Sarcopenia and Ageing.

Musculoskeletal ageing is a major health challenge as muscles and bones constitute around 55-60% of body weight. Ageing muscles will result in sarcopenia that is characterized by progressive and generalized loss of skeletal muscle mass and strength with a risk of adverse outcomes. In recent years, a few consensus panels provide new definitions for sarcopenia. It was officially recognized as a disease in 2016 with an ICD-10-CM disease code, M62.84, in the International Classification of Diseases (ICD). With the new definitions, there are many studies emerging to investigate the pathogenesis of sarcopenia, exploring new interventions to treat sarcopenia and evaluating the efficacy of combination treatments for sarcopenia. The scope of this chapter is to summarize and appraise the evidence in terms of (1) clinical signs, symptoms, screening, and diagnosis, (2) pathogenesis of sarcopenia with emphasis on mitochondrial dysfunction, intramuscular fat infiltration and neuromuscular junction deterioration, and (3) current treatments with regard to physical exercises and nutritional supplement.

The imminent risk of a fracture-existing worldwide data: a systematic review and meta-analysis.

The overall incidence of imminent fracture after a prior fragility fracture was 7.58% in the first year and 11.58% in the first 2 years. Approximately half of re-fractures occurred in the first 2 years after a fragility fracture. Older patients that have suffered from a fragility fracture should be treated promptly, with immediate care and a secondary fracture prevention to prevent the high imminent risk of a fracture. INTRODUCTION: Imminent fractures refer to the fractures that occur within 2 years of an initial fracture. It is well known that the risk of a subsequent fracture is not constant with time and occurs shortly after the initial one. This systematic review and meta-analysis aimed to present the existing data on imminent fracture worldwide. METHODS: Literature search was conducted in Pubmed, Embase, and Web of Science databases until 26 October 2021 for studies reporting the incidence of imminent osteoporotic fractures among people aged 50 years or older. The overall incidence of imminent fracture was pooled and subgroup analyses of index fracture sites and regions on incidence of imminent fracture were performed, with the 95% confidence interval (CI) being calculated. Percentage of imminent fracture occurring in follow-up period was calculated and pooled by meta-analysis. Hazard ratio (HR) was used to estimate the gender differences on the imminent risk of fracture. RESULTS: A total of 1446 articles were identified. Nineteen observational studies were eligible for our systematic review, in which 18 were used for quantitative analysis. Pooled overall incidence of imminent fracture in the first year after an osteoporotic fracture was 7.58% (95% CI 5.84 to 9.31%) and cumulative incidence in the first 2 years was 11.58% (95% CI 8.94 to 14.21%). Subgroup analysis showed that in the first 2 years, the pooled incidence in Asia was 7.30% (95% CI 3.42 to 11.18%), whilst incidence in Europe/North America was 13.17% (95% CI 10.14 to 16.20%). In included studies with follow-up period of more than 5 years, pooled imminent fracture percentage in the first 2 years was 47.24% (95% CI 26.18 to 68.30%). Hazard ratio (HR) on gender showed that women had an overall slight increase in risk of imminent fractures (HR 1.18, 95% CI 1.11 to 1.25). CONCLUSION: The incidence of imminent fracture is high globally at 11.58%. Approximately half of all refractures occur in the first 2 years after an index fragility fracture. Older patients that have suffered from a fragility fracture should be treated promptly. Also, immediate care and secondary fracture prevention are necessary to prevent the high imminent risk of a fracture, especially within the first 2 years.

Coapplication of Magnesium Supplementation and Vibration Modulate Macrophage Polarization to Attenuate Sarcopenic Muscle Atrophy through PI3K/Akt/mTOR Signaling Pathway.

