Search

Abstract Background Sarcopenia is a prevalent muscle disorder in old people leading to higher fracture rate, mortality, and other adverse clinical outcomes. Evidence indicates that short‐chain fatty acids (SCFAs), which are beneficial gut microbial metabolites, were reduced in old people with sarcopenia. This study aimed to determine whether the use of SCFAs as a supplement can be a therapeutic strategy of sarcopenia in a pre‐clinical model. Methods Seven‐month‐old pre‐sarcopenic senescent accelerated mouse prone 8 (SAMP8) mice received daily SCFAs cocktail (acetate, butyrate, and propionate) for 3 months. Age‐matched senescence accelerated mouse resistant 1 (SAMR1) and SAMP8 mice receiving sodium‐matched drinking water were control groups. The gut microbiota composition analysis of aged mice with or without sarcopenia was conducted by 16S rDNA sequencing. Gut barrier‐related proteins and lipopolysaccharide (LPS) concentration were biomarkers of gut permeability. Colon inflammation levels, circulatory SCFAs concentration, muscle quality, function, and underlying pathways were detected by cell number counting, RT‐qPCR, gas chromatography–mass spectrometry, measurements of muscle wet weight and grip strength, ex vivo functional test, treadmill endurance test, transcriptomic sequencing, morphological and immunofluorescent staining, as well as western blot. To investigate the role of mTOR signalling pathways in SCFAs treatment, C2C12 myotubes were treated with rapamycin. Results Aged SAMP8 mice had different microbiota composition, and lower serum butyric acid compared with SAMR1 mice (P

Background: Hip fractures are one of the most serious forms of fragility fractures. Low-magnitude high-frequency vibration (LMHFV) is a biophysical intervention that provides non-invasive, systemic mechanical stimulation. The objectives of this study were to investigate the efficacy of LMHFV in trochanteric hip fracture elderly patients to (i) accelerate trochanteric fracture healing and (ii) improve clinical and functional outcomes. Methods: A randomized double-blinded, placebo-controlled clinical trial was conducted. Participants were randomly assigned into LMHFV or placebo intervention for 14 days. Primary outcome assessments were fracture healing assessed with CT scan and X-rays. Dual X-ray Absorptiometry (DXA) scan was performed to assess bone mineral density change. Secondary outcome assessments were clinical and functional outcomes with quadriceps muscle strength, balancing ability, handgrip strength, Time Up and Go (TUG) test, quality of life outcomes, pain, falls, and mortality. Results: 237 patients were screened for eligibility by the inclusion and exclusion criteria. 62 patients were recruited and randomly assigned to placebo group (n = 32, mean age: 83.6 ± 7.0 years, women: 71.9 %) or LMHFV group (n = 30, mean age: 81.5 ± 5.7 years, women: 73.3 %). For fracture healing, CT scan at 6 weeks showed improved osseous union for the LMHFV group at 71.5 ± 19.4 % compared to placebo group at 58.8 ± 30.5 %, but no statistical significance detected. X-rays showed fractures healed at 12 months. LMHFV group had significantly higher quadriceps muscle strength compared to placebo group on affected leg using maximum reading (week 26: 8.8 ± 3.6 kg vs. 6.1 ± 4.1 kg; p = 0.011) and average reading (week 26: 8.0 ± 3.7 kg vs. 5.2 ± 3.3 kg; p = 0.008) amongst 3 trials. The balancing ability test could not be performed in most of the subjects at the baseline measurement. However, from week 6 to week 26, LMHFV group had significantly improved balancing compared to placebo group for overall stability index (week 26: 1.6 ± 1.1 vs. 3.4 ± 2.6; p = 0.006), anteroposterior stability index (week 26: 1.1 ± 0.7 vs. 2.1 ± 1.9; p = 0.048) and medial-lateral stability index (week 26: 0.9 ± 0.7 vs. 2.2 ± 2.2; p = 0.008). There was a significant increase in success in performing TUG test in LMHFV group from baseline (13.3 %) to 26 weeks (57.1 %) (p = 0.004). Quality-of-life outcomes by SF-36 showed LMHFV group had a significant improvement at a score of 62.1 ± 18.9 compared to control group at a score of 48.5 ± 18.9 after adjusting for the baseline measurement (p = 0.044). Conclusion: A short duration of LMHFV during in-patient stay can improve clinical outcomes and can potentially be incorporated as a practical measure during the recovery of fragility hip fractures. The translational potential of this article: 14 days of LMHFV treatment is generally within the common in-patient stay period for hip fracture patients and therefore can potentially be incorporated into clinical practice with physiotherapy to facilitate recovery of hip fracture patients. Clinical trial registration number: NCT04063891.

Background: Romosozumab is a novel monoclonal antibody that binds to sclerostin, and has dual effects of increasing bone formation and decreasing bone resorption, giving it a unique mechanism of action. The objective of this study was to perform a systematic review and meta-analysis based on existing worldwide data on treatment effects and safety of romosozumab in randomized controlled trials. Methods: A systematic search was carried out on four databases including PubMed, Embase, Web of Science and Cochrane Central Register of Controlled Trials (CENTRAL). The keywords used for search was “(romosozumab) AND (osteoporosis OR safety)”. Randomized controlled trial or post-hoc studies of the included randomized controlled trial which studied the effects and safety of romosozumab were included. The quality of selected studies was assessed with the Cochrane collaboration tool and the PEDro scale. Results: 20 studies were included for qualitative analysis. 14 studies were included for meta-analysis. In total, there were 13,507 (n = 13,507) participants with 637 men and 12,870 women from original cohorts. The overall mean difference was in favor of romosozumab treatment for lumbar spine (10.04 (95 % confidence interval (CI) = 7.51–12.57; p

Abstract Background This study introduced an Augmented Reality (AR) navigation system to address limitations in conventional high tibial osteotomy (HTO). The objective was to enhance precision and efficiency in HTO procedures, overcoming challenges such as inconsistent postoperative alignment and potential neurovascular damage. Methods The AR-MR (Mixed Reality) navigation system, comprising HoloLens, Unity Engine, and Vuforia software, was employed for pre-clinical trials using tibial sawbone models. CT images generated 3D anatomical models, projected via HoloLens, allowing surgeons to interact through intuitive hand gestures. The critical procedure of target tracking, essential for aligning virtual and real objects, was facilitated by Vuforia’s feature detection algorithm. Results In trials, the AR-MR system demonstrated significant reductions in both preoperative planning and intraoperative times compared to conventional navigation and metal 3D-printed surgical guides. The AR system, while exhibiting lower accuracy, exhibited efficiency, making it a promising option for HTO procedures. The preoperative planning time for the AR system was notably shorter (4 min) compared to conventional navigation (30.5 min) and metal guides (75.5 min). Intraoperative time for AR lasted 8.5 min, considerably faster than that of conventional navigation (31.5 min) and metal guides (10.5 min). Conclusions The AR navigation system presents a transformative approach to HTO, offering a trade-off between accuracy and efficiency. Ongoing improvements, such as the incorporation of two-stage registration and pointing devices, could further enhance precision. While the system may be less accurate, its efficiency renders it a potential breakthrough in orthopedic surgery, particularly for reducing unnecessary harm and streamlining surgical procedures.

