomechanical, histopathological, and molecular effects of the mast cell stabilizer ketotifen on surgically induced knee joint contractures in female rabbits. Methods. A group of 12 skeletally mature rabbits were randomly divided into two groups. One group received subcutaneous (SQ) saline, and a second group received SQ ketotifen injections. Biomechanical data were collected at eight, ten, 16, and 24 weeks. At the time of necropsy, posterior capsule tissue was collected for histopathological and gene expression analyses (messenger RNA (mRNA) and protein). Results. At the 24-week timepoint, there was a statistically significant increase in passive extension among rabbits treated with ketotifen compared to those treated with saline (p = 0.03). However, no difference in capsular stiffness was detected. Histopathological data failed to demonstrate a decrease in the density of fibrous tissue or a decrease in α-smooth muscle actin (α-SMA) staining with ketotifen treatment. In contrast, tryptase and α-SMA protein expression in the ketotifen group were decreased when compared to saline controls (p = 0.007 and p = 0.01, respectively). Furthermore, there was a significant decrease in α-SMA (ACTA2) gene expression in the ketotifen group compared to the control group (p < 0.001). Conclusion. Collectively, these data suggest that ketotifen mitigates the severity of contracture formation in a rabbit model of arthrofibrosis. Cite this article: Bone Joint Res 2020;9(6):302–310


Bone & Joint Research
Vol. 9, Issue 3 | Pages 99 - 107
1 Mar 2020
Chang C Jou I Wu T Su F Tai T

Aims. Cigarette smoking has a negative impact on the skeletal system, causes a decrease in bone mass in both young and old patients, and is considered a risk factor for the development of osteoporosis. In addition, it disturbs the bone healing process and prolongs the healing time after fractures. The mechanisms by which cigarette smoking impairs fracture healing are not fully understood. There are few studies reporting the effects of cigarette smoking on new blood vessel formation during the early stage of fracture healing. We tested the hypothesis that cigarette smoke inhalation may suppress angiogenesis and delay fracture healing. Methods. We established a custom-made chamber with airflow for rats to inhale cigarette smoke continuously, and tested our hypothesis using a femoral osteotomy model, radiograph and microCT imaging, and various biomechanical and biological tests. Results. In the smoking group, Western blot analysis and immunohistochemical staining revealed less expression of vascular endothelial growth factor (VEGF) and von Willebrand factor (vWF). The smoking group also had a lower microvessel density than the control group. Image and biochemical analysis also demonstrated delayed bone healing. Conclusion. Cigarette smoke inhalation was associated with decreased expression of angiogenic markers in the early bone healing phase and with impaired bone healing. Cite this article:Bone Joint Res. 2020;9(3):99–107


Bone & Joint Research
Vol. 4, Issue 7 | Pages 105 - 116
1 Jul 2015
Shea CA Rolfe RA Murphy P

Construction of a functional skeleton is accomplished through co-ordination of the developmental processes of chondrogenesis, osteogenesis, and synovial joint formation. Infants whose movement in utero is reduced or restricted and who subsequently suffer from joint dysplasia (including joint contractures) and thin hypo-mineralised bones, demonstrate that embryonic movement is crucial for appropriate skeletogenesis. This has been confirmed in mouse, chick, and zebrafish animal models, where reduced or eliminated movement consistently yields similar malformations and which provide the possibility of experimentation to uncover the precise disturbances and the mechanisms by which movement impacts molecular regulation. Molecular genetic studies have shown the important roles played by cell communication signalling pathways, namely Wnt, Hedgehog, and transforming growth factor-beta/bone morphogenetic protein. These pathways regulate cell behaviours such as proliferation and differentiation to control maturation of the skeletal elements, and are affected when movement is altered. Cell contacts to the extra-cellular matrix as well as the cytoskeleton offer a means of mechanotransduction which could integrate mechanical cues with genetic regulation. Indeed, expression of cytoskeletal genes has been shown to be affected by immobilisation. In addition to furthering our understanding of a fundamental aspect of cell control and differentiation during development, research in this area is applicable to the engineering of stable skeletal tissues from stem cells, which relies on an understanding of developmental mechanisms including genetic and physical criteria. A deeper understanding of how movement affects skeletogenesis therefore has broader implications for regenerative therapeutics for injury or disease, as well as for optimisation of physical therapy regimes for individuals affected by skeletal abnormalities. Cite this article: Bone Joint Res 2015;4:105–116


Bone & Joint Open
Vol. 4, Issue 6 | Pages 424 - 431
5 Jun 2023
Christ AB Piple AS Gettleman BS Duong A Chen M Wang JC Heckmann ND Menendez L

Aims

The modern prevalence of primary tumours causing metastatic bone disease is ill-defined in the oncological literature. Therefore, the purpose of this study is to identify the prevalence of primary tumours in the setting of metastatic bone disease, as well as reported rates of pathological fracture, postoperative complications, 90-day mortality, and 360-day mortality for each primary tumour subtype.

Methods

The Premier Healthcare Database was queried to identify all patients who were diagnosed with metastatic bone disease from January 2015 to December 2020. The prevalence of all primary tumour subtypes was tabulated. Rates of long bone pathological fracture, 90-day mortality, and 360-day mortality following surgical treatment of pathological fracture were assessed for each primary tumour subtype. Patient characteristics and postoperative outcomes were analyzed based upon whether patients had impending fractures treated prophylactically versus treated completed fractures.


Bone & Joint Research
Vol. 12, Issue 10 | Pages 644 - 653
10 Oct 2023
Hinz N Butscheidt S Jandl NM Rohde H Keller J Beil FT Hubert J Rolvien T

Aims

The management of periprosthetic joint infection (PJI) remains a major challenge in orthopaedic surgery. In this study, we aimed to characterize the local bone microstructure and metabolism in a clinical cohort of patients with chronic PJI.

Methods

Periprosthetic femoral trabecular bone specimens were obtained from patients suffering from chronic PJI of the hip and knee (n = 20). Microbiological analysis was performed on preoperative joint aspirates and tissue specimens obtained during revision surgery. Microstructural and cellular bone parameters were analyzed in bone specimens by histomorphometry on undecalcified sections complemented by tartrate-resistant acid phosphatase immunohistochemistry. Data were compared with control specimens obtained during primary arthroplasty (n = 20) and aseptic revision (n = 20).


Bone & Joint Open
Vol. 4, Issue 8 | Pages 643 - 651
24 Aug 2023
Langit MB Tay KS Al-Omar HK Barlow G Bates J Chuo CB Muir R Sharma H

Aims

The standard of wide tumour-like resection for chronic osteomyelitis (COM) has been challenged recently by adequate debridement. This paper reviews the evolution of surgical debridement for long bone COM, and presents the outcome of adequate debridement in a tertiary bone infection unit.

Methods

We analyzed the retrospective record review from 2014 to 2020 of patients with long bone COM. All were managed by multidisciplinary infection team (MDT) protocol. Adequate debridement was employed for all cases, and no case of wide resection was included.


Bone & Joint Research
Vol. 12, Issue 4 | Pages 294 - 305
20 Apr 2023
Aquilina AL Claireaux H Aquilina CO Tutton E Fitzpatrick R Costa ML Griffin XL

Aims

Open lower limb fracture is life-changing, resulting in substantial morbidity and resource demand, while inconsistent outcome-reporting hampers systematic review and meta-analysis. A core outcome set establishes consensus among key stakeholders for the recommendation of a minimum set of outcomes. This study aims to define a core outcome set for adult open lower limb fracture.

Methods

Candidate outcomes were identified from a previously published systematic review and a secondary thematic analysis of 25 patient interviews exploring the lived experience of recovery from open lower limb fracture. Outcomes were categorized and sequentially refined using healthcare professional and patient structured discussion groups. Consensus methods included a multi-stakeholder two-round online Delphi survey and a consensus meeting attended by a purposive sample of stakeholders, facilitated discussion, and voting using a nominal group technique.


Bone & Joint Research
Vol. 7, Issue 2 | Pages 148 - 156
1 Feb 2018
Pinheiro M Dobson CA Perry D Fagan MJ

Objectives. Legg–Calvé–Perthes’ disease (LCP) is an idiopathic osteonecrosis of the femoral head that is most common in children between four and eight years old. The factors that lead to the onset of LCP are still unclear; however, it is believed that interruption of the blood supply to the developing epiphysis is an important factor in the development of the condition. Methods. Finite element analysis modelling of the blood supply to the juvenile epiphysis was investigated to understand under which circumstances the blood vessels supplying the femoral epiphysis could become obstructed. The identification of these conditions is likely to be important in understanding the biomechanics of LCP. Results. The results support the hypothesis that vascular obstruction to the epiphysis may arise when there is delayed ossification and when articular cartilage has reduced stiffness under compression. Conclusion. The findings support the theory of vascular occlusion as being important in the pathophysiology of Perthes disease. Cite this article: M. Pinheiro, C. A. Dobson, D. Perry, M. J. Fagan. New insights into the biomechanics of Legg-Calvé-Perthes’ disease: The Role of Epiphyseal Skeletal Immaturity in Vascular Obstruction. Bone Joint Res 2018;7:148–156. DOI: 10.1302/2046-3758.72.BJR-2017-0191.R1


The Bone & Joint Journal
Vol. 105-B, Issue 5 | Pages 471 - 473
1 May 2023
Peterson N Perry DC

Salter-Harris II fractures of the distal tibia affect children frequently, and when they are displaced present a treatment dilemma. Treatment primarily aims to restore alignment and prevent premature physeal closure, as this can lead to angular deformity, limb length difference, or both. Current literature is of poor methodological quality and is contradictory as to whether conservative or surgical management is superior in avoiding complications and adverse outcomes. A state of clinical equipoise exists regarding whether displaced distal tibial Salter-Harris II fractures in children should be treated with surgery to achieve anatomical reduction, or whether cast treatment alone will lead to a satisfactory outcome. Systematic review and meta-analysis has concluded that high-quality prospective multicentre research is needed to answer this question. The Outcomes of Displaced Distal tibial fractures: Surgery Or Casts in KidS (ODD SOCKS) trial, funded by the National Institute for Health and Care Research, aims to provide this high-quality research in order to answer this question, which has been identified as a top-five research priority by the British Society for Children’s Orthopaedic Surgery.

Cite this article: Bone Joint J 2023;105-B(5):471–473.


Bone & Joint Research
Vol. 11, Issue 7 | Pages 439 - 452
13 Jul 2022
Sun Q Li G Liu D Xie W Xiao W Li Y Cai M

Osteoarthritis (OA) is a highly prevalent degenerative joint disorder characterized by joint pain and physical disability. Aberrant subchondral bone induces pathological changes and is a major source of pain in OA. In the subchondral bone, which is highly innervated, nerves have dual roles in pain sensation and bone homeostasis regulation. The interaction between peripheral nerves and target cells in the subchondral bone, and the interplay between the sensory and sympathetic nervous systems, allow peripheral nerves to regulate subchondral bone homeostasis. Alterations in peripheral innervation and local transmitters are closely related to changes in nociception and subchondral bone homeostasis, and affect the progression of OA. Recent literature has substantially expanded our understanding of the physiological and pathological distribution and function of specific subtypes of neurones in bone. This review summarizes the types and distribution of nerves detected in the tibial subchondral bone, their cellular and molecular interactions with bone cells that regulate subchondral bone homeostasis, and their role in OA pain. A comprehensive understanding and further investigation of the functions of peripheral innervation in the subchondral bone will help to develop novel therapeutic approaches to effectively prevent OA, and alleviate OA pain.

Cite this article: Bone Joint Res 2022;11(7):439–452.


Bone & Joint Research
Vol. 7, Issue 6 | Pages 397 - 405
1 Jun 2018
Morcos MW Al-Jallad H Li J Farquharson C Millán JL Hamdy RC Murshed M

Objectives. Bone fracture healing is regulated by a series of complex physicochemical and biochemical processes. One of these processes is bone mineralization, which is vital for normal bone development. Phosphatase, orphan 1 (PHOSPHO1), a skeletal tissue-specific phosphatase, has been shown to be involved in the mineralization of the extracellular matrix and to maintain the structural integrity of bone. In this study, we examined how PHOSPHO1 deficiency might affect the healing and quality of fracture callus in mice. Methods. Tibial fractures were created and then stabilized in control wild-type (WT) and Phospho1. -/-. mice (n = 16 for each group; mixed gender, each group carrying equal number of male and female mice) at eight weeks of age. Fractures were allowed to heal for four weeks and then the mice were euthanized and their tibias analyzed using radiographs, micro-CT (μCT), histology, histomorphometry and three-point bending tests. Results. The μCT and radiographic analyses revealed a mild reduction of bone volume in Phospho1. -/-. callus, although it was not statistically significant. An increase in trabecular number and a decrease in trabecular thickness and separation were observed in Phospho1. -/-. callus in comparison with the WT callus. Histomorphometric analyses showed that there was a marked increase of osteoid volume over bone volume in the Phospho1. -/-. callus. The three-point bending test showed that Phospho1. -/-. fractured bone had more of an elastic characteristic than the WT bone. Conclusion. Our work suggests that PHOSPHO1 plays an integral role during bone fracture repair and may be a therapeutic target to improve the fracture healing process. Cite this article: M. W. Morcos, H. Al-Jallad, J. Li, C. Farquharson, J. L. Millán, R. C. Hamdy, M. Murshed. PHOSPHO1 is essential for normal bone fracture healing: An Animal Study. Bone Joint Res 2018;7:397–405. DOI: 10.1302/2046-3758.76.BJR-2017-0140.R2


Bone & Joint Research
Vol. 7, Issue 2 | Pages 173 - 178
1 Feb 2018
Peng X Wu X Zhang J Zhang G Li G Pan X

Osteoporosis is a systemic skeletal disorder characterized by reduced bone mass and deterioration of bone microarchitecture, which results in increased bone fragility and fracture risk. Casein kinase 2-interacting protein-1 (CKIP-1) is a protein that plays an important role in regulation of bone formation. The effect of CKIP-1 on bone formation is mainly mediated through negative regulation of the bone morphogenetic protein pathway. In addition, CKIP-1 has an important role in the progression of osteoporosis. This review provides a summary of the recent studies on the role of CKIP-1 in osteoporosis development and treatment. Cite this article: X. Peng, X. Wu, J. Zhang, G. Zhang, G. Li, X. Pan. The role of CKIP-1 in osteoporosis development and treatment. Bone Joint Res 2018;7:173–178. DOI: 10.1302/2046-3758.72.BJR-2017-0172.R1


Bone & Joint Open
Vol. 5, Issue 3 | Pages 236 - 242
22 Mar 2024
Guryel E McEwan J Qureshi AA Robertson A Ahluwalia R

Aims

Ankle fractures are common injuries and the third most common fragility fracture. In all, 40% of ankle fractures in the frail are open and represent a complex clinical scenario, with morbidity and mortality rates similar to hip fracture patients. They have a higher risk of complications, such as wound infections, malunion, hospital-acquired infections, pressure sores, veno-thromboembolic events, and significant sarcopaenia from prolonged bed rest.

Methods

A modified Delphi method was used and a group of experts with a vested interest in best practice were invited from the British Foot and Ankle Society (BOFAS), British Orthopaedic Association (BOA), Orthopaedic Trauma Society (OTS), British Association of Plastic & Reconstructive Surgeons (BAPRAS), British Geriatric Society (BGS), and the British Limb Reconstruction Society (BLRS).


Bone & Joint Open
Vol. 5, Issue 3 | Pages 218 - 226
15 Mar 2024
Voigt JD Potter BK Souza J Forsberg J Melton D Hsu JR Wilke B

Aims

Prior cost-effectiveness analyses on osseointegrated prosthesis for transfemoral unilateral amputees have analyzed outcomes in non-USA countries using generic quality of life instruments, which may not be appropriate when evaluating disease-specific quality of life. These prior analyses have also focused only on patients who had failed a socket-based prosthesis. The aim of the current study is to use a disease-specific quality of life instrument, which can more accurately reflect a patient’s quality of life with this condition in order to evaluate cost-effectiveness, examining both treatment-naïve and socket refractory patients.

Methods

Lifetime Markov models were developed evaluating active healthy middle-aged male amputees. Costs of the prostheses, associated complications, use/non-use, and annual costs of arthroplasty parts and service for both a socket and osseointegrated (OPRA) prosthesis were included. Effectiveness was evaluated using the questionnaire for persons with a transfemoral amputation (Q-TFA) until death. All costs and Q-TFA were discounted at 3% annually. Sensitivity analyses on those cost variables which affected a change in treatment (OPRA to socket, or socket to OPRA) were evaluated to determine threshold values. Incremental cost-effectiveness ratios (ICERs) were calculated.


The Bone & Joint Journal
Vol. 106-B, Issue 7 | Pages 744 - 750
1 Jul 2024
Saeed A Bradley CS Verma Y Kelley SP

Aims

Radiological residual acetabular dysplasia (RAD) has been reported in up to 30% of children who had successful brace treatment of infant developmental dysplasia of the hip (DDH). Predicting those who will resolve and those who may need corrective surgery is important to optimize follow-up protocols. In this study we have aimed to identify the prevalence and predictors of RAD at two years and five years post-bracing.

Methods

This was a single-centre, prospective longitudinal cohort study of infants with DDH managed using a published, standardized Pavlik harness protocol between January 2012 and December 2016. RAD was measured at two years’ mean follow-up using acetabular index-lateral edge (AI-L) and acetabular index-sourcil (AI-S), and at five years using AI-L, AI-S, centre-edge angle (CEA), and acetabular depth ratio (ADR). Each hip was classified based on published normative values for normal, borderline (1 to 2 standard deviations (SDs)), or dysplastic (> 2 SDs) based on sex, age, and laterality.


Bone & Joint Open
Vol. 5, Issue 3 | Pages 243 - 251
25 Mar 2024
Wan HS Wong DLL To CS Meng N Zhang T Cheung JPY

Aims

This systematic review aims to identify 3D predictors derived from biplanar reconstruction, and to describe current methods for improving curve prediction in patients with mild adolescent idiopathic scoliosis.

Methods

A comprehensive search was conducted by three independent investigators on MEDLINE, PubMed, Web of Science, and Cochrane Library. Search terms included “adolescent idiopathic scoliosis”,“3D”, and “progression”. The inclusion and exclusion criteria were carefully defined to include clinical studies. Risk of bias was assessed with the Quality in Prognostic Studies tool (QUIPS) and Appraisal tool for Cross-Sectional Studies (AXIS), and level of evidence for each predictor was rated with the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) approach. In all, 915 publications were identified, with 377 articles subjected to full-text screening; overall, 31 articles were included.


Bone & Joint Research
Vol. 12, Issue 2 | Pages 147 - 154
20 Feb 2023
Jia Y Qi X Ma M Cheng S Cheng B Liang C Guo X Zhang F

Aims

Osteoporosis (OP) is a metabolic bone disease, characterized by a decrease in bone mineral density (BMD). However, the research of regulatory variants has been limited for BMD. In this study, we aimed to explore novel regulatory genetic variants associated with BMD.

Methods

We conducted an integrative analysis of BMD genome-wide association study (GWAS) and regulatory single nucleotide polymorphism (rSNP) annotation information. Firstly, the discovery GWAS dataset and replication GWAS dataset were integrated with rSNP annotation database to obtain BMD associated SNP regulatory elements and SNP regulatory element-target gene (E-G) pairs, respectively. Then, the common genes were further subjected to HumanNet v2 to explore the biological effects.


Bone & Joint Open
Vol. 5, Issue 4 | Pages 367 - 373
26 Apr 2024
Reinhard J Lang S Walter N Schindler M Bärtl S Szymski D Alt V Rupp M

Aims

Periprosthetic joint infection (PJI) demonstrates the most feared complication after total joint replacement (TJR). The current work analyzes the demographic, comorbidity, and complication profiles of all patients who had in-hospital treatment due to PJI. Furthermore, it aims to evaluate the in-hospital mortality of patients with PJI and analyze possible risk factors in terms of secondary diagnosis, diagnostic procedures, and complications.

Methods

In a retrospective, cross-sectional study design, we gathered all patients with PJI (International Classification of Diseases (ICD)-10 code: T84.5) and resulting in-hospital treatment in Germany between 1 January 2019 and 31 December 2022. Data were provided by the Institute for the Hospital Remuneration System in Germany. Demographic data, in-hospital deaths, need for intensive care therapy, secondary diagnosis, complications, and use of diagnostic instruments were assessed. Odds ratios (ORs) with 95% confidence intervals (CIs) for in-hospital mortality were calculated.


Bone & Joint Research
Vol. 12, Issue 1 | Pages 80 - 90
20 Jan 2023
Xu J Si H Zeng Y Wu Y Zhang S Liu Y Li M Shen B

Aims

Degenerative cervical spondylosis (DCS) is a common musculoskeletal disease that encompasses a wide range of progressive degenerative changes and affects all components of the cervical spine. DCS imposes very large social and economic burdens. However, its genetic basis remains elusive.

Methods

Predicted whole-blood and skeletal muscle gene expression and genome-wide association study (GWAS) data from a DCS database were integrated, and functional summary-based imputation (FUSION) software was used on the integrated data. A transcriptome-wide association study (TWAS) was conducted using FUSION software to assess the association between predicted gene expression and DCS risk. The TWAS-identified genes were verified via comparison with differentially expressed genes (DEGs) in DCS RNA expression profiles in the Gene Expression Omnibus (GEO) (Accession Number: GSE153761). The Functional Mapping and Annotation (FUMA) tool for genome-wide association studies and Meta tools were used for gene functional enrichment and annotation analysis.


Bone & Joint Open
Vol. 5, Issue 1 | Pages 69 - 77
25 Jan 2024
Achten J Appelbe D Spoors L Peckham N Kandiyali R Mason J Ferguson D Wright J Wilson N Preston J Moscrop A Costa M Perry DC

Aims

The management of fractures of the medial epicondyle is one of the greatest controversies in paediatric fracture care, with uncertainty concerning the need for surgery. The British Society of Children’s Orthopaedic Surgery prioritized this as their most important research question in paediatric trauma. This is the protocol for a randomized controlled, multicentre, prospective superiority trial of operative fixation versus nonoperative treatment for displaced medial epicondyle fractures: the Surgery or Cast of the EpicoNdyle in Children’s Elbows (SCIENCE) trial.

Methods

Children aged seven to 15 years old inclusive, who have sustained a displaced fracture of the medial epicondyle, are eligible to take part. Baseline function using the Patient-Reported Outcomes Measurement Information System (PROMIS) upper limb score, pain measured using the Wong Baker FACES pain scale, and quality of life (QoL) assessed with the EuroQol five-dimension questionnaire for younger patients (EQ-5D-Y) will be collected. Each patient will be randomly allocated (1:1, stratified using a minimization algorithm by centre and initial elbow dislocation status (i.e. dislocated or not-dislocated at presentation to the emergency department)) to either a regimen of the operative fixation or non-surgical treatment.


Bone & Joint Open
Vol. 3, Issue 7 | Pages 557 - 565
11 Jul 2022
Meier MK Reche J Schmaranzer F von Tengg-Kobligk H Steppacher SD Tannast M Novais EN Lerch TD

Aims

The frequency of severe femoral retroversion is unclear in patients with femoroacetabular impingement (FAI). This study aimed to investigate mean femoral version (FV), the frequency of absolute femoral retroversion, and the combination of decreased FV and acetabular retroversion (AR) in symptomatic patients with FAI subtypes.

Methods

A retrospective institutional review board-approved observational study was performed with 333 symptomatic patients (384 hips) with hip pain due to FAI evaluated for hip preservation surgery. Overall, 142 patients (165 hips) had cam-type FAI, while 118 patients (137 hips) had mixed-type FAI. The allocation to each subgroup was based on reference values calculated on anteroposterior radiographs. CT/MRI-based measurement of FV (Murphy method) and AV were retrospectively compared among five FAI subgroups. Frequency of decreased FV < 10°, severely decreased FV < 5°, and absolute femoral retroversion (FV < 0°) was analyzed.


Bone & Joint Research
Vol. 12, Issue 1 | Pages 58 - 71
17 Jan 2023
Dagneaux L Limberg AK Owen AR Bettencourt JW Dudakovic A Bayram B Gades NM Sanchez-Sotelo J Berry DJ van Wijnen A Morrey ME Abdel MP

Aims

As has been shown in larger animal models, knee immobilization can lead to arthrofibrotic phenotypes. Our study included 168 C57BL/6J female mice, with 24 serving as controls, and 144 undergoing a knee procedure to induce a contracture without osteoarthritis (OA).

Methods

Experimental knees were immobilized for either four weeks (72 mice) or eight weeks (72 mice), followed by a remobilization period of zero weeks (24 mice), two weeks (24 mice), or four weeks (24 mice) after suture removal. Half of the experimental knees also received an intra-articular injury. Biomechanical data were collected to measure passive extension angle (PEA). Histological data measuring area and thickness of posterior and anterior knee capsules were collected from knee sections.


Bone & Joint Research
Vol. 12, Issue 12 | Pages 722 - 733
6 Dec 2023
Fu T Chen W Wang Y Chang C Lin T Wong C

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.


Bone & Joint Research
Vol. 12, Issue 5 | Pages 311 - 312
5 May 2023
Xu C Liu Y

Cite this article: Bone Joint Res 2023;12(5):311–312.


Bone & Joint Open
Vol. 3, Issue 11 | Pages 894 - 897
15 Nov 2022
Makaram NS Murray IR Geeslin AG Chahla J LaPrade RF

Aims

Multiligament knee injuries (MLKI) are devastating injuries that can result in significant morbidity and time away from sport. There remains considerable variation in strategies employed for investigation, indications for operative intervention, outcome reporting, and rehabilitation following these injuries. At present no study has yet provided a comprehensive overview evaluating the extent, range, and overall summary of the published literature pertaining to MLKI. Our aim is to perform a methodologically rigorous scoping review, mapping the literature evaluating the diagnosis and management of MLKI.

Methods

This scoping review will address three aims: firstly, to map the current extent and nature of evidence for diagnosis and management of MLKI; secondly, to summarize and disseminate existing research findings to practitioners; and thirdly, to highlight gaps in current literature. A three-step search strategy as described by accepted methodology will be employed to identify peer-reviewed literature including reviews, technical notes, opinion pieces, and original research. An initial limited search will be performed to determine suitable search terms, followed by an expanded search of four electronic databases (MEDLINE, EMBASE, Cochrane Database of Systematic Reviews, and Web of Science). Two reviewers will independently screen identified studies for final inclusion.


The Bone & Joint Journal
Vol. 105-B, Issue 6 | Pages 711 - 716
1 Jun 2023
Ali MS Khattak M Metcalfe D Perry DC

Aims

This study aimed to evaluate the relationship between hip shape and mid-term function in Perthes’ disease. It also explored whether the modified three-group Stulberg classification can offer similar prognostic information to the five-group system.

Methods

A total of 136 individuals aged 12 years or older who had Perthes’ disease in childhood completed the Patient-Reported Outcomes Measurement Information System (PROMIS) Mobility score (function), Nonarthritic Hip Score (NAHS) (function), EuroQol five-dimension five-level questionnaire (EQ-5D-5L) score (quality of life), and the numeric rating scale for pain (NRS). The Stulberg class of the participants’ hip radiographs were evaluated by three fellowship-trained paediatric orthopaedic surgeons. Hip shape and Stulberg class were compared to PROM scores.


Bone & Joint Open
Vol. 4, Issue 9 | Pages 689 - 695
7 Sep 2023
Lim KBL Lee NKL Yeo BS Lim VMM Ng SWL Mishra N

Aims

To determine whether side-bending films in scoliosis are assessed for adequacy in clinical practice; and to introduce a novel method for doing so.

Methods

Six surgeons and eight radiographers were invited to participate in four online surveys. The generic survey comprised erect and left and right bending radiographs of eight individuals with scoliosis, with an average age of 14.6 years. Respondents were asked to indicate whether each bending film was optimal (adequate) or suboptimal. In the first survey, they were also asked if they currently assessed the adequacy of bending films. A similar second survey was sent out two weeks later, using the same eight cases but in a different order. In the third survey, a guide for assessing bending film adequacy was attached along with the radiographs to introduce the novel T1-45B method, in which the upper endplate of T1 must tilt ≥ 45° from baseline for the study to be considered optimal. A fourth and final survey was subsequently conducted for confirmation.


Bone & Joint Research
Vol. 12, Issue 8 | Pages 497 - 503
16 Aug 2023
Lee J Koh Y Kim PS Park J Kang K

Aims

Focal knee arthroplasty is an attractive alternative to knee arthroplasty for young patients because it allows preservation of a large amount of bone for potential revisions. However, the mechanical behaviour of cartilage has not yet been investigated because it is challenging to evaluate in vivo contact areas, pressure, and deformations from metal implants. Therefore, this study aimed to determine the contact pressure in the tibiofemoral joint with a focal knee arthroplasty using a finite element model.

Methods

The mechanical behaviour of the cartilage surrounding a metal implant was evaluated using finite element analysis. We modelled focal knee arthroplasty with placement flush, 0.5 mm deep, or protruding 0.5 mm with regard to the level of the surrounding cartilage. We compared contact stress and pressure for bone, implant, and cartilage under static loading conditions.


Bone & Joint Open
Vol. 4, Issue 5 | Pages 363 - 369
22 May 2023
Amen J Perkins O Cadwgan J Cooke SJ Kafchitsas K Kokkinakis M

Aims

Reimers migration percentage (MP) is a key measure to inform decision-making around the management of hip displacement in cerebral palsy (CP). The aim of this study is to assess validity and inter- and intra-rater reliability of a novel method of measuring MP using a smart phone app (HipScreen (HS) app).

Methods

A total of 20 pelvis radiographs (40 hips) were used to measure MP by using the HS app. Measurements were performed by five different members of the multidisciplinary team, with varying levels of expertise in MP measurement. The same measurements were repeated two weeks later. A senior orthopaedic surgeon measured the MP on picture archiving and communication system (PACS) as the gold standard and repeated the measurements using HS app. Pearson’s correlation coefficient (r) was used to compare PACS measurements and all HS app measurements and assess validity. Intraclass correlation coefficient (ICC) was used to assess intra- and inter-rater reliability.


Aims

Classifying trochlear dysplasia (TD) is useful to determine the treatment options for patients suffering from patellofemoral instability (PFI). There is no consensus on which classification system is more reliable and reproducible for the purpose of guiding clinicians’ management of PFI. There are also concerns about the validity of the Dejour Classification (DJC), which is the most widely used classification for TD, having only a fair reliability score. The Oswestry-Bristol Classification (OBC) is a recently proposed system of classification of TD, and the authors report a fair-to-good interobserver agreement and good-to-excellent intraobserver agreement in the assessment of TD. The aim of this study was to compare the reliability and reproducibility of these two classifications.

Methods

In all, six assessors (four consultants and two registrars) independently evaluated 100 axial MRIs of the patellofemoral joint (PFJ) for TD and classified them according to OBC and DJC. These assessments were again repeated by all raters after four weeks. The inter- and intraobserver reliability scores were calculated using Cohen’s kappa and Cronbach’s α.


Bone & Joint Research
Vol. 12, Issue 3 | Pages 212 - 218
9 Mar 2023
Buchalter DB Kirby DJ Anil U Konda SR Leucht P

Aims

Glucose-insulin-potassium (GIK) is protective following cardiac myocyte ischaemia-reperfusion (IR) injury, however the role of GIK in protecting skeletal muscle from IR injury has not been evaluated. Given the similar mechanisms by which cardiac and skeletal muscle sustain an IR injury, we hypothesized that GIK would similarly protect skeletal muscle viability.

Methods

A total of 20 C57BL/6 male mice (10 control, 10 GIK) sustained a hindlimb IR injury using a 2.5-hour rubber band tourniquet. Immediately prior to tourniquet placement, a subcutaneous osmotic pump was placed which infused control mice with saline (0.9% sodium chloride) and treated mice with GIK (40% glucose, 50 U/l insulin, 80 mEq/L KCl, pH 4.5) at a rate of 16 µl/hr for 26.5 hours. At 24 hours following tourniquet removal, bilateral (tourniqueted and non-tourniqueted) gastrocnemius muscles were triphenyltetrazolium chloride (TTC)-stained to quantify percentage muscle viability. Bilateral peroneal muscles were used for gene expression analysis, serum creatinine and creatine kinase activity were measured, and a validated murine ethogram was used to quantify pain before euthanasia.


The Bone & Joint Journal
Vol. 106-B, Issue 5 Supple B | Pages 3 - 10
1 May 2024
Heimann AF Murmann V Schwab JM Tannast M

Aims

The aim of this study was to investigate whether anterior pelvic plane-pelvic tilt (APP-PT) is associated with distinct hip pathomorphologies. We asked: is there a difference in APP-PT between young symptomatic patients being evaluated for joint preservation surgery and an asymptomatic control group? Does APP-PT vary among distinct acetabular and femoral pathomorphologies? And does APP-PT differ in symptomatic hips based on demographic factors?

Methods

This was an institutional review board-approved, single-centre, retrospective, case-control, comparative study, which included 388 symptomatic hips in 357 patients who presented to our tertiary centre for joint preservation between January 2011 and December 2015. Their mean age was 26 years (SD 2; 23 to 29) and 50% were female. They were allocated to 12 different morphological subgroups. The study group was compared with a control group of 20 asymptomatic hips in 20 patients. APP-PT was assessed in all patients based on supine anteroposterior pelvic radiographs using validated HipRecon software. Values in the two groups were compared using an independent-samples t-test. Multiple regression analysis was performed to examine the influences of diagnoses and demographic factors on APP-PT. The minimal clinically important difference (MCID) for APP-PT was defined as > 1 SD.


Bone & Joint Open
Vol. 3, Issue 12 | Pages 953 - 959
23 Dec 2022
Raval P See A Singh HP

Aims

Distal third clavicle (DTC) fractures are increasing in incidence. Due to their instability and nonunion risk, they prove difficult to treat. Several different operative options for DTC fixation are reported but current evidence suggests variability in operative fixation. Given the lack of consensus, our objective was to determine the current epidemiological trends in DTC as well as their management within the UK.

Methods

A multicentre retrospective cohort collaborative study was conducted. All patients over the age of 18 with an isolated DTC fracture in 2019 were included. Demographic variables were recorded: age; sex; side of injury; mechanism of injury; modified Neer classification grading; operative technique; fracture union; complications; and subsequent procedures. Baseline characteristics were described for demographic variables. Categorical variables were expressed as frequencies and percentages.


The Bone & Joint Journal
Vol. 106-B, Issue 5 | Pages 501 - 507
1 May 2024
Galloway AM Keene DJ Anderson A Holton C Redmond AC Siddle HJ Richards S Perry DC

Aims

The aim of this study was to produce clinical consensus recommendations about the non-surgical treatment of children with Perthes’ disease. The recommendations are intended to support clinical practice in a condition for which there is no robust evidence to guide optimal care.

Methods

A two-round, modified Delphi study was conducted online. An advisory group of children’s orthopaedic specialists consisting of physiotherapists, surgeons, and clinical nurse specialists designed a survey. In the first round, participants also had the opportunity to suggest new statements. The survey included statements related to ‘Exercises’, ‘Physical activity’, ‘Education/information sharing’, ‘Input from other services’, and ‘Monitoring assessments’. The survey was shared with clinicians who regularly treat children with Perthes’ disease in the UK using clinically relevant specialist groups and social media. A predetermined threshold of ≥ 75% for consensus was used for recommendation, with a threshold of between 70% and 75% being considered as ‘points to consider’.


Bone & Joint Research
Vol. 13, Issue 2 | Pages 83 - 90
19 Feb 2024
Amri R Chelly A Ayedi M Rebaii MA Aifa S Masmoudi S Keskes H

Aims

The present study investigated receptor activator of nuclear factor kappa-Β ligand (RANKL), osteoprotegerin (OPG), and Runt-related transcription factor 2 (RUNX2) gene expressions in giant cell tumour of bone (GCTB) patients in relationship with tumour recurrence. We also aimed to investigate the influence of CpG methylation on the transcriptional levels of RANKL and OPG.

Methods

A total of 32 GCTB tissue samples were analyzed, and the expression of RANKL, OPG, and RUNX2 was evaluated by quantitative polymerase chain reaction (qPCR). The methylation status of RANKL and OPG was also evaluated by quantitative methylation-specific polymerase chain reaction (qMSP).


Bone & Joint Open
Vol. 5, Issue 5 | Pages 411 - 418
20 May 2024
Schneider P Bajammal S Leighton R Witges K Rondeau K Duffy P

Aims

Isolated fractures of the ulnar diaphysis are uncommon, occurring at a rate of 0.02 to 0.04 per 1,000 cases. Despite their infrequency, these fractures commonly give rise to complications, such as nonunion, limited forearm pronation and supination, restricted elbow range of motion, radioulnar synostosis, and prolonged pain. Treatment options for this injury remain a topic of debate, with limited research available and no consensus on the optimal approach. Therefore, this trial aims to compare clinical, radiological, and functional outcomes of two treatment methods: open reduction and internal fixation (ORIF) versus nonoperative treatment in patients with isolated ulnar diaphyseal fractures.

Methods

This will be a multicentre, open-label, parallel randomized clinical trial (under National Clinical Trial number NCT01123447), accompanied by a parallel prospective cohort group for patients who meet the inclusion criteria, but decline randomization. Eligible patients will be randomized to one of the two treatment groups: 1) nonoperative treatment with closed reduction and below-elbow casting; or 2) surgical treatment with ORIF utilizing a limited contact dynamic compression plate and screw construct. The primary outcome measured will be the Disabilities of the Arm, Shoulder and Hand questionnaire score at 12 months post-injury. Additionally, functional outcomes will be assessed using the 36-Item Short Form Health Survey and pain visual analogue scale, allowing for a comparison of outcomes between groups. Secondary outcome measures will encompass clinical outcomes such as range of motion and grip strength, radiological parameters including time to union, as well as economic outcomes assessed from enrolment to 12 months post-injury.


Bone & Joint Research
Vol. 12, Issue 6 | Pages 387 - 396
26 Jun 2023
Xu J Si H Zeng Y Wu Y Zhang S Shen B

Aims

Lumbar spinal stenosis (LSS) is a common skeletal system disease that has been partly attributed to genetic variation. However, the correlation between genetic variation and pathological changes in LSS is insufficient, and it is difficult to provide a reference for the early diagnosis and treatment of the disease.

Methods

We conducted a transcriptome-wide association study (TWAS) of spinal canal stenosis by integrating genome-wide association study summary statistics (including 661 cases and 178,065 controls) derived from Biobank Japan, and pre-computed gene expression weights of skeletal muscle and whole blood implemented in FUSION software. To verify the TWAS results, the candidate genes were furthered compared with messenger RNA (mRNA) expression profiles of LSS to screen for common genes. Finally, Metascape software was used to perform enrichment analysis of the candidate genes and common genes.