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

Objectives. The most prevalent disorders of the shoulder are related to the muscles of rotator cuff. In order to develop a mechanical method for the evaluation of the rotator cuff muscles, we created a database of isometric force generation by the rotator cuff muscles in normal adult population. We hypothesised the existence of variations according to age, gender and dominancy of limb. Methods. A total of 400 healthy adult volunteers were tested, classified into groups of 50 men and women for each decade of life. Maximal isometric force was measured at standardised positions for supraspinatus, infraspinatus and subscapularis muscles in both shoulders in every person. Torque of the force was calculated and normalised to lean body mass. The profiles of mean torque-time curves for each age and gender group were compared. Results. Our data showed that men gradually gained maximal strength in the fifth decade, and showed decreased strength in the sixth. In women the maximal strength was gained in the fourth decade with gradual decline to the sixth decade of life. The dominant arm was stronger in most of the tested groups. The torque profiles of the rotator cuff muscles in men at all ages were significantly higher than that in women. Conclusions. We found previously unrecognised variations of rotator cuff muscles’ isometric strength according to age, gender and dominancy in a normal population. The presented data may serve as a basis for the future studies for identification of the abnormal patterns of muscle isometric strength in patients with pathology of the rotator cuff muscles. Cite this article: Bone Joint Res 2013;2:214–19

Objectives. Lower limb muscle power is thought to influence outcome following total knee replacement (TKR). Post-operative deficits in muscle strength are commonly reported, although not explained. We hypothesised that post-operative recovery of lower limb muscle power would be influenced by the number of satellite cells in the quadriceps muscle at time of surgery. . Methods. Biopsies were obtained from 29 patients undergoing TKR. Power output was assessed pre-operatively and at six and 26 weeks post-operatively with a Leg Extensor Power Rig and data were scaled for body weight. Satellite cell content was assessed in two separate analyses, the first cohort (n = 18) using immunohistochemistry and the second (n = 11) by a new quantitative polymerase chain reaction (q-PCR) protocol for Pax-7 (generic satellite cell marker) and Neural Cell Adhesion Molecule (NCAM; marker of activated cells). Results. A significant improvement in power output was observed post-operatively with a mean improvement of 19.7 W (95% confidence interval (CI) 14.43 to 30.07; p < 0.001) in the first cohort and 27.5 W (95% CI 13.2 to 41.9; p = 0.002) in the second. A strong correlation was noted between satellite cell number (immunohistochemistry) and improvement in patient power output (r = 0.64, p = 0.008). Strong correlation was also observed between the expression of Pax-7 and power output (r = 0.79, p = 0.004), and the expression of NCAM and power output (r = 0.84, p = 0.001). The generic marker explained 58% of the variation in power output, and the marker of activated cells 67%. Conclusions. Muscle satellite cell content may determine improvement in lower limb power generation (and thus function) following TKR