Sarcopenia is an age-related geriatric syndrome characterized by the gradual loss of muscle mass and function. Low-magnitude high-frequency vibration (LMHFV) was shown to be beneficial to structural and functional outcomes of skeletal muscles, while magnesium (Mg) is a cofactor associated with better indices of skeletal muscle mass and strength. We hypothesized that LMHFV, Mg and their combinations could suppress inflammation and sarcopenic atrophy, promote myogenesis via PI3k/Akt/mTOR pathway in senescence-accelerated mouse P8 (SAMP8) mice and C2C12 myoblasts. Results showed that Mg treatment and LMHFV could significantly decrease inflammatory expression (C/EBPα and LYVE1) and modulate a CD206-positive M2 macrophage population at month four. Mg treatment also showed significant inhibitory effects on FOXO3, MuRF1 and MAFbx mRNA expression. Coapplication showed a synergistic effect on suppression of type I fiber atrophy, with significantly higher IGF-1, MyoD, MyoG mRNA (p < 0.05) and pAkt protein expression (p < 0.0001) during sarcopenia. In vitro inhibition of PI3K/Akt and mTOR abolished the enhancement effects on myotube formation and inhibited MRF mRNA and p85, Akt, pAkt and mTOR protein expressions. The present study demonstrated that the PI3K/Akt/mTOR pathway is the predominant regulatory mechanism through which LMHFV and Mg enhanced muscle regeneration and suppressed atrogene upregulation.

Can we enhance osteoporotic metaphyseal fracture healing through enhancing ultrastructural and functional changes of osteocytes in cortical bone with low-magnitude high-frequency vibration?

Fragility fractures are related to the loss of bone integrity and deteriorated morphology of osteocytes. Our previous studies have reported that low-magnitude high-frequency vibration (LMHFV) promoted osteoporotic fracture healing. As osteocytes are known for mechanosensing and initiating bone repair, we hypothesized that LMHFV could enhance osteoporotic fracture healing through enhancing morphological changes in the osteocyte lacuna-canalicular network (LCN) and mineralization. A metaphyseal fracture model was established in female Sprague-Dawley rats to investigate changes in osteocytes and healing outcomes from early to late phase post-fracture. Our results showed that the LCN exhibited an exuberant outgrowth of canaliculi in the osteoporotic fractured bone at day 14 after LMHFV. LMHFV upregulated the E11, dentin matrix protein 1 (DMP1), and fibroblast growth factor 23 (FGF23), but downregulated sclerostin (Sost) in osteocytes. Moreover, LMHFV promoted mineralization with significant enhancements of Ca/P ratio, mineral apposition rate (MAR), mineralizing surface (MS/BS), and bone mineral density (BMD) in the osteoporotic group. Consistently, better healing was confirmed by microarchitecture and mechanical properties, whereas the enhancement in osteoporotic group was comparable or even greater than the normal group. This is the first report to reveal the enhancement effect of LMHFV on the osteocytes' morphology and functions in osteoporotic fracture healing.

Acute Inflammatory Response in Osteoporotic Fracture Healing Augmented with Mechanical Stimulation is Regulated In Vivo through the p38-MAPK Pathway.

Low-magnitude high-frequency vibration (LMHFV) has previously been reported to modulate the acute inflammatory response of ovariectomy-induced osteoporotic fracture healing. However, the underlying mechanisms are not clear. In the present study, we investigated the effect of LMHFV on the inflammatory response and the role of the p38 MAPK mechanical signaling pathway in macrophages during the healing process. A closed femoral fracture SD rat model was used. In vivo results showed that LMHFV enhanced activation of the p38 MAPK pathway at the fracture site. The acute inflammatory response, expression of inflammatory cytokines, and callus formation were suppressed in vivo by p38 MAPK inhibition. However, LMHFV did not show direct in vitro enhancement effects on the polarization of RAW264.7 macrophage from the M1 to M2 phenotype, but instead promoted macrophage enlargement and transformation to dendritic monocytes. The present study demonstrated that p38 MAPK modulated the enhancement effects of mechanical stimulation in vivo only. LMHFV may not have exerted its enhancement effects directly on macrophage, but the exact mechanism may have taken a different pathway that requires further investigation in the various subsets of immune cells.