Abstract Sarcopenia is a complex age-associated syndrome of progressive loss of muscle mass and strength. Although this condition is influenced by many factors, age-related changes in immune function including immune cell dynamics, and chronic inflammation contribute to its progression. The complex interplay between the immune system, gut-muscle axis, and autophagy further underscores their important roles in sarcopenia pathogenesis. Immunomodulation has emerged as a promising strategy to counteract sarcopenia. Traditional management approaches to treat sarcopenia including physical exercise and nutritional supplementation, and the emerging technologies of biophysical stimulation demonstrated the importance of immunomodulation and regulation of macrophages and T cells and reduction of chronic inflammation. Treatments to alleviate low-grade inflammation in older adults by modulating gut microbial composition and diversity further combat sarcopenia. Furthermore, some pharmacological interventions, nano-medicine, and cell therapies targeting muscle, gut microbiota, or autophagy present additional avenues for immunomodulation in sarcopenia. This narrative review explores the immunological underpinnings of sarcopenia, elucidating the relationship between the immune system and muscle during ageing. Additionally, the review discusses new areas such as the gut-muscle axis and autophagy, which bridge immune system function and muscle health. Insights into current and potential approaches for sarcopenia management through modulation of the immune system are provided, along with suggestions for future research directions and therapeutic strategies. We aim to guide further investigation into clinical immunological biomarkers and identify indicators for sarcopenia diagnosis and potential treatment targets to combat this condition. We also aim to draw attention to the importance of considering immunomodulation in the clinical management of sarcopenia.

Background: The interaction between muscle and bone is shown to be clinically important but the underlying mechanisms are largely unknown. The canonical Wnt/β-catenin signaling pathway is reported to be involved in muscle-bone crosstalk, but its detailed function remains unclear. This systematic review aims to investigate and elucidate the role of the Wnt/β-catenin signaling pathways in muscle-bone crosstalk. Methods: We conducted a literature search on the Web of Science, PubMed, EBSCO and Embase with keywords “Wnt*”, “bone*” and “muscle*”. A systematic review was completed according to the guideline of preferred reporting items of systematic reviews and meta-analyses (PRISMA). Data synthesis included species (human, animal or cell type used), treatments involved, outcome measures and key findings with respect to Wnts. Results: Seventeen papers were published from 2007 to 2021 and were extracted from a total of 1529 search results in the databases of Web of Science (468 papers), PubMed (457 papers), EBSCO (371) and Embase (233). 12 Wnt family members were investigated in the papers, including Wnt1, Wnt2, Wnt2b, Wnt3a, Wnt4, Wnt5a, Wnt8a, Wnt8b, Wnt9a, Wnt10a, Wnt10b and Wnt16. Many studies showed that muscles were able to increase or decrease osteogenesis of bone, while bone increased myogenesis of muscle through Wnt/β-catenin signaling pathways. Wnt3a, Wnt4 and Wnt10b were shown to play important roles in the crosstalk between muscle and bone. Conclusions: Wnt3a, Wnt4 and Wnt10b are found to play important mediatory roles in muscle-bone crosstalk. The role of Wnt4 was mostly found to regulate muscle from the bone side. Whilst the role of Wnt10b during muscle ageing was proposed, current evidence is insufficient to clarify the specific role of Wnt/β-catenin signaling in the interplay between sarcopenia and osteoporosis. More future studies are required to investigate the exact regulatory roles of Wnts in muscle-bone crosstalk in musculoskeletal disease models such as sarcopenia and osteoporosis. Translational potential of this article: The systematic review provides an extensive overview to reveal the roles of Wnt/β-catenin signaling pathways in muscle-bone crosstalk. These results provide novel research directions to further understand the underlying mechanism of sarcopenia, osteoporosis, and their crosstalk, finally helping the future development of new therapeutic interventions.

The neuromuscular junction (NMJ) is a specialized chemical synapse that converts neural impulses into muscle action. Age-associated NMJ degeneration, which involves nerve terminal and postsynaptic decline, denervation, and loss of motor units, significantly contributes to muscle weakness and dysfunction. Although physical training has been shown to make substantial modifications in NMJ of both young and aged animals, the results are often influenced by methodological variables in existing studies. Moreover, there is still lack of strong consensus on the specific effects of exercise on improving the morphology and function of the ageing NMJ. Consequently, the purpose of this study was to conduct a systematic review to elucidate the effects of exercise training on NMJ compartments in the elderly.We conducted a systematic review using PubMed, Embase, and Web of Science databases, employing relevant keywords. Two independent reviewers selected studies that detailed NMJ changes during exercise in ageing, written in English, and available in full text.In total, 20 papers were included. We examined the altered adaptation of the NMJ to exercise, focusing on presynaptic and postsynaptic structures and myofibers in older animals or humans. Our findings indicated that aged NMJs exhibited different adaptive responses to physical exercise compared to younger counterparts. Endurance training, compared with resistance and voluntary exercise regimens, was found to have a more pronounced effect on NMJ structural remodeling, particularly in fast twitch muscle fibers. Physical exercise was observed to promote the formation and maintenance of acetylcholine receptor (AChR) clusters by increasing the recombinant docking protein 7 (Dok7) expression and stabilizing Agrin and lipoprotein receptor-related protein 4 (LRP4). These insights suggest that research on exercise-related therapies could potentially attenuate the progression of neuromuscular degeneration.Translational potential of this article: This systematic review provides a detailed overview of the effects of different types of physical exercise on improving NMJ in the elderly, providing scientific support for the timely intervention of muscle degeneration in the elderly by physical exercise, and providing help for the development of new therapeutic interventions in the future.

Objective: Fracture-related infection (FRI) remains a major concern in orthopaedic trauma. Functionalizing implants with antibacterial coatings are a promising strategy in mitigating FRI. Numerous implant coatings have been reported but the preventive and therapeutic effects vary. This systematic review aimed to provide a comprehensive overview of current implant coating strategies to prevent and treat FRI in animal fracture and bone defect models. Methods: A literature search was performed in three databases: PubMed, Web of Science and Embase, with predetermined keywords and criteria up to 28 February 2023. Preclinical studies on implant coatings in animal fracture or defect models that assessed antibacterial and bone healing effects were included. Results: A total of 14 studies were included in this systematic review, seven of which used fracture models and seven used defect models. Passive coatings with bacteria adhesion resistance were investigated in two studies. Active coatings with bactericidal effects were investigated in 12 studies, four of which used metal ions including Ag+ and Cu2+; five studies used antibiotics including chlorhexidine, tigecycline, vancomycin, and gentamicin sulfate; and the other three studies used natural antibacterial materials including chitosan, antimicrobial peptides, and lysostaphin. Overall, these implant coatings exhibited promising efficacy in antibacterial effects and bone formation. Conclusion: Antibacterial coating strategies reduced bacterial infections in animal models and favored bone healing in vivo. Future studies of implant coatings should focus on optimal biocompatibility, antibacterial effects against multi-drug resistant bacteria and polymicrobial infections, and osseointegration and osteogenesis promotion especially in osteoporotic bone by constructing multi-functional coatings for FRI therapy. The translational potential of this paper: The clinical treatment of FRI is complex and challenging. This review summarizes novel orthopaedic implant coating strategies applied to FRI in preclinical studies, and offers a perspective on the future development of orthopaedic implant coatings, which can potentially contribute to alternative strategies in clinical practice.