Aims. Sarcopenia is characterized by a generalized progressive loss of skeletal muscle mass, strength, and physical performance. This systematic review primarily evaluated the effects of sarcopenia on postoperative functional recovery and mortality in patients undergoing orthopaedic surgery, and secondarily assessed the methods used to diagnose and define sarcopenia in the orthopaedic literature. Methods. A systematic search was conducted in MEDLINE, EMBASE, and Google Scholar databases according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines. Studies involving sarcopenic patients who underwent defined orthopaedic surgery and recorded postoperative outcomes were included. The quality of the criteria by which a diagnosis of sarcopenia was made was evaluated. The quality of the publication was assessed using Newcastle-Ottawa Scale. Results. A total of 365 studies were identified and screened, 26 full-texts were reviewed, and 19 studies were included in the review. A total of 3,009 patients were included, of whom 2,146 (71%) were female and 863 (29%) were male. The mean age of the patients was 75.1 years (SD 7.1). Five studies included patients who underwent spinal surgery, 13 included hip or knee surgery, and one involved patients who underwent fixation of a distal radial fixation. The mean follow-up was 1.9 years (SD 1.9; 5 days to 5.6 years). There was wide heterogeneity in the measurement tools which were used and the parameters for the diagnosis of sarcopenia in the studies. Sarcopenia was associated with at least one deleterious effect on surgical outcomes in all 19 studies. The postoperative rate of mortality was reported in 11 studies (57.9%) and sarcopenia was associated with poorer survival in 73% (8/11) of these. The outcome was most commonly assessed using the Barthel Index (4/19), and sarcopenic patients recorded lower scores in 75% (3/4) of these. Sarcopenia was defined using the gold-standard three parameters (muscle strength, muscle quantity or quality, and muscle function) in four studies (21%), using two parameters in another four (21%) and one in the remaining 11 (58%). The methodological quality of the studies was moderate to high. Conclusion. There is much heterogeneity in the reporting of the parameters which are used for the diagnosis of sarcopenia, and evaluating the outcome of orthopaedic surgery in sarcopenic patients. However, what data exist suggest that sarcopenia impairs recovery and increases postoperative mortality, especially in patients undergoing emergency surgery. Further research is required to develop processes that allow the accurate diagnosis of sarcopenia in orthopaedics, which may facilitate targeted pre- and postoperative interventions that would improve outcomes. Cite this article: Bone Joint J 2022;104-B(3):321–330

Aims. Internal hemipelvectomy without reconstruction of the pelvis is a viable treatment for pelvic sarcoma; however, the time it takes to return to excellent function is quite variable. Some patients require greater time and rehabilitation than others. To determine if psoas muscle recovery is associated with changes in ambulatory function, we retrospectively evaluated psoas muscle size and limb-length discrepancy (LLD) before and after treatment and their correlation with objective functional outcomes. Methods. T1-weighted MR images were evaluated at three intervals for 12 pelvic sarcoma patients following interval hemipelvectomy without reconstruction. Correlations between the measured changes and improvements in Timed Up and Go test (TUG) and gait speed outcomes were assessed both independently and using a stepwise multivariate regression model. Results. Increased ipsilesional psoas muscle size from three months postoperatively to latest follow-up was positively correlated with gait speed improvement (r = 0.66). LLD at three months postoperatively was negatively correlated with both TUG (r = -0.71) and gait speed (r = -0.61). Conclusion. This study suggests that psoas muscle strengthening and minimizing initial LLD will achieve the greatest improvements in ambulatory function. LLD and change in hip musculature remain substantial prognostic factors for achieving the best clinical outcomes after internal hemipelvectomy. Changes in psoas size were correlated with the amount of functional improvement. Several patients in this study did not return to their preoperative ipsilateral psoas size, indicating that monitoring changes in psoas size could be a beneficial rehabilitation strategy. Cite this article: Bone Joint J 2023;105-B(3):323–330

The nervous system is known to be involved in inflammation and repair. We aimed to determine the effect of physical activity on the healing of a muscle injury and to examine the pattern of innervation. Using a drop-ball technique, a contusion was produced in the gastrocnemius in 20 rats. In ten the limb was immobilised in a plaster cast and the remaining ten had mobilisation on a running wheel. The muscle and the corresponding dorsal-root ganglia were studied by histological and immunohistochemical methods. In the mobilisation group, there was a significant reduction in lymphocytes (p = 0.016), macrophages (p = 0.008) and myotubules (p = 0.008) between three and 21 days. The formation of myotubules and the density of nerve fibres was significantly higher (both p = 0.016) compared with those in the immobilisation group at three days, while the density of CGRP-positive fibres was significantly lower (p = 0.016) after 21 days. Mobilisation after contusional injury to the muscle resulted in early and increased formation of myotubules, early nerve regeneration and progressive reduction in inflammation, suggesting that it promoted a better healing response

Aims. Rotator cuff (RC) injuries are characterized by tendon rupture, muscle atrophy, retraction, and fatty infiltration, which increase injury severity and jeopardize adequate tendon repair. Epigenetic drugs, such as histone deacetylase inhibitors (HDACis), possess the capacity to redefine the molecular signature of cells, and they may have the potential to inhibit the transformation of the fibro-adipogenic progenitors (FAPs) within the skeletal muscle into adipocyte-like cells, concurrently enhancing the myogenic potential of the satellite cells. Methods. HDACis were added to FAPs and satellite cell cultures isolated from mice. The HDACi vorinostat was additionally administered into a RC injury animal model. Histological analysis was carried out on the isolated supra- and infraspinatus muscles to assess vorinostat anti-muscle degeneration potential. Results. Vorinostat, a HDACi compound, blocked the adipogenic transformation of muscle-associated FAPs in culture, promoting myogenic progression of the satellite cells. Furthermore, it protected muscle from degeneration after acute RC in mice in the earlier muscle degenerative stage after tenotomy. Conclusion. The HDACi vorinostat may be a candidate to prevent early muscular degeneration after RC injury. Cite this article: Bone Joint Res 2024;13(4):169–183

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

Aims. Dystrophic calcification (DC) is the abnormal appearance of calcified deposits in degenerating tissue, often associated with injury. Extensive DC can lead to heterotopic ossification (HO), a pathological condition of ectopic bone formation. The highest rate of HO was found in combat-related blast injuries, a polytrauma condition with severe muscle injury. It has been noted that the incidence of HO significantly increased in the residual limbs of combat-injured patients if the final amputation was performed within the zone of injury compared to that which was proximal to the zone of injury. While aggressive limb salvage strategies may maximize the function of the residual limb, they may increase the possibility of retaining non-viable muscle tissue inside the body. In this study, we hypothesized that residual dead muscle tissue at the zone of injury could promote HO formation. Methods. We tested the hypothesis by investigating the cellular and molecular consequences of implanting devitalized muscle tissue into mouse muscle pouch in the presence of muscle injury induced by cardiotoxin. Results. Our findings showed that the presence of devitalized muscle tissue could cause a systemic decrease in circulating transforming growth factor-beta 1 (TGF-β1), which promoted DC formation following muscle injury. We further demonstrated that suppression of TGF-β signalling promoted DC in vivo, and potentiated osteogenic differentiation of muscle-derived stromal cells in vitro. Conclusion. Taken together, these findings suggest that TGF-β1 may play a protective role in dead muscle tissue-induced DC, which is relevant to understanding the pathogenesis of post-traumatic HO. Cite this article: Bone Joint Res 2020;9(11):742–750

The lower limbs of five cadavers were dissected and the lengths of the muscle fibres and the weights of all the muscles below the knee were measured. From this information the relative strength and excursion of each muscle was determined. We found that the plantarflexors of the ankle were six times as strong as the dorsiflexors. We have therefore discarded the concept of "muscle balance" in tendon transfer surgery and propose that task appropriateness should be the guide. The constant relationship between muscle fibre length and muscle excursion means that contractures are accompanied by decreased excursion. Tendon lengthening improves deformity but does not improve the decreased active range of movement

Aims. Rotational acetabular osteotomy (RAO) is an effective joint-preserving surgical treatment for acetabular dysplasia. The purpose of this study was to investigate changes in muscle strength, gait speed, and clinical outcome in the operated hip after RAO over a one-year period using a standard protocol for rehabilitation. Patients and Methods. A total of 57 patients underwent RAO for acetabular dysplasia. Changes in muscle strength of the operated hip, 10 m gait speed, Japanese Orthopaedic Association (JOA) hip score, and factors correlated with hip muscle strength after RAO were retrospectively analyzed. Results. Three months postoperatively, the strength of the operated hip in flexion and abduction and gait speed had decreased from their preoperative levels. After six months, the strength of flexion and abduction had recovered to their preoperative level, as had gait speed. At one-year follow-up, significant improvements were seen in the strength of hip abduction and gait speed, but muscle strength in hip flexion remained at the preoperative level. The mean JOA score for hip function was 91.4 (51 to 100)) at one-year follow-up. Body mass index (BMI) showed a negative correlation with both strength of hip flexion (r = -0.4203) and abduction (r = -0.4589) one year after RAO. Although weak negative correlations were detected between strength of hip flexion one year after surgery and age (r = -0.2755) and centre-edge (CE) angle (r = -0.2989), no correlation was found between the strength of abduction and age and radiological evaluations of CE angle and acetabular roof obliquity (ARO). Conclusion. Hip muscle strength and gait speed had recovered to their preoperative levels six months after RAO. The clinical outcome at one year was excellent, although the strength of hip flexion did not improve to the same degree as that of hip abduction and gait speed. A higher BMI may result in poorer recovery of hip muscle strength after RAO. Radiologically, acetabular coverage did not affect the recovery of hip muscle strength at one year’s follow-up. A more intensive rehabilitation programme may improve this. Cite this article: Bone Joint J 2019;101-B:1459–1463

Aims. Improvements in the evaluation of outcomes following peripheral nerve injury are needed. Recent studies have identified muscle fatigue as an inevitable consequence of muscle reinnervation. This study aimed to quantify and characterize muscle fatigue within a standardized surgical model of muscle reinnervation. Patients and Methods. This retrospective cohort study included 12 patients who underwent Oberlin nerve transfer in an attempt to restore flexion of the elbow following brachial plexus injury. There were ten men and two women with a mean age of 45.5 years (27 to 69). The mean follow-up was 58 months (28 to 100). Repeated and sustained isometric contractions of the elbow flexors were used to assess fatigability of reinnervated muscle. The strength of elbow flexion was measured using a static dynamometer (KgF) and surface electromyography (sEMG). Recordings were used to quantify and characterize fatigability of the reinnervated elbow flexor muscles compared with the uninjured contralateral side. Results. The mean peak force of elbow flexion was 7.88 KgF (. sd. 3.80) compared with 20.65 KgF (. sd . 6.88) on the contralateral side (p < 0.001). Reinnervated elbow flexor muscles (biceps brachialis) showed sEMG evidence of fatigue earlier than normal controls with sustained (60-second) isometric contraction. Reinnervated elbow flexor muscles also showed a trend towards a faster twitch muscle fibre type. Conclusion. The assessment of motor outcomes must involve more than peak force alone. Reinnervated muscle shows a shift towards fast twitch fibres following reinnervation with an earlier onset of fatigue. Our findings suggest that fatigue is a clinically relevant characteristic of reinnervated muscle. Adoption of these metrics into clinical practice and the assessment of outcome could allow a more meaningful comparison to be made between differing forms of treatment and encourage advances in the management of motor recovery following nerve transfer. Cite this article: Bone Joint J 2019;101-B:867–871

Aims. The aticularis genu (AG) is the least substantial and deepest muscle of the anterior compartment of the thigh and of uncertain significance. The aim of the study was to describe the anatomy of AG in cadaveric specimens, to characterize the relevance of AG in pathological distal femur specimens, and to correlate the anatomy and pathology with preoperative magnetic resonance imaging (MRI) of AG. Methods. In 24 cadaveric specimens, AG was identified, photographed, measured, and dissected including neurovascular supply. In all, 35 resected distal femur specimens were examined. AG was photographed and measured and its utility as a surgical margin examined. Preoperative MRIs of these cases were retrospectively analyzed and assessed and its utility assessed as an anterior soft tissue margin in surgery. In all cadaveric specimens, AG was identified as a substantial structure, deep and separate to vastus itermedius (VI) and separated by a clear fascial plane with a discrete neurovascular supply. Mean length of AG was 16.1 cm ( ± 1.6 cm) origin anterior aspect distal third femur and insertion into suprapatellar bursa. In 32 of 35 pathological specimens, AG was identified (mean length 12.8 cm ( ± 0.6 cm)). Where AG was used as anterior cover in pathological specimens all surgical margins were clear of disease. Of these cases, preoperative MRI identified AG in 34 of 35 cases (mean length 8.8 cm ( ± 0.4 cm)). Results. AG was best visualized with T1-weighted axial images providing sufficient cover in 25 cases confirmed by pathological findings.These results demonstrate AG as a discrete and substantial muscle of the anterior compartment of the thigh, deep to VI and useful in providing anterior soft tissue margin in distal femoral resection in bone tumours. Conclusion. Preoperative assessment of cover by AG may be useful in predicting cases where AG can be dissected, sparing the remaining quadriceps muscle, and therefore function. Cite this article: Bone Joint Open 2020;1-9:585–593

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

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

Objectives. Although many clinical and experimental investigations have shed light on muscle atrophy and intramuscular accumulation of fat after rotator cuff disruption, none have reported on their onset in the absence of muscle retraction. Methods. In 30 rabbits, we detached one supraspinatus (SSP) tendon and repaired it immediately, thus preventing muscle retraction. The animals were killed in groups of 10 at one, two and six weeks. Both shoulders of 15 non-operated rabbits served as controls. We measured the weight and volume of SSP muscles and quantified the cross-sectional area of intramuscular fat (i-fat) histologically. Results. There was significant loss of muscle weight and volume after one week (p = 0.004 and 0.003, respectively), and two weeks (both p < 0.001) in the experimental group; which recovered to control values after six weeks. I-fat accumulated one week after immediate repair, greater than in the control group and statistically significant at the mid-part of the muscle (mean 2.7% vs 1.5%, p = 0.008). I-fat continued to accumulate up to six weeks at all sites of the SSP muscle (all 3, p < 0.001). More fat accumulated closer to the musculotendinous junction than at the mid-part after two and six weeks (p = 0.012 and 0.019, respectively). Conclusion. Muscle atrophy and i-fat accumulation occur early after SSP tendon tear and immediate repair. While early repair benefitted muscle recovery, it did not prevent fat accumulation. SSP muscle retraction was not essential to the muscle alterations. The divergent evolution of muscle and fat points to different pathophysiologies. Cite this article: Bone Joint Res 2014;3:117–22

We retrospectively studied the possibility that direct trauma to the biceps muscle might be the cause of poor elbow flexion and supination in 18 consecutive children with birth lesions of the brachial plexus who had delayed or impaired biceps recovery despite neurophysiological evidence of reinnervation. All had good shoulder and hand function at three months of age. Eight recovered a strong biceps after six months, but nine required a pectoralis minor to biceps transfer to augment elbow flexion and supination. One had a delayed but good recovery of the biceps after microsurgical reconstruction of the plexus. All had a clinical ‘pseudotumour’ in the biceps muscle, which was biopsied during pectoralis minor transfer in two patients and showed rupture and degeneration of muscle fibres with a fibro-fatty infiltrate, suggesting previous muscle trauma. Direct muscle trauma is an uncommon but important cause of delayed or impaired biceps recovery after brachial plexus birth injuries. Surgery to reinnervate the biceps muscle will not work if substantial muscle damage is present when a suitable muscle transfer should be considered