The Predictive Value of Sarcopenia and Falls for 2-Year Major Osteoporotic Fractures in Community-Dwelling Older Adults.

To evaluate the associations of sarcopenia and previous falls with 2-year major osteoporotic fractures (MOFs) in community-dwelling older adults. Four thousand Chinese men and women ≥ 65 years recruited from Hong Kong communities were prospectively followed up. Measures of muscle mass, grip strength, gait speed and falls in the previous year were recorded at baseline, the 2nd year and the 4th year visit for each subject. The associations of fall history, sarcopenia and its components with 2-year MOFs were evaluated using generalized linear mixed models. Poor grip strength and poor gait speed were significantly associated with a higher 2-year MOFs risk, with an adjusted OR (95% CI) per one SD decrease of 1.48 (1.17, 1.87) and 1.17 (1.00, 1.36), respectively. Falls in the previous year was a significant predictor for 2-year MOFs risk, with an adjusted OR (95% CI) per one added fall of 1.85 (1.40, 2.44) in men and 1.26 (1.01, 1.58) in women. The adjusted OR (95% CI) of height adjusted appendicular lean muscle mass (ALM/height2) per one SD decrease and sarcopenia for 2-year MOFs risk were 1.34 (0.87, 2.06) and 1.72 (0.92, 3.21) in men, and were 0.73 (0.57, 0.93) and 0.76 (0.39, 1.47) in women, respectively (P for interaction by gender = 0.012 and 0.017, respectively). Poor sarcopenia-related physical performance and falls in the previous year were significant predictors for 2-year MOFs in community-dwelling older adults. The predictive value of ALM by DXA for near-term fracture risk is limited and different across genders.

Coadministrating luteolin minimizes the side effects of the aromatase inhibitor letrozole.

Aromatase inhibitors (AIs) have been used as adjuvant therapeutic agents for breast cancer. Their adverse side effect on blood lipid is well documented. Some natural compounds have been shown to be potential AIs. In the present study, we compared the efficacy of the flavonoid luteolin to the clinically approved AI letrozole (Femara; Novartis Pharmaceuticals, East Hanover, NJ) in a cell and a mouse model. In the in vitro experimental results for aromatase inhibition, the Ki values of luteolin and letrozole were estimated to be 2.44 µM and 0.41 nM, respectively. Both letrozole and luteolin appeared to be competitive inhibitors. Subsequently, an animal model was used for the comparison. Aromatase-expressing MCF-7 cells were transplanted into ovariectomized athymic mice. Luteolin was given by mouth at 5, 20, and 50 mg/kg, whereas letrozole was administered by intravenous injection. Similar to letrozole, luteolin administration reduced plasma estrogen concentrations and suppressed the xenograft proliferation. The regulation of cell cycle and apoptotic proteins-such as a decrease in the expression of Bcl-xL, cyclin-A/D1/E, CDK2/4, and increase in that of Bax-was about the same in both treatments. The most significant disparity was on blood lipids. In contrast to letrozole, luteolin increased fasting plasma high-density lipoprotein concentrations and produced a desirable blood lipid profile. These results suggested that the flavonoid could be a coadjuvant therapeutic agent without impairing the action of AIs.

Callus formation is related to the expression ratios of estrogen receptors-alpha and -beta in ovariectomy-induced osteoporotic fracture healing.