Introduction: The COVID-19 pandemic has caused high mortality rates in hip fracture patients, but data for Asian patients are lacking. Whilst Cycle threshold (Ct) values and D-dimer have been reported as predictors of mortality in COVID-19 patients, their prognostic roles in those with concomitant hip fracture remain unknown. The objectives of this study were to i) assess the clinical outcomes of COVID-19 hip fractures patients in the Chinese population, ii) identify risk factors of mortality and complications, and iii) determine the prognostic roles of Ct values and D-dimer levels. Methodology: This cohort study was conducted during the 5th wave of the COVID-19 pandemic. Inclusion criteria were 1) hip fracture 2) ​≥ ​60 years old 3) low-energy trauma. Outcomes were 90-day all-cause mortality, complications, length of stay, discharge destination and mobility status. Logistic regression analysis was performed to identify risk factors for mortality and complications. Subgroup analysis was performed for patients with Ct ​ ​30, comparing their outcomes of operations performed within 48 ​h vs beyond 48 ​h. Results: 159 hip fracture patients were included, 42 patients were COVID-19 positive. COVID-19 group had significantly higher 90-day mortality rates (21.4% vs 9.4%), complication rates (45.2% vs 28.2%) and longer length of stay (17.06 vs 10.84 nights). COVID-19 was an independent risk factor for mortality and complications. Amongst the COVID-19 group, risk factors for poor outcomes were advanced age, steroids use, conservative treatment and American Society of Anaesthesiologists (ASA) score ≥ 3. Conservative treatment was associated with higher mortality (OR ​= ​16.00; p ​= ​0.025) in COVID-19 hip fracture patients. There was no significant difference between Ct values ​30 regarding mortality and complication rate. D-dimer and timing to operation did not affect outcomes. Conclusions: Patients with concomitant COVID-19 and hip fracture are at high risk of mortality and complications. Ct values and D-dimer levels have no prognostic roles for hip fracture outcomes. Early operative treatment is recommended as soon as patients are medically fit.

Introduction Sarcopenia is characterised by age-related loss of skeletal muscle and function and is associated with risks of adverse outcomes. The prevalence of sarcopenia increases due to ageing population and effective interventions is in need. Previous studies showed that β-hydroxy β-methylbutyrate (HMB) supplement and vibration treatment (VT) enhanced muscle quality, while the coapplication of the two interventions had further improved muscle mass and function in sarcopenic mice model. This study aims to investigate the efficacy of this combination treatment in combating sarcopenia in older people. The findings of this study will demonstrate the effect of combination treatment as an alternative for managing sarcopenia.Methods and analysis In this single-blinded randomised controlled trial, subjects will be screened based on the Asian Working Group for Sarcopenia (AWGS) 2019 definition. 200 subjects who are aged 65 or above and identified sarcopenic according to the AWGS algorithm will be recruited. They will be randomised to one of the following four groups: (1) Control+ONS; (2) HMB+ONS; (3) VT+ONS and (4) HMB+VT + ONS, where ONS stands for oral nutritional supplement. ONS will be taken in the form of protein formular once/day; HMB supplements will be 3 g/day; VT (35 Hz, 0.3 g, where g=gravitational acceleration) will be received for 20 mins/day and at least 3 days/week. The primary outcome assessments are muscle strength and function. Subjects will be assessed at baseline, 3-month and 6-month post treatment.Ethics and dissemination This study was approved by Joint CUHK-NTEC (The Chinese University of Hong Kong and New Territories East Cluster) Clinical Research Management Office (Ref: CRE-2022.223-T) and conformed to the Declaration of Helsinki. Trial results will be published in peer-reviewed journals and disseminated at academic conferences.Trial registration number NCT05525039.

Background: Cognitive impairment is a major challenge for elderlies, as it can progress in a rapid manner and effective treatments are limited. Sarcopenic elderlies have a higher risk of dementia. This scoping review aims to reveal whether muscle is a mediator of cognitive function from pre-clinical evidence. Methods: PubMed, Embase, and Web of Science were searched to Feb 2nd, 2022, using the keywords (muscle) AND (cognition OR dementia OR Alzheimer) AND (mouse OR rat OR animal). The PRISMA guideline was used in this study. Results: A total of 17 pre-clinical studies were selected from 7638 studies. 4 studies reported that muscle atrophy and injury harmed memory, functional factors, and neurons in the brain for rodents with or without Alzheimer's disease (AD). 3 studies observed exercise induced muscle to secrete factors, including lactate, fibronectin type III domain-containing protein 5 (FNDC5), and cathepsin B, which plays essential roles in the elevation of cognitive functions and brain-derived neurotrophic factor (BDNF) levels. Muscle-targeted treatments including electrical stimulation and intramuscular injections had effective remote effects on the hippocampus. 6 studies showed that muscle-specific overexpression of scFv59 and Neprilysin, or myostatin knockdown alleviated AD symptoms. 1 study showed that muscle insulin resistance also led to deficient hippocampal neurogenesis in MKR mice. Conclusions: The skeletal muscle is involved in the mediation of cognitive function. The evidence was established by the response in the brain (altered number of neurons, functional factors, and other AD pathological characteristics) with muscle atrophy or injury, muscle secretory factors, and muscle-targeted treatments. The translational potential of this paper: This study summarizes the current evidence in how muscle affects cognition in molecular levels, which supports muscle-specific treatments as potential clinical strategies to prevent cognitive dysfunction.

Osteoporosis is a systemic skeletal disease where there is low bone mass and deterioration of bone microarchitecture, leading to an increased risk of a fragility fracture. The aim of this clinical guideline from Fragility Fracture Network Hong Kong SAR, is to provide evidence-based recommendations on the post-acute treatment of the osteoporotic fracture patient that presents for clinical care at the Fracture Liaison Service (FLS). It is now well established that the incidence of a second fracture is especially high after the first 2 years of the initial osteoporotic fracture. Therefore, the recent osteoporotic fracture should be categorized as “very-high” re-fracture risk. Due to the significant number of silent vertebral fractures in the elderly population, it is also recommended that vertebral fracture assessment (VFA) should be incorporated into FLS. This would have diagnostic and treatment implications for the osteoporotic fracture patient. The use of a potent anti-osteoporotic agent, and preferably an anabolic followed by an anti-resorptive agent should be considered, as larger improvements in BMD is strongly associated with a reduction in fractures. Managing other risk factors including falls and sarcopenia are imperative during rehabilitation and prevention of another fracture. Although of low incidence, one should remain vigilant of the atypical femoral fracture. The aging population is increasing worldwide, and it is expected that the treatment of osteoporotic fractures will be routine. The recommendations are anticipated to aid in the daily clinical practice for clinicians. The Translational potential of this article: Fragility fractures have become a common encounter in clinical practise in the hospital setting. This article provides recommendations on the post-acute management of fragility fracture patients at the FLS.

Background: All fracture repairs start with the innate immune system with the inflammatory response known as the inflammatory stage guided and driven by the secretion of chemokine by the ruptured tissue, followed by the sequential recruitment of neutrophils, monocytes and macrophages. These innate immune cells would infiltrate the fracture site and secrete inflammatory cytokines to stimulate recruitment of more immune cells to arrive at the fracture site coordinating subsequent stages of the repair process. In which, subsidence of pro-inflammatory M1 macrophage and transformation to anti-inflammatory M2 macrophages promotes osteogenesis that marks the start of the anabolic endochondral stage. Methods: Literature search was performed on Pubmed, Embase, and Web of Science databases (last accessed 15th April 2021) using “macrophage AND fracture”. Review was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline. Results: Eleven pre-clinical animal studies out of 429 articles were included in this systematic review according to our inclusion and exclusion criteria. All of which investigated interventions targeting to modulate the acute inflammatory response and macrophage polarization as evident by various markers in association with fracture healing outcomes. Conclusion: This systematic review summarizes attempts to modulate the innate immune response with focuses on promoting macrophage polarization from M1 to M2 phenotype targeting the enhancement of fracture injury repair. Methods used to achieve the goal may include applications of damage-associated molecular pattern (DAMP), pathogen-associated molecular pattern (PAMP) or mechanical stimulation that hold high translational potentials for clinical application in the near future.

Background: Sarcopenia is a hallmark of the ageing process, which is characterized by the decline in muscle mass and strength. Growing evidence indicates that mitochondria dysfunction play core roles in this process. Meanwhile, physical exercise is regarded as one of the efficiency therapies to attenuate sarcopenia via regulating mitochondrial function during ageing. However, the specific mechanisms among exercise, mitochondrial function and sarcopenia are still unclear. The aim of this systematic review is to delineate the effects of physical exercise on mitochondria during ageing in order to explore potential target for rescuing sarcopenia. Methods: A systematic literature search was performed in PubMed, Embase and Web of Science. Information was extracted from the included studies for review. Results: In this review, 16 pre-clinical studies were included and 105 clinical studies that were not mechanistic research were excluded. 16 pre-clinical studies provided evidence that physical exercise could affect mitochondrial quality control to attenuate sarcopenia. Most of the included studies described the important role of mitochondrial dynamic equilibrium in sarcopenia and showed that effective physical exercise could influence mitochondrial biogenesis, fusion, fission and mitophagy to attenuate sarcopenia in aged animal. Conclusions: This systematic review provides an up-to-date sequential overview and highlights the link in the potential mitochondria-related target and physical exercise in aged animal. Translation of this article: Currently, there is no standard treatment method for sarcopenia. This systematic review revealed the underlying mechanisms for how physical exercise improved muscle performance via regulating mitochondrial dynamic equilibrium, which could provide scientific support for using exercise as a timely intervention for sarcopenia. Additionally, this systematic review allows a better understanding of mitochondrial dynamic equilibrium and exercise for future development of new therapeutic interventions to attenuate sarcopenia.

Abstract The incidence of geriatric hip fractures continues to rise in our aging population and has become a major public health concern globally. The primary outcome of this study was to determine whether Age-adjusted Charlson Comorbidity Index (ACCI) is associated with increased fracture-related complications in neck of femur fractures treated by internal fixation. This was a cohort study between January 2014 to June 2018. All patients ≥ 50 years old with an acute neck of femur fracture after low-energy trauma fixed with cannulated hip screws were included and followed-up for 1 year at a tertiary centre. Primary outcome was to determine whether ACCI was associated with increased fracture-related complications. Secondary outcomes were revision rate, mortality, and function after surgery. Further analysis were performed within a “younger” group (age 50–65) and “elder” group (age > 65), as displaced fractures (Garden Type III/IV) were in “younger” group. 233 hip fractures (68 males; 165 females) with a mean age of 73.04 ± 12.89 were included in the study. Surgical outcomes showed that the complication rate of hip screw fixation for all patients was 21.5% (50 patients) at 1 year. ACCI was significantly higher in all patients with complications (p = 0.000). Analysis within “younger” (p = 0.000) and “elder” groups (p = 0.006) both showed significance. Stepwise logistic regression modelling showed ACCI had positive correlation with complications with ACCI = 6 (OR 4.27, p = 0.02). R2 values were comparatively better after controlled by Garden Type III/IV at ACCI = 4 (OR 6.42 (1.70, 24.25), p = 0.01). The authors recommend that for patients with a Garden Type I/II and ACCI ≥ 6 or a Garden Type III/IV and ACCI ≥ 4, a direct arthroplasty surgery should be considered.

BackgroundElderly people with low lean and high fat mass, are diagnosed with sarcopenic obesity (SO), and often have poor clinical outcomes. This study aimed to explore the relationship between obesity and sarcopenia, and the optimal proportion of fat and muscle for old individuals.MethodsParticipants aged 60 years or above were instructed to perform bioelectrical impedance analysis to obtain the muscle and fat indicators, and handgrip strength was also performed. Sarcopenia was diagnosed according to predicted appendicular skeletal muscle mass and function. Body mass index (BMI) and body fat percentage (BF%) were used to define obesity. The association of muscle and fat indicators were analyzed by Pearson’s correlation coefficient. Pearson Chi-Square test was utilized to estimate odds ratios (OR) and 95% confidence intervals (CI) on the risk of sarcopenia according to obesity status.Results1637 old subjects (74.8 ± 7.8 years) participated in this study. Not only fat mass, but also muscle indicators were positively correlated to BMI and body weight (p < 0.05). Absolute muscle and fat mass in different positions had positive associations (p < 0.05). Muscle mass and strength were negatively related to appendicular fat mass percentage (p < 0.05). When defined by BMI (OR = 0.69, 95% CI [0.56, 0.86]; p = 0.001), obesity was a protective factor for sarcopenia, whilst it was a risk factor when using BF% (OR = 1.38, 95% CI [1.13, 1.69]; p = 0.002) as the definition. The risk of sarcopenia reduced with the increase of BMI in both genders. It was increased with raised BF% in males but displayed a U-shaped curve for females. BF% 26.0–34.6% in old females and lower than 23.9% in old males are recommended for sarcopenia and obesity prevention.ConclusionSkeletal muscle mass had strong positive relationship with absolute fat mass but negative associations with the percentage of appendicular fat mass. Obesity was a risk factor of sarcopenia when defined by BF% instead of BMI. The management of BF% can accurately help elderly people prevent against both sarcopenia and obesity.

