MicroRNAs (miRNAs) are a class of small non-coding RNAs that have emerged as potential predictive, prognostic, and therapeutic biomarkers, relevant to many pathophysiological conditions including limb immobilization, osteoarthritis, sarcopenia, and cachexia. Impaired musculoskeletal homeostasis leads to distinct muscle atrophies. Understanding miRNA involvement in the molecular mechanisms underpinning conditions such as muscle wasting may be critical to developing new strategies to improve patient management. MicroRNAs are powerful post-transcriptional regulators of gene expression in muscle and, importantly, are also detectable in the circulation. MicroRNAs are established modulators of muscle satellite stem cell activation, proliferation, and differentiation, however, there have been limited human studies that investigate miRNAs in muscle wasting. This narrative review summarizes the current knowledge as to the role of miRNAs in the skeletal muscle differentiation and atrophy, synthesizing the findings of published data. Cite this article: Bone Joint Res 2020;9(11):798–807

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. Results. The GMin was smaller in the OA-group (p < 0.001) compared to the control group, but there was no group difference in the size of the GMed (p = 0.101). Higher levels of fatty infiltration were identified in the anterior segment of the GMin (p = 0.006) and the anterior (p = 0.006) and middle (p = 0.047) segments of the GMed in the OA group. All subjects in the control group had fatty infiltration of the anterior segment of the GMin, but all except one had no fatty infiltration in the entire GMed. Conclusion. End-stage OA was associated with significant atrophy of the GMin and higher levels of fatty infiltration, particularly in the anterior segments of the GMin and GMed. Minor fatty infiltration of the anterior segment of GMin appears to be a normal part of ageing. Our study has demonstrated different patterns of atrophy and fatty infiltration between patients with end-stage OA and healthy matched peers. Cite this article: Bone Jt Open 2021;2(1):40–47

Objectives. Nonunion is one of the most troublesome complications to treat in orthopaedics. Former authors believed that atrophic nonunion occurred as a result of lack of mesenchymal stem cells (MSCs). We evaluated the number and viability of MSCs in site of atrophic nonunion compared with those in iliac crest. Methods. We enrolled five patients with neglected atrophic nonunions of long bones confirmed by clinical examinations and plain radiographs into this study. As much as 10 ml bone marrow aspirate was obtained from both the nonunion site and the iliac crest and cultured for three weeks. Cell numbers were counted using a haemocytometer and vitality of the cells was determined by trypan blue staining. The cells were confirmed as MSCs by evaluating their expression marker (CD 105, CD 73, HLA-DR, CD 34, CD 45, CD 14, and CD 19). Cells number and viability were compared between the nonunion and iliac creat sites. Results. After three weeks, numbers of 6.08×10. 6. cells (. sd. 2.07) and 4.98×10. 6. cells (. sd. 1.15) were obtained from the nonunion site and the iliac crest, respectively, with viability of 87.1% (81.7% to 90.8%) and 89.8% (84.7% to 94.5%), respectively. No differences was found between the two sources of MSCs regarding cells number (p = 0.347) and viability (p = 0.175). Conclusions. Our findings showed the existence of MSCs in the site of atrophic nonunion, at a similar number and viability to those isolated from the iliac crest

Objectives. To explore the therapeutic potential of combining bone marrow-derived mesenchymal stem cells (BM-MSCs) and hydroxyapatite (HA) granules to treat nonunion of the long bone. Methods. Ten patients with an atrophic nonunion of a long bone fracture were selectively divided into two groups. Five subjects in the treatment group were treated with the combination of 15 million autologous BM-MSCs, 5g/cm. 3. (HA) granules and internal fixation. Control subjects were treated with iliac crest autograft, 5g/cm. 3. HA granules and internal fixation. The outcomes measured were post-operative pain (visual analogue scale), level of functionality (LEFS and DASH), and radiograph assessment. Results. Post-operative pain evaluation showed no significant differences between the two groups. The treatment group demonstrated faster initial radiographic and functional improvements. Statistically significant differences in functional scores were present during the first (p = 0.002), second (p = 0.005) and third (p = 0.01) month. Both groups achieved similar outcomes by the end of one-year follow-up. No immunologic or neoplastic side effects were reported. Conclusions. All cases of nonunion of a long bone presented in this study were successfully treated using autologous BM-MSCs. The combination of autologous BM-MSCs and HA granules is a safe method for treating nonunion. Patients treated with BM-MSCs had faster initial radiographic and functional improvements. By the end of 12 months, both groups had similar outcomes. Cite this article: H.D. Ismail, P. Phedy, E. Kholinne, Y. P. Djaja, Y. Kusnadi, M. Merlina, N. D. Yulisa. Mesenchymal stem cell implantation in atrophic nonunion of the long bones: A translational study. Bone Joint Res 2016;5:287–293. DOI: 10.1302/2046-3758.57.2000587

Our aim was to develop a clinically relevant model of atrophic nonunion in the rat to test the hypothesis that the vessel density of atrophic nonunion reaches that of normal healing bone, but at a later time-point. Atrophic nonunion is usually attributed to impaired blood supply and is poorly understood. We determined the number of blood vessels at the site of an osteotomy using immunolocalisation techniques in both normally healing bones and in atrophic nonunion. At one week after operation there were significantly fewer blood vessels in the nonunion group than in the healing group. By eight weeks, the number in the atrophic nonunion group had reached the same level as that in the healing group. Our findings suggest that the number of blood vessels in atrophic nonunion reaches the same level as that in healing bone, but at a later time-point. Diminished vascularity within the first three weeks, but not at a later time-point, may prevent fractures from uniting

Aims. Rotator cuff muscle atrophy and fatty infiltration affect the clinical outcomes of rotator cuff tear patients. However, there is no effective treatment for fatty infiltration at this time. High-intensity interval training (HIIT) helps to activate beige adipose tissue. The goal of this study was to test the role of HIIT in improving muscle quality in a rotator cuff tear model via the β3 adrenergic receptor (β3AR). Methods. Three-month-old C57BL/6 J mice underwent a unilateral rotator cuff injury procedure. Mice were forced to run on a treadmill with the HIIT programme during the first to sixth weeks or seventh to 12th weeks after tendon tear surgery. To study the role of β3AR, SR59230A, a selective β3AR antagonist, was administered to mice ten minutes before each exercise through intraperitoneal injection. Supraspinatus muscle, interscapular brown fat, and inguinal subcutaneous white fat were harvested at the end of the 12th week after tendon tear and analyzed biomechanically, histologically, and biochemically. Results. Histological analysis of supraspinatus muscle showed that HIIT improved muscle atrophy, fatty infiltration, and contractile force compared to the no exercise group. In the HIIT groups, supraspinatus muscle, interscapular brown fat, and inguinal subcutaneous white fat showed increased expression of tyrosine hydroxylase and uncoupling protein 1, and upregulated the β3AR thermogenesis pathway. However, the effect of HIIT was not present in mice injected with SR59230A, suggesting that HIIT affected muscles via β3AR. Conclusion. HIIT improved supraspinatus muscle quality and function after rotator cuff tears by activating systemic sympathetic nerve fibre near adipocytes and β3AR. Cite this article: Bone Joint Res 2023;12(8):455–466

Subluxation of the hip is common in patients with intermediate spinal muscular atrophy. This retrospective study aimed to investigate the influence of surgery on pain and function, as well as the natural history of subluxed hips which were treated conservatively. Thirty patients were assessed clinically and radiologically. Of the nine who underwent surgery only one reported satisfaction and four had recurrent subluxation. Of the 21 patients who had no surgery, 18 had subluxation at the latest follow-up, but only one reported pain in the hip. We conclude that surgery for subluxation of the hip in these patients is not justified

Bone weakness leading to refracture is a recognised complication of the removal of rigid fixation plates. We have used partially demineralised rabbit tibiae to simulate atrophic changes and to determine whether weakness is due to atrophy or to residual screw holes. Partial demineralisation and a screw hole each reduced maximum bending moment. However, energy absorbing capacity was little affected by demineralisation, but was reduced to 50% by a single drill hole. Residual screw holes are a considerably more important cause of bone weakness after plate removal than is cortical atrophy