INTRODUCTION: This study characterizes ovariectomized (OVX)-induced osteoporotic fracture healing with focus on estrogen receptors (ERs). Callus formation plays a critical role in fracture healing, and ERs are well-known mechanosensors in osteogenic pathways. It was hypothesized that callus formation was related to and partially determined by the difference in expression patterns of ERs in both normal and OVX-induced osteoporotic fractures. METHODS: Closed femoral fracture in SHAM and ovariectomized rats were used in this study. Weekly callus width (CW) and area (CA), endpoint mechanical properties, gene expressions of Col-1, BMP-2, ER-α, ER-ß and ER-α:ER-ß ratios (ER-ratios), and correlations were assessed at 2, 4 and 8 weeks post-fracture. RESULTS: CW and CA results confirmed that OVX-induced osteoporotic fracture was delayed at 2-4 weeks with impaired endpoint mechanical properties. Gene expressions of ER-α and ER-ß were higher in the SHAM group at week 2 (p < 0.05) and later lowered at week 8; whereas the OVX group showed an opposing trend. Moderate correlation existed between ER-α and BMP-2 (0.545, p = 0.003), and ER-ratio and BMP-2 (0.601, p = 0.001), and BMP-2 to CW and CA (r = 0.709, p = 0.000 and r = 0.588, p = 0.001, respectively). ER-α and ER-ß proteins expressions were confirmed by immunohistochemistry at the fracture callus in reparative progenitor cells, osteoblasts- and osteoclasts-like cells. CONCLUSION: We conclude that the delayed healing rate and impaired callus quality in OVX-induced osteoporotic fracture is related to the delayed expression of ERs. A high ER-α:ER-ß ratio favors callus formation.

Effects of physical exercise on neuromuscular junction degeneration during ageing: A systematic review.

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.

Prevention of age-related neuromuscular junction degeneration in sarcopenia by low-magnitude high-frequency vibration.

Neuromuscular junction (NMJ) degeneration is one of pathological factors of sarcopenia. Low-magnitude high-frequency vibration (LMHFV) was reported effective in alleviating the sarcopenia progress. However, no previous study has investigated treatment effects of LMHFV targeting NMJ degeneration in sarcopenia. We first compared morphological differences of NMJ between sarcopenic and non-sarcopenic subjects, as well as young and old C57BL/6 mice. We then systematically characterized the age-related degeneration of NMJ in SAMP8 against its control strain, SAMR1 mice, from 3 to 12 months old. We also investigated effects of LMHFV in SAMP8 on the maintenance of NMJ during the onset of sarcopenia with respect to the Agrin-LRP4-MuSK-Dok7 pathway and investigated the mechanism related to ERK1/2 signaling. We observed sarcopenic/old NMJ presented increased acetylcholine receptors (AChRs) cluster fragmentation and discontinuity than non-sarcopenic/young NMJ. In SAMP8, NMJ degeneration (morphologically at 6 months and functionally at 8 months) was observed associated with the sarcopenia onset (10 months). SAMR1 showed improved NMJ morphology and function compared with SAMP8 at 10 months. Skeletal muscle performance was improved at Month 4 post-LMHFV treatment. Vibration group presented improved NMJ function at Months 2 and 6 posttreatment, accompanied with alleviated morphological degeneration at Month 4 posttreatment. LMHFV increased Dok7 expression at Month 4 posttreatment. In vitro, LMHFV could promote AChRs clustering in myotubes by increasing Dok7 expression through suppressing ERK1/2 phosphorylation. In conclusion, NMJ degeneration was observed associated with the sarcopenia onset in SAMP8. LMHFV may attenuate NMJ degeneration and sarcopenia progression by increasing Dok7 expression through suppressing ERK1/2 phosphorylation.

Implants coating strategies for antibacterial treatment in fracture and defect models: A systematic review of animal studies.

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.

Biophysical and nutritional combination treatment for myosteatosis in patients with sarcopenia: a study protocol for single-blinded randomised controlled trial.

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 ß-hydroxy ß-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.

Potential of Fatty Acids in Treating Sarcopenia: A Systematic Review.