Objectives. The aim of this study was to systematically review the literature on measurement of muscle strength in patients with femoroacetabular impingement (FAI) and other pathologies and to suggest guidelines to standardise protocols for future research in the field. Methods. The Cochrane and PubMed libraries were searched for any publications using the terms ‘hip’, ‘muscle’, ‘strength’, and ‘measurement’ in the ‘Title, Abstract, Keywords’ field. A further search was performed using the terms ‘femoroacetabular’ or ‘impingement’. The search was limited to recent literature only. Results. A total of 29 articles were reviewed to obtain information on a number of variables. These comprised the type of device used for measurement, rater standardisation, the type of movements tested, body positioning and comparative studies of muscle strength in FAI versus normal controls. The studies found that hip muscle strength is lower in patients with FAI; this is also true for the asymptomatic hip in patients with FAI. Conclusions. Current literature on this subject is limited and examines multiple variables. Our recommendations for achieving reproducible results include stabilising the patient, measuring isometric movements and maximising standardisation by using a single tester and familiarising the participants with the protocol. Further work must be done to demonstrate the reliability of any new testing method. Cite this article: E. Mayne, A. Memarzadeh, P. Raut, A. Arora, V. Khanduja. Measuring hip muscle strength in patients with femoroacetabular impingement and other hip pathologies: A systematic review. Bone Joint Res 2017;6:66–72. DOI: 10.1302/2046-3758.61.BJR-2016-0081

Objectives. We have observed clinical cases where bone is formed in the overlaying muscle covering surgically created bone defects treated with a hydroxyapatite/calcium sulphate biomaterial. Our objective was to investigate the osteoinductive potential of the biomaterial and to determine if growth factors secreted from local bone cells induce osteoblastic differentiation of muscle cells. Materials and Methods. We seeded mouse skeletal muscle cells C2C12 on the hydroxyapatite/calcium sulphate biomaterial and the phenotype of the cells was analysed. To mimic surgical conditions with leakage of extra cellular matrix (ECM) proteins and growth factors, we cultured rat bone cells ROS 17/2.8 in a bioreactor and harvested the secreted proteins. The secretome was added to rat muscle cells L6. The phenotype of the muscle cells after treatment with the media was assessed using immunostaining and light microscopy. Results. C2C12 cells differentiated into osteoblast-like cells expressing prominent bone markers after seeding on the biomaterial. The conditioned media of the ROS 17/2.8 contained bone morphogenetic protein-2 (BMP-2 8.4 ng/mg, standard deviation (. sd. ) 0.8) and BMP-7 (50.6 ng/mg, . sd. 2.2). In vitro, this secretome induced differentiation of skeletal muscle cells L6 towards an osteogenic lineage. Conclusion. Extra cellular matrix proteins and growth factors leaking from a bone cavity, along with a ceramic biomaterial, can synergistically enhance the process of ectopic ossification. The overlaying muscle acts as an osteoinductive niche, and provides the required cells for bone formation. Cite this article: D. B. Raina, A. Gupta, M. M. Petersen, W. Hettwer, M. McNally, M. Tägil, M-H. Zheng, A. Kumar, L. Lidgren. Muscle as an osteoinductive niche for local bone formation with the use of a biphasic calcium sulphate/hydroxyapatite biomaterial. Bone Joint Res 2016;5:500–511. DOI: 10.1302/2046-3758.510.BJR-2016-0133.R1

1. The results of a three-year study of recovery in 3,033 lower limb muscles and 1,905 upper limb muscles in 142 patients are presented. 2. The rate of recovery of partly paralysed muscles is the same in all muscles and muscle groups in the lower or upper limb. Clinical differences in the ability of individual muscles to recover depend upon the proportions of their number that remain permanently paralysed. 3. The rate of recovery is slowest in adults and most rapid in young children. 4. The amount of further recovery to be expected in a muscle can be predicted from a knowledge of its grade at any time after one month from the onset of the paralysis. Fourteen-fifteenths of the total amount of recovery takes place by the beginning of the twelfth month; with rare exceptions individual muscle recovery is complete after twenty-four months. 5. Ninety per cent of muscles that are still completely paralysed after six months remain permanently paralysed. 6. The prognosis of a completely paralysed muscle is related to the level of paralysis in muscles supplied by the same spinal segments. 7. Deterioration in power in a muscle is uncommon and, when it occurs, is associated with the presence of the strong opposing force of antagonist muscles or of gravity. 8. The application of these findings to the management of cases of paralytic acute anterior poliomyelitis is discussed