Aims With the ageing population, fragility fractures have become one of the most common conditions. The objective of this study was to investigate whether microbiological outcomes and fracture-healing in osteoporotic bone is worse than normal bone with fracture-related infection (FRI). Methods A total of 120 six-month-old Sprague-Dawley (SD) rats were randomized to six groups: Sham, sham + infection (Sham-Inf), sham with infection + antibiotics (Sham-Inf-A), ovariectomized (OVX), OVX + infection (OVX-Inf), and OVX + infection + antibiotics (OVX-Inf-A). Open femoral diaphysis fractures with Kirschner wire fixation were performed. Staphylococcus aureus at 4 × 104 colony-forming units (CFU)/ml was inoculated. Rats were euthanized at four and eight weeks post-surgery. Radiography, micro-CT, haematoxylin-eosin, mechanical testing, immunohistochemistry (IHC), gram staining, agar plating, crystal violet staining, and scanning electron microscopy were performed. Results Agar plating analysis revealed a higher bacterial load in bone (p = 0.002), and gram staining showed higher cortical bone colonization (p = 0.039) in OVX-Inf compared to Sham-Inf. OVX-Inf showed significantly increased callus area (p = 0.013), but decreased high-density bone volume (p = 0.023) compared to Sham-Inf. IHC staining showed a significantly increased expression of TNF-α in OVX-Inf compared to OVX (p = 0.049). Significantly reduced bacterial load on bone (p = 0.001), enhanced ultimate load (p = 0.001), and energy to failure were observed in Sham-Inf-A compared to Sham-Inf (p = 0.028), but not in OVX-Inf-A compared to OVX-Inf. Conclusion In osteoporotic bone with FRI, infection was more severe with more bone lysis and higher bacterial load, and fracture-healing was further delayed. Systemic antibiotics significantly reduced bacterial load and enhanced callus quality and strength in normal bone with FRI, but not in osteoporotic bone. Cite this article: Bone Joint Res 2022;11(2):49–60.

Aims: The use of 3D printing has become increasingly popular and has been widely used in orthopaedic surgery. There has been a trend towards an increasing number of publications in this field, but existing literature incorporates limited high-quality studies, and there is a lack of reports on outcomes. The aim of this study was to perform a scoping review with Level I evidence on the application and effectiveness of 3D printing. Methods: A literature search was performed in PubMed, Embase, and Web of Science databases. The keywords used for the search criteria were ((3d print*) OR (rapid prototyp*) OR (additive manufactur*)) AND (orthopaedic). The inclusion criteria were: 1) use of 3D printing in orthopaedics, 2) randomized controlled trials, and 3) studies with participants/patients. Risk of bias was assessed with Cochrane Collaboration Tool and PEDro Score. Pooled analysis was performed. Results: Overall, 21 studies were included in our study with a pooled total of 932 participants. Pooled analysis showed that operating time (p < 0.001), blood loss (p < 0.001), fluoroscopy times (p < 0.001), bone union time (p < 0.001), pain (p = 0.040), accuracy (p < 0.001), and functional scores (p < 0.001) were significantly improved with 3D printing compared to the control group. There were no significant differences in complications. Conclusion: 3D printing is a rapidly developing field in orthopaedics. Our findings show that 3D printing is advantageous in terms of operating time, blood loss, fluoroscopy times, bone union time, pain, accuracy, and function. The use of 3D printing did not increase the risk of complications. Cite this article: Bone Joint Res 2021;10(12):807–819.

Abstract Background There are more than 300,000 hip fractures yearly in the USA with mortality rates of 20% within 1 year. The treatment of osteoporotic fractures is a major challenge as bone quality is poor, and healing is expected to delay due to the impaired healing properties with respect to bone formation, angiogenesis, and mineralization. Enhancement of osteoporotic fracture healing and function is therefore critical as a major goal in modern fracture management. Previous pre-clinical studies have shown that low-magnitude high-frequency vibration (LMHFV) accelerates osteoporotic fracture healing. The objective of this study is to investigate the effect of LMHFV on accelerating trochanteric hip fracture healing and functional recovery. Methods This is a randomized, double-blinded, placebo-controlled clinical trial to evaluate the effect of LMHFV in accelerating trochanteric hip fracture healing. All fractures undergo cephalomedullary nail fixation. The primary outcome of this study is time to fracture healing by X-ray. Computed tomography (CT) and dual-energy X-ray absorptiometry (DXA) will also be performed. Blood circulation at the fracture site will be assessed by dynamic perfusion magnetic resonance (MR). Clinical results include functional recovery by muscle strength, timed up and go test (TUG), quality of life questionnaire (SF-36), balancing, falls, and mortality. Discussion Previous animal studies have demonstrated LMHFV to improve both normal and osteoporotic fracture healing by accelerating callus formation and mineralization. The mechanical stimulation stimulates angiogenesis by significantly enhancing vascular volume and blood flow velocity. This is the first study to translate LMHFV to enhancing hip fracture healing clinically. Positive results would provide a huge impact in the recovery of hip fracture patients and save healthcare costs. Trial registration Clinicaltrials.gov NCT04063891. Registered on August 21, 2019

Abstract Background Gut microbiota dysbiosis and sarcopenia commonly occur in the elderly. Although the concept of the gut–muscle axis has been raised, the casual relationship is still unclear. This systematic review analyses the current evidence of gut microbiota effects on muscle/sarcopenia. Methods A systematic review was performed in PubMed, Embase, Web of Science, and The Cochrane Library databases using the keywords (microbiota* OR microbiome*) AND (sarcopen* OR muscle). Studies reporting the alterations of gut microbiota and muscle/physical performance were analysed. Results A total of 26 pre‐clinical and 10 clinical studies were included. For animal studies, three revealed age‐related changes and relationships between gut microbiota and muscle. Three studies focused on muscle characteristics of germ‐free mice. Seventy‐five per cent of eight faecal microbiota transplantation studies showed that the recipient mice successfully replicated the muscle phenotype of donors. There were positive effects on muscle from seven probiotics, two prebiotics, and short‐chain fatty acids (SCFAs). Ten studies investigated on other dietary supplements, antibiotics, exercise, and food withdrawal that affected both muscle and gut microbiota. Twelve studies explored the potential mechanisms of the gut–muscle axis. For clinical studies, 6 studies recruited 676 elderly people (72.8 ± 5.6 years, 57.8% female), while 4 studies focused on 244 young adults (29.7 ± 7.8 years, 55.4% female). The associations of gut microbiota and muscle had been shown in four observational studies. Probiotics, prebiotics, synbiotics, fermented milk, caloric restriction, and exercise in six studies displayed inconsistent effects on muscle mass, function, and gut microbiota. Conclusions Altering the gut microbiota through bacteria depletion, faecal transplantation, and various supplements was shown to directly affect muscle phenotypes. Probiotics, prebiotics, SCFAs, and bacterial products are potential novel therapies to enhance muscle mass and physical performance. Lactobacillus and Bifidobacterium strains restored age‐related muscle loss. Potential mechanisms of microbiome modulating muscle mainly include protein, energy, lipid, and glucose metabolism, inflammation level, neuromuscular junction, and mitochondrial function. The role of the gut microbiota in the development of muscle loss during aging is a crucial area that requires further studies for translation to patients.

ObjectivesThe aim of this study was to discover the role of fat and muscle in bone structures, as well as the relationship between obesity and sarcopenia on age-related osteoporosis.MethodsA total of 400 participants (65.0 ± 8.2 years old, 42.3% women) were recruited. Fat, muscle, bone parameters, basic demographics, medical history, physical performance and activity, and calcium intake of participants were obtained from datasets. The diagnosis of osteoporosis, sarcopenia, and obesity was based on current recommendations. Pearson correlation, non-linear regression models, and decision tree analyses were performed to study the relationship between fat, muscle, and bone. Logistic regression analyses were used to explore the risk of osteoporosis in old people with obesity or sarcopenia via Model 1 (unadjusted) and Model 2 (adjusted by age, physical activity, and calcium intake).ResultsCorrelation analysis showed that limb muscle mass and index, and age were best related to bone mineral density (BMD) (|r| = 0.386–0.632, p < 0.001). On the contrary, body mass index (BMI) and increased body fat percentage (BF%) were harmful for bone health. An increase of BMI and fat mass index slowed the increase of BMD in the spine, while skeletal muscle mass index accelerated the increase. People with sarcopenia had low muscle mass and strength. When separating subjects into sarcopenia and non-sarcopenia status, sarcopenia was independently related to higher risks of osteoporosis in both models (OR > 1, p < 0.05). BMI-defined obesity in Model 1 as well as BF%-defined obesity in both models did not reduce the risk of osteoporosis in both models (p > 0.05). The decision tree classification (85% accuracy) showed that greater body weight and larger lower limb muscle performance were negatively related to osteoporosis, while fat mass and percentage did not play roles in this prediction.ConclusionLow muscle mass and function were harmful to bone health. Obesity defined by both BMI and BF% had limited protective roles in osteoporosis. The benefits for bone from increased muscle mass and function play a more superior role than increased fat mass in old people. Sarcopenia prevention and treatment instead of controlling obesity should be recommended as an approach to reduce the risks of age-related osteoporosis and fragility fracture for elderly people.

Background: Osteocytes, composing over 90% of bone cells, are well known for their mechanosensing abilities. Aged osteocytes with impaired morphology and function are less efficient in mechanotransduction which will disrupt bone turnover leading to osteoporosis. The aim of this systematic review is to delineate the mechanotransduction mechanism at different stages in order to explore potential target for therapeutic drugs. Methods: A systematic literature search was performed in PubMed and Web of Science. Original animal, cell and clinical studies with available English full-text were included. Information was extracted from the included studies for review. Results: The 26 studies included in this review provided evidence that mechanical loading are sensed by osteocytes via various sensing proteins and transduced to different signaling molecules which later initiate various biochemical responses. Studies have shown that osteocyte plasma membrane and cytoskeletons are emerging key players in initiating mechanotransduction. Bone regulating genes expressions are altered in response to load sensed by osteocytes, but the genes involved different signaling pathways and the spatiotemporal expression pattern had made mechanotransduction mechanism complicated. Most of the included studies described the important role of osteocytes in pathways that regulate mechanosensing and bone remodeling. Conclusions: This systematic review provides an up-to-date insight to different steps of mechanotransduction. A better understanding of the mechanotransduction mechanism is beneficial in search of new potential treatment for osteoporotic patients. By delineating the unique morphology of osteocytes and their interconnected signaling network new targets can be discovered for drug development. Translational potential of this article: This systematic review provides an up-to-date sequential overview and highlights the different osteocyte-related pathways and signaling molecules during mechanotransduction. This allows a better understanding of mechanotransduction for future development of new therapeutic interventions to treat patients with impaired mechanosensitivity.

Abstract The objective of this study was to investigate the prognostic factors predicting the ambulation recovery of fragility hip fracture patients. 2286 fragility hip fracture patients were collected from the Fragility Fracture Registry in Hong Kong. Predictive factors of ambulation deterioration including age, gender, pre-operation American Society of Anesthesiologists grade, pre-fracture mobility, delay to surgery, length of stay, fracture type, type of surgery, discharge destination and complications were identified. Patients with outdoor unassisted and outdoor with aids ambulatory function before fracture had 3- and 1.5-times increased risk of mobility deterioration, respectively (Odds Ratio (OR) = 2.556 and 1.480, 95% Confidence Interval (CI) 2.101–3.111 and 1.246–1.757, both p 14 days), early discharge (less than 6 days), and length of stay also did not increased risk of mobility decline. Male patients performed worse in terms of their mobility function after surgery compared to female patients (OR = 1.195, 95% CI 1.070–1.335, p = 0.002). This study identified that better premorbid good function, discharge to old age homes especially newly institutionalized patients, increased age, lower ASA score, and male patients, correlate with mobility deterioration at 1-year post-surgery. With the aging population and development of FLS, prompt identification of at-risk patients should be performed for prevention of deterioration.

Abstract Background Vertebral compression fractures (VCFs) are the most common among all osteoporotic fractures. The body may compensate to the kyphosis from vertebral compression fractures with lordosis of the adjacent spinal segments, rotation of the pelvis, knee flexion and ankle dorsiflexion. However, the detailed degree of body compensation, especially the lower limb, remains uncertain. Herein, the aim of this study is to investigate the values of global sagittal alignments (GSA) parameters, including the spine, pelvis and lower limbs, in patients with and without VCFs, as well as to evaluate the effect of VCFs on various quality of life (QoL) parameters. Methods A cross-sectional study was conducted from May 2015 to June 2018. A total of 142 patients with VCFs aged over 60 years old and 108 age-matched asymptomatic controls were recruited. Whole body sagittal alignment including thoracic kyphosis (TK), lumbar lordosis (LL), pelvic tilt (PT), pelvic incidence (PI), sagittal vertical axis (SVA), T1-pelvic angle (TPA), knee-flex angle (KA) and ankle-flex angle (AA) were measured. In addition, lower back pain and quality of life were assessed using self-reported questionnaires. Results Compared to asymptomatic controls, patients with VCF showed significantly greater TK (33.4o ± 16.4o vs 28.4o ± 11.4o; p

Aims: The effect of the gut microbiota (GM) and its metabolite on bone health is termed the gut-bone axis. Multiple studies have elucidated the mechanisms but findings vary greatly. A systematic review was performed to analyze current animal models and explore the effect of GM on bone. Methods: Literature search was performed on PubMed and Embase databases. Information on the types and strains of animals, induction of osteoporosis, intervention strategies, determination of GM, assessment on bone mineral density (BMD) and bone quality, and key findings were extracted. Results: A total of 30 studies were included, of which six studies used rats and 24 studies used mice. Osteoporosis or bone loss was induced in 14 studies. Interventions included ten with probiotics, three with prebiotics, nine with antibiotics, two with short-chain fatty acid (SCFA), six with vitamins and proteins, two with traditional Chinese medicine (TCM), and one with neuropeptide Y1R antagonist. In general, probiotics, prebiotics, nutritional interventions, and TCM were found to reverse the GM dysbiosis and rescue bone loss. Conclusion: Despite the positive therapeutic effect of probiotics, prebiotics, and nutritional or pharmaceutical interventions on osteoporosis, there is still a critical knowledge gap regarding the role of GM in rescuing bone loss and its related pathways.

Aims: Fibrinolysis plays a key transition step from haematoma formation to angiogenesis and fracture healing. Low-magnitude high-frequency vibration (LMHFV) is a non-invasive biophysical modality proven to enhance fibrinolytic factors. This study investigates the effect of LMHFV on fibrinolysis in a clinically relevant animal model to accelerate osteoporotic fracture healing. Methods: A total of 144 rats were randomized to four groups: sham control; sham and LMHFV; ovariectomized (OVX); and ovariectomized and LMHFV (OVX-VT). Fibrinolytic potential was evaluated by quantifying fibrin, tissue plasminogen activator (tPA), and plasminogen activator inhibitor-1 (PAI-1) along with healing outcomes at three days, one week, two weeks, and six weeks post-fracture. Results: All rats achieved healing, and x-ray relative radiopacity for OVX-VT was significantly higher compared to OVX at week 2. Martius Scarlet Blue (MSB) staining revealed a significant decrease of fibrin content in the callus in OVX-VT compared with OVX on day 3 (p = 0.020). Mean tPA from muscle was significantly higher for OVX-VT compared to OVX (p = 0.020) on day 3. Mechanical testing revealed the mean energy to failure was significantly higher for OVX-VT at 37.6 N mm (SD 8.4) and 71.9 N mm (SD 30.7) compared with OVX at 5.76 N mm (SD 7.1) (p = 0.010) and 17.7 N mm (SD 11.5) (p = 0.030) at week 2 and week 6, respectively. Conclusion: Metaphyseal fracture healing is enhanced by LMHFV, and one of the important molecular pathways it acts on is fibrinolysis. LMHFV is a promising intervention for osteoporotic metaphyseal fracture healing. The improved mechanical properties, acceleration of fracture healing, and safety justify its role into translation to future clinical studies.

Abstract Background Sarcopenia is an aging‐induced deterioration of skeletal muscle mass and function. Low‐magnitude high‐frequency vibration (LMHFV) was shown to improve muscle functions and β‐hydroxy‐β‐methylbutyrate (HMB) to increase muscle mass and strength. Muscle‐derived stem cells (MDSCs) are progenitor cells important for muscle regeneration. We hypothesized that LMHFV and HMB could retard sarcopenia by reducing fat infiltration through inhibiting adipogenesis in MDSCs. Methods Senescence‐accelerated mouse P8 male mice were randomized into control (CTL), HMB, LMHFV (VIB), and combined (COM) groups. Interventions started at age of month 7 and assessed at 1, 2, and 3 months post‐intervention by densitometry, histology, and functional tests. In vitro, MDSCs isolated from gastrocnemius of senescence‐accelerated mouse P8 mice were characterized, randomized into CTL, VIB, HMB, and COM groups, and assessed by oil red O staining, mRNA, and protein expression. Results At 2 months post‐intervention, percentage lean mass of HMB, VIB, and COM groups were significantly higher than CTL group. Twitch, tetanic, and specific tetanic forces of COM group were higher, while specific twitch force of both VIB and COM groups were higher. Grip strength of HMB, VIB, and COM groups were higher. Histologically, both VIB and COM groups presented lower oil red O area than CTL group. Type I muscle fibre in CTL group was higher than HMB, VIB, and COM groups. MDSC were detected in situ by immunofluorescence stain with stem cell antigen‐1 signals confirmed with higher β‐catenin expression in the COM group. The observations were also confirmed in vitro, MDSCs in the HMB, VIB, and COM groups presented lower adipogenesis vs. the CTL group. β‐Catenin mRNA and protein expressions were lower in the CTL group while their relationship was further validated through β‐catenin knock‐down approach. Conclusions Our results showed that combined LMHFV and HMB interventions enhanced muscle strength and decreased percentage fat mass and intramuscular fat infiltration as compared with either treatment alone. Additive effect of LMHFV and HMB was demonstrated in β‐catenin expression than either treatment in MDSCs and altered cell fate from adipogenesis to myogenesis, leading to inhibition of intramuscular lipid accumulation. Wnt/β‐catenin signalling pathway was found to be the predominant regulatory mechanism through which LMHFV and HMB combined treatment suppressed MDSCs adipogenesis.

Background: Although emerging studies have provided evidence that osteocytes are actively involved in fracture healing, there is a general lack of a detailed understanding of the mechanistic pathway, cellular events and expression of markers at different phases of healing. Methods: This systematic review describes the role of osteocytes in fracture healing from early to late phase. Literature search was performed in PubMed and Embase. Original animal and clinical studies with available English full-text were included. Information was retrieved from the selected studies. Results: A total of 23 articles were selected in this systematic review. Most of the studies investigated changes of various genes and proteins expression patterns related to osteocytes. Several studies have described a constant expression of osteocyte-specific marker genes throughout the fracture healing cascade followed by decline phase with the progress of healing, denoting the important physiological role of the osteocyte and the osteocyte lacuno-canalicular network in fracture healing. The reports of various markers suggested that osteocytes could trigger coordinated bone healing responses from cell death and expression of proinflammatory markers cyclooxygenase-2 and interleukin 6 at early phase of fracture healing. This is followed by the expression of growth factors bone morphogenetic protein-2 and cysteine-rich angiogenic inducer 61 that matched with the neo-angiogenesis, chondrogenesis and callus formation during the intermediate phase. Tightly controlled regulation of osteocyte-specific markers E11/Podoplanin (E11), dentin matrix protein 1 and sclerostin modulate and promote osteogenesis, mineralisation and remodelling across different phases of fracture healing. Stabilised fixation was associated with the finding of higher number of osteocytes with little detectable bone morphogenetic proteins expressions in osteocytes. Sclerostin-antibody treatment was found to result in improvement in bone mass, bone strength and mineralisation. Conclusion: To further illustrate the function of osteocytes, additional longitudinal studies with appropriate clinically relevant model to study osteoporotic fractures are crucial. Future investigations on the morphological changes of osteocyte lacuno-canalicular network during healing, osteocyte-mediated signalling molecules in the transforming growth factor-beta-Smad3 pathway, perilacunar remodelling, type of fixation and putative biomarkers to monitor fracture healing are highly desirable to bridge the current gaps of knowledge.The translational potential of this article: This systematic review provides an up-to-date chronological overview and highlights the osteocyte-regulated events at gene, protein, cellular and tissue levels throughout the fracture healing cascade, with the hope of informing and developing potential new therapeutic strategies that could improve the timing and quality of fracture healing in the future. Keywords: Dentin matrix protein 1, Fracture healing, Lacuno-canalicular network, Osteocyte, Sclerostin, TGF-Beta-Smad3

Introduction: Knee osteoarthritis is a leading cause of disability and medical costs. The effect of whole-body vibration in knee osteoarthritis is controversial. The aim of this study was to assess the effects and safety of whole-body vibration on pain, stiffness, physical function, and muscle strength in patients with knee osteoarthritis. Methods: PubMed, Scopus, Web of Science, Physiotherapy Evidence Database (PEDro) and EMBASE databases were searched (date last accessed 1 April 2021) using the key words “vibration” and “knee osteoarthritis”, to identify all randomized controlled trials related to whole-body vibration and knee osteoarthritis. Outcomes related to pain, stiffness, physical function, muscle strength, adverse events were included. The risk of bias and quality were assessed by the Cochrane Collaboration tool and PEDro scale. A systematic review and meta-analysis were performed. Subgroup analysis was performed for low- and high-frequency interventions. Results: A total of 14 randomized controlled trials involving 559 patients with knee osteoarthritis met the inclusion criteria. Nine studies were good-quality trials (PEDro score=6–8), and 5 studies were fairquality trials (PEDro score=4–5). Ten studies were included in the meta-analysis. One study showed negative effects of whole-body vibration on knee osteoarthritis. The duration of whole-body vibration ranged from 4 to 24 weeks. Meta-analysis revealed that whole-body vibration with strengthening exercises has a significant treatment effect on pain score (standardized mean difference (SMD) = 0.46 points, 95% confidence interval (95% CI) = 0.20–0.71, p = 0.0004), the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC-function) (SMD = 0.51 points, 95% CI = 0.27–0.75, p < 0.0001), Timed Up and Go (TUG) test (SMD = 0.82 points, 95% CI = 0.46–1.18, p < 0.00001), extensor isokinetic peak torque (SMD = 0.65 points, 95% CI = 0.00–1.29, p = 0.05), peak power (SMD = 0.68 points, 95% CI = 0.26–1.10, p = 0.001), and extensor isometric strength (SMD = 0.44 points, 95% CI = 0.13–0.75, p = 0.006). Both low-frequency (10–30 Hz) and highfrequency (30–40 Hz) whole-body vibration were associated with significant changes in pain, physical function, and knee extensor strength (p < 0.05). WBV was not associated with significant changes in stiffness, balance ability, quality of life, and knee flexor strength. No adverse events were reported. Conclusion: Meta-analysis showed that low-frequency and high-frequency whole-body vibration had additional positive effects compared with strengthening exercises alone on pain, knee extensor muscle strength, and physical function in individuals with knee OA. Whole-body vibration with strengthening exercises can be incorporated into treatment protocols. LAY ABSTRACT Knee osteoarthritis is a leading cause of disability and medical costs. Osteoarthritis leads to pain, stiffness, swelling and loss of function, resulting in poor quality of life. Whole-body vibration is a non-invasive treatment that has been proposed to improve muscle strength and physical performance. This analysis of 14 randomized controlled trials showed that, compared with exercise alone, wholebody vibration with exercise had positive effects on pain, physical function, and knee extensor muscle strength in patients with knee osteoarthritis. Based on these findings, we recommend whole-body vibration used together with strengthening exercises for knee osteoarthritis.

Cement arterio-venogram is a rare event with cement extrusion into femoral nutrient vessels. In literature it is known to be benign with no significant clinical sequelae. It is postulated that it is due to high cement implantation pressure, that results in optimal cement filling quality. All previously reported cases were female patients, and it is thought to be a female only phenomenon due to the relatively narrow femoral canal leading to higher pressures during cementation. In this case series we report 3 cases different to existing literature. All 3 patients showed a cement arterio-venogram together with bone cement implantation syndrome and hypotension intraoperatively. It was also observed that during implantation the cement was of low viscosity. We postulate low cement viscosity during implantation with pressurization is also a contributing factor to these phenomena. This case series also demonstrates the first 2 male cases, showing this the even can occur in males too. The cement arteriovenogram is located at 41%–42% femur length which is within the ‘third sixth’ of the length of the femur. Good cementation techniques and prevention is also highlighted in this report.

Abstract Background Fractures of the distal radius are one of the most common osteoporotic fractures in elderly men and women. These fractures are a particular health concern amongst the elderly, who are at risk of fragility fractures, and are associated with long-term functional impairment, pain and a variety of complications. This is a sentinel event, as these fractures are associated with a two to four times increased risk of subsequent hip fractures in elderly patients. This is an important concept, as it is well established that these patients have an increased risk of falling. Fall prevention is therefore crucial to decrease further morbidity and mortality. The purpose of this study is to investigate the effect of low-magnitude high-frequency vibration (LMHFV) on postural stability and prevention of falls in elderly patients post distal radius fracture. Methods This is a prospective single-blinded randomized controlled trial. Two hundred patients will be recruited consecutively with consent, and randomized to either LMHFV (n = 100) or a control group (n = 100). The primary outcome is postural stability measured by the static and dynamic ability of patients to maintain centre of balance on the Biodex Balance System SD. Secondary outcomes are the occurrence of fall(s), the health-related quality of life 36-item short form instrument, the Timed Up and Go test for basic mobility skills, compliance and adverse events. Outcome assessments for both groups will be performed at baseline (0 month) and at 6 weeks, 3 months and 6 months time points. Discussion Previous studies have stressed the importance of reducing falls after distal radius fracture has occurred in elderly patients, and an effective intervention is crucial. Numerous studies have proven vibration therapy to be effective in improving balancing ability in normal patients; However, no previous study has applied the device for patients with fractures. Our study will attempt to translate LMHFV to patients with fractures to improve postural stability and prevent recurrent falls. Positive results would provide a large impact on the prevention of secondary fractures and save healthcare costs. Trial registration ClinicalTrials.gov, NCT03380884. Registered on 21 December 2017.

Sarcopenia is an aging process with a decline of skeletal muscle mass and function, which is a challenging public health problem with reduced quality of life in patients. The endplate, the post-synaptic part of the neuromuscular junction (NMJ), occupies 0.1% of the myofiber surface area only, but is composed of millions of acetylcholine receptors (AChRs) that are efficient in binding to acetylcholine (ACh) and triggering skeletal muscle contraction. This systematic review aims to examine aging-associated alterations of post-synaptic AChRs, including morphology, function and related gene expression. A systematic literature search was conducted in PubMed, Embase and Web of Science with relevant keywords by two independent reviewers. Original pre-clinical and clinical studies regarding AChRs changes during aging with available full text and written in English were included. Information was extracted from the included studies for further review. In total, 30 articles were included. Various parameters assessing AChRs alterations by radioassay, immunofluorescence, electrophysiology and mechanical test were reported. Endplate fragmentation and denervation were common in old skeletal muscles during aging. To ensure efficient NMJ transmission and force generation, type I or IIb muscle fibers tended to have increased ACh quanta releasing after electrical stimulations, while type IIa muscle fibers tended to have stronger binding between ACh and AChRs, but the overall function of AChRs was reduced during aging. Alterations of AChRs area depended on muscle type, species and the progress of muscle atrophy and type I muscles fibers tended to demonstrate enlarging AChRs areas. Myogenic regulator factors (MRFs) can regulate the expression of AChRs subunits, while decreased MRF4 may lead to expression changes of AChRs subunits during aging. Sarcoglycan-α can delay low-density lipoprotein receptor-related protein 4 (LRP4) degradation. This protein was increased in old muscles but still cannot suppress the degradation of LRP4. Investigating the role of these AChRs-related genes in the process of aging may provide a potential target to treat sarcopenia.