This paper presents a systematic review of studies investigating the effects of fatty acid supplementation in potentially preventing and treating sarcopenia. PubMed, Embase, and Web of Science databases were searched using the keywords 'fatty acid' and 'sarcopenia'. Results: A total of 14 clinical and 11 pre-clinical (including cell and animal studies) studies were included. Of the 14 clinical studies, 12 used omega-3 polyunsaturated fatty acids (PUFAs) as supplements, 1 study used ALA and 1 study used CLA. Seven studies combined the use of fatty acid with resistant exercises. Fatty acids were found to have a positive effect in eight studies and they had no significant outcome in six studies. The seven studies that incorporated exercise found that fatty acids had a better impact on elderlies. Four animal studies used novel fatty acids including eicosapentaenoic acid, trans-fatty acid, and olive leaf extraction as interventions. Three animal and four cell experiment studies revealed the possible mechanisms of how fatty acids affect muscles by improving regenerative capacity, reducing oxidative stress, mitochondrial and peroxisomal dysfunctions, and attenuating cell death. Conclusion: Fatty acids have proven their value in improving sarcopenia in pre-clinical experiments. However, current clinical studies show controversial results for its role on muscle, and thus the mechanisms need to be studied further. In the future, more well-designed randomized controlled trials are required to assess the effectiveness of using fatty acids in humans.

Does the regulation of skeletal muscle influence cognitive function? A scoping review of pre-clinical evidence.

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.

Does exercise influence skeletal muscle by modulating mitochondrial functions via regulating MicroRNAs? A systematic review.

BACKGROUND: Sarcopenia is the accelerated loss of muscle mass, strength and function. Mitochondrial dysfunction was related to the progression of sarcopenia; meanwhile, microRNAs were regarded as core roles in regulating mitochondrial function. Physical exercise is a well-accepted approach to attenuate sarcopenia, yet very few studies depict the molecular mechanisms. The aim of this systematic review is to explore the potential relationships among physical exercise, mitochondrial function, and microRNAs, which may give new insight for retarding sarcopenia. METHODS: A systematic literature search was performed in PubMed, Embase and Web of Science. The keywords were combined as "(microRNA OR miR) AND mitochondri* AND muscle AND exercise" and searched in all fields. PRISMA guidelines were followed. Information was extracted from the included studies for review. RESULTS: In this review, 18 preclinical studies and 5 clinical studies were included. Most of the included studies suggested that effective physical exercise had positive effects on mitochondrial functions by regulating microRNAs. The results showed that 12 microRNAs improved mitochondrial functions, while 18 microRNAs suppressed them. Meanwhile, the results showed that 5 microRNAs improved muscle performance. CONCLUSIONS: This systematic review provides an up-to-date sequential overview and highlights the potential relationship among exercise, mitochondrial function, and microRNAs in muscle. Meanwhile, evidence revealed that physical exercise can improve muscle performance by up-regulating mitochondrial functions, especially mitochondrial biogenesis, through modulating microRNAs.

Study on the Optimal Surgical Scheme for Very Severe Osteoporotic Vertebral Compression Fractures.