1. The incidence of Sudeck's syndrome in the hand is about once in 2,000 accidents of all kinds. 2. The onset of signs and symptoms occurs some weeks after injury and the typical radiographic changes (spotty atrophy) appear six to eight weeks later. 3. Conservative treatment by heat, elevation and graded function is effective if initiated within six weeks of the onset of symptoms. 4. There is some close relationship between Sudeck's atrophy and thickening of the palmar fascia

The majority of patients with chronic infantile and juvenile forms of spinal muscular atrophy survive to adult life. Forty-four patients have been reviewed at an average of 17 years after diagnosis. The subdivision of patients into four groups, based on the maximal physical function developed by the individual, correlates well with the onset and severity of secondary deformity of the limbs and spine. This information allows anticipation of the problems and plans for their treatment to be made from early childhood. After analysis of the orthotic and surgical treatment received by these patients, a specific programme of care is recommended for each of the functional groups

1. An unusual congenital anomaly of the cervical spine is described. This lesion caused a localised cervical kyphosis and resulted in the development of a mild tetraparesis. 2. The case reported is believed to be the first on record in the English literature of multiple posterior hemivertebrae in the cervical region. 3. The neck deformity was associated with an unusual combination of developmental anomalies–namely, brachyphalangy and bilateral congenital optic atrophy. 4. The importance of differentiating between congenital and acquired causes of kyphosis is emphasised. 5. The radiographic appearances of posterior hemivertebra are described, and the differential diagnosis is considered. 6. The development of the vertebral body, and the relationship between coronal cleft vertebra and posterior hemivertebra, are discussed. The possible role of a disturbance of vascular supply in pathogenesis is mentioned. 7. This report augments the growing literature on congenital skeletal anomalies occurring in combination with isolated congenital ocular defects

Aims. The aim of this study was to describe a quantitative 3D CT method to measure rotator cuff muscle volume, atrophy, and balance in healthy controls and in three pathological shoulder cohorts. Methods. In all, 102 CT scans were included in the analysis: 46 healthy, 21 cuff tear arthropathy (CTA), 18 irreparable rotator cuff tear (IRCT), and 17 primary osteoarthritis (OA). The four rotator cuff muscles were manually segmented and their volume, including intramuscular fat, was calculated. The normalized volume (NV) of each muscle was calculated by dividing muscle volume to the patient’s scapular bone volume. Muscle volume and percentage of muscle atrophy were compared between muscles and between cohorts. Results. Rotator cuff muscle volume was significantly decreased in patients with OA, CTA, and IRCT compared to healthy patients (p < 0.0001). Atrophy was comparable for all muscles between CTA, IRCT, and OA patients, except for the supraspinatus, which was significantly more atrophied in CTA and IRCT (p = 0.002). In healthy shoulders, the anterior cuff represented 45% of the entire cuff, while the posterior cuff represented 40%. A similar partition between anterior and posterior cuff was also found in both CTA and IRCT patients. However, in OA patients, the relative volume of the anterior (42%) and posterior cuff (45%) were similar. Conclusion. This study shows that rotator cuff muscle volume is significantly decreased in patients with OA, CTA, or IRCT compared to healthy patients, but that only minimal differences can be observed between the different pathological groups. This suggests that the influence of rotator cuff muscle volume and atrophy (including intramuscular fat) as an independent factor of outcome may be overestimated. Cite this article: Bone Jt Open 2021;2(7):552–561

The June 2024 Children’s orthopaedics Roundup. 360. looks at: Proximal femoral unicameral bone cysts: is ESIN the answer?; Hybrid-mesh casts in the conservative management of paediatric supracondylar humeral fractures: a randomized controlled trial; Rate and risk factors for contralateral slippage in adolescents treated for slipped capital femoral epiphysis; CRP predicts the need to escalate care after initial debridement for musculoskeletal infection; Genu valgum in paediatric patients presenting with patellofemoral instability; Nusinersen therapy changed the natural course of spinal muscular atrophy type 1: what about spine and hip?; The necessity of ulnar nerve exploration and translocation in open reduction of medial humeral epicondyle fractures in children

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

Aims. The aim of this study was to analyse human muscle tissue before and after rotator cuff repair to look for evidence of regeneration, and to characterise the changes seen in the type of muscle fibre. Patients and Methods. Patients were assessed pre-operatively and one year post-operatively using the Oxford Shoulder Score (OSS) and MRI. The cross-sectional area and distribution of the type of muscle fibre were assessed on biopsies, which were taken at surgery and one year post-operatively. Paired samples from eight patients were analysed. There were three men and five women with a mean age of 63 years (50 to 73). Results. All but one patient showed improvement in OSS (p = 0.004). The mean increase in the cross-sectional area of the muscle was 1220 μm. 2. (-801 to 3712; p = 0.03). There was a reduction of type 2a fibres (p = 0.02). A clear relationship could not be seen between the MRI findings and the histological appearances. Conclusion. This is the first study to provide evidence that atrophy of the supraspinatus muscle is reversible. Changes in the types of fibre are discussed. MRI assessment of muscle atrophy may not be fully representative of myofibre atrophy. Cite this article: Bone Joint J 2016;98-B:1389–94

Aims. The main aims were to identify risk factors predictive of a radiolucent line (RLL) around the acetabular component with an interface bioactive bone cement (IBBC) technique in the first year after THA, and evaluate whether these risk factors influence the development of RLLs at five and ten years after THA. Methods. A retrospective review was undertaken of 980 primary cemented THAs in 876 patients using cemented acetabular components with the IBBC technique. The outcome variable was any RLLs that could be observed around the acetabular component at the first year after THA. Univariate analyses with univariate logistic regression and multivariate analyses with exact logistic regression were performed to identify risk factors for any RLLs based on radiological classification of hip osteoarthritis. Results. RLLs were detected in 27.2% of patients one year postoperatively. In multivariate regression analysis controlling for confounders, atrophic osteoarthritis (odds ratio (OR) 2.17 (95% confidence interval (CI), 1.04 to 4.49); p = 0.038) and 26 mm (OR 3.23 (95% CI 1.85 to 5.66); p < 0.001) or 28 mm head diameter (OR 3.64 (95% CI 2.07 to 6.41); p < 0.001) had a significantly greater risk for any RLLs one year after surgery. Structural bone graft (OR 0.19 (95% CI 0.13 to 0.29) p < 0.001) and location of the hip centre within the true acetabular region (OR 0.15 (95% CI 0.09 to 0.24); p < 0.001) were significantly less prognostic. Improvement of the cement-bone interface including complete disappearance and poorly defined RLLs was identified in 15.1% of patients. Kaplan-Meier survival analysis for the acetabular component at ten years with revision of the acetabular component for aseptic loosening as the end point was 100.0% with a RLL and 99.1% without a RLL (95% CI 97.9 to 100). With revision of the acetabular component for any reason as the end point, the survival rate was 99.2% with a RLL (95% CI 97.6 to 100) and 96.5% without a RLL (95% CI 93.4 to 99.7). Conclusion. This study demonstrates that acetabular bone quality, head diameter, structural bone graft, and hip centre position may influence the presence of the any RLL. Cite this article: Bone Joint Open 2021;2(5):278–292

The original forged Müller straight stem (CoNiCr) has shown excellent ten- to 15-year results. We undertook a long-term survival analysis with special emphasis on radiological changes within a 20-year period of follow-up. In all, 165 primary total hip replacements, undertaken between July 1984 and June 1987 were followed prospectively. Clinical follow-up included a standardised clinical examination, and radiological assessment was based on a standardised anteroposterior radiograph of the pelvis, which was studied for the presence of osteolysis, debonding and cortical atrophy. Survival of the stem with revision for any reason was 81% (95% confidence interval (CI), 76 to 86) at 20 years and for aseptic loosening 87% (95% CI, 82 to 90). At the 20-year follow-up, 15 of the surviving 36 stems showed no radiological changes. Debonding (p = 0.005), osteolysis (p = 0.003) and linear polyethylene wear (p = 0.016) were associated with aseptic loosening, whereas cortical atrophy was not associated with failure (p = 0.008). The 20-year results of the Müller straight stem are comparable to those of other successful cemented systems with similar follow-up. Radiological changes are frequently observed, but with a low incidence of progression, and rarely result in revision. Cortical atrophy appears to be an effect of ageing and not a sign of loosening of the femoral component

Aims. To report the mid-term results of a modified self-growing rod (SGR) technique for the treatment of idiopathic and neuromuscular early-onset scoliosis (EOS). Methods. We carried out a retrospective analysis of 16 consecutive patients with EOS treated with an SGR construct at a single hospital between September 2008 and December 2014. General demographics and deformity variables (i.e. major Cobb angle, T1 to T12 length, T1 to S1 length, pelvic obliquity, shoulder obliquity, and C7 plumb line) were recorded preoperatively, and postoperatively at yearly follow-up. Complications and revision procedures were also recorded. Only patients with a minimum follow-up of five years after surgery were included. Results. A total of 16 patients were included. Six patients had an idiopathic EOS while ten patients had a neuromuscular or syndromic EOS (seven spinal muscular atrophy (SMA) and three with cerebral palsy or a syndrome). Their mean ages at surgery were 7.1 years (SD 2.2) and 13.3 years (SD 2.6) respectively at final follow-up. The mean preoperative Cobb angle of the major curve was 66.1° (SD 8.5°) and had improved to 25.5° (SD 9.9°) at final follow-up. The T1 to S1 length increased from 289.7 mm (SD 24.9) before surgery to 330.6 mm (SD 30.4) immediately after surgery. The mean T1 to S1 and T1 to T12 growth after surgery were 64.1 mm (SD 19.9) and 47.4 mm (SD 18.8), respectively, thus accounting for a mean T1 to S1 and T1 to T12 spinal growth after surgery of 10.5 mm/year (SD 3.7) and 7.8 mm/year (SD 3.3), respectively. A total of six patients (five idiopathic EOS, one cerebral palsy EOS) had broken rods during their growth spurt but were uneventfully revised with a fusion procedure. No other complications were noted. Conclusion. Our data show that SGR is a safe and effective technique for the treatment of EOS in nonambulatory hypotonic patients with a neuromuscular condition. Significant spinal growth can be expected after surgery and is comparable to other published techniques for EOS. While satisfactory correction of the deformity can be achieved and maintained with this technique, a high rate of rod breakage was seen in patients with an idiopathic or cerebral palsy EOS. Cite this article: Bone Joint J 2020;102-B(11):1560–1566

Objectives . Rotator cuff tears are among the most common and debilitating upper extremity injuries. Chronic cuff tears result in atrophy and an infiltration of fat into the muscle, a condition commonly referred to as ‘fatty degeneration’. While stem cell therapies hold promise for the treatment of cuff tears, a suitable immunodeficient animal model that could be used to study human or other xenograft-based therapies for the treatment of rotator cuff injuries had not previously been identified. Methods . A full-thickness, massive supraspinatus and infraspinatus tear was induced in adult T-cell deficient rats. We hypothesised that, compared with controls, 28 days after inducing a tear we would observe a decrease in muscle force production, an accumulation of type IIB fibres, and an upregulation in the expression of genes involved with muscle atrophy, fibrosis and inflammation. Results . Chronic cuff tears in nude rats resulted in a 30% to 40% decrease in muscle mass, a 23% reduction in production of muscle force, and an induction of genes that regulate atrophy, fibrosis, lipid accumulation, inflammation and macrophage recruitment. Marked large lipid droplet accumulation was also present. Conclusions . The extent of degenerative changes in nude rats was similar to what was observed in T-cell competent rats. T cells may not play an important role in regulating muscle degeneration following chronic muscle unloading. The general similarities between nude and T-cell competent rats suggest the nude rat is likely an appropriate preclinical model for the study of xenografts that have the potential to enhance the treatment of chronically torn rotator cuff muscles. Cite this article: Bone Joint Res 2014;3:262–72