OBJECTIVE: Therapy of very severe osteoporotic compression fractures (VSOVCF) has been a growing challenge for spine surgeons. Opinions vary regarding the optimal surgical procedure for the treatment of VSOVCF and which internal fixation method is more effective is still under debate, and research on this topic is lacking. This retrospective study was conducted to compare the efficacy and safety of various pedicle screw fixation methods for treating VSOVCF. METHODS: This single-center retrospective comparative study was conducted between January 2015 and September 2020. Two hundred and one patients were divided into six groups according to different surgical methods: 45 patients underwent long-segment fixation (Group 1); 39 underwent short-segment fixation (Group 2); 30 received long-segment fixation with cement-reinforced screws (Group 3); 32 received short-segment fixation with cement-reinforced screws (Group 4); 29 had long-segment fixation combined with kyphoplasty (PKP) (Group 5); and 26 cases had short-segment fixation combined with PKP (Group 6). The clinical records were reviewed and the visual analogue scale (VAS) score and the Oswestry Disability Index (ODI) score were used for clinical evaluation. The vertebral height (VH), fractured vertebral body height (FVBH), and Cobb's angle were objectively calculated and analyzed on lateral plain radiographs. Student's t-tests and one-way ANOVA among groups were conducted to analyze the continuous, and the chi-squared test was used to compare the dichotomous or categorical variables. The difference was considered statistically significant when the P-value was less than 0.05. RESULTS: The six groups had similar distributions in age, gender, course of the disease, follow-up period, and injured level. In the postoperative assessment of the VAS score, the surgical intervention most likely to rank first in terms of pain relief was the short-segment fixation with cement-reinforced screws (Group 4). For the functional evaluation, the surgical intervention that is most likely to rank first in terms of ODI score was a short-segment fixation with cement-reinforced screws (Group 4), followed by long-segment fixation (Group 1). The long-segment fixation with cement-reinforced screws was the first-ranked surgical intervention for the maintenance of Cobb's angle and vertebral height, whereas the short-segment fixation performed the worst. The highest overall complication rate was in Group 6 with an incidence of 42.3% (11/26), followed by Group 2 with an incidence of 38.5% (15/39). CONCLUSION: For the treatment of VSOVCF, the short-segment fixation with cement-reinforced screws is the most effective and optimal procedure, and should be used as the preferred surgical method if surgeons are proficient in using cemented screws; otherwise, directly and unquestionably use long-segment fixation to achieve satisfactory clinical results.

The role of obesity in sarcopenia and the optimal body composition to prevent against sarcopenia and obesity.

Background: Elderly 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. Methods: Participants 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. Results: 1637 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. Conclusion: Skeletal 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.

Deciphering the "obesity paradox" in the elderly: A systematic review and meta-analysis of sarcopenic obesity.

Aging and obesity are two global concerns in public health. Sarcopenic obesity (SO), defined as the combination of age-related sarcopenia and obesity, has become a pressing issue. This systematic review and meta-analysis summarize the current clinical evidence relevant to SO. PubMed, Embase, and Web of Science were searched, and 106 clinical studies with 167,151 elderlies were included. The estimated prevalence of SO was 9% in both men and women. Obesity was associated with 34% reduced risk of sarcopenia (odds ratio [OR] 0.66, 95% CI 0.48-0.91; p < 0.001). The pooled hazard ratio (HR) of all-cause mortality was 1.51 (95% CI 1.14-2.02; p < 0.001) for people with SO compared with healthy individuals. SO was associated with increased risk of cardiovascular disease and related mortality, metabolic disorders, cognitive impairment, arthritis, functional limitation, and lung diseases (all ORs > 1.0, p < 0.05). The attenuated risk of sarcopenia in elderlies with obesity ("obesity paradox") was dependent on higher muscle mass and strength. Apart from unifying the diagnosis of SO, more research is needed to subphenotype people with obesity and sarcopenia for individualized treatment. Meanwhile, the maintenance of proper body composition of muscle and fat may delay or attenuate the adverse outcomes of aging.

Hydrogel delivery of DNase I and liposomal vancomycin to eradicate fracture-related methicillin-resistant staphylococcus aureus infection and support osteoporotic fracture healing.

Fracture-related infection (FRI) is a devastating complication in orthopedic surgery. A recent study showed that FRI causes more severe infection and further delays healing in osteoporotic bone. Moreover, bacterial biofilm formed on implants cannot be eradicated by systemic antibiotics, warranting novel treatments. Here, we developed a DNase I and Vancomycin hydrogel delivery vehicle to eradicate Methicillin-resistant Staphylococcus aureus (MRSA) infection in vivo. Vancomycin was encapsulated in liposomes, and DNase I and Vancomycin/liposomal-Vancomycin was loaded on thermosensitive hydrogel. In vitro drug release test showed a burst release of DNase I (77.2%) within 72 h and sustained release of Vancomycin (82.6%) up to day 14. The in vivo efficacy was evaluated in a clinically relevant ovariectomy (OVX) induced osteoporotic metaphyseal fracture model with MRSA infection, and a total of 120 Sprague Dawley rats were used. In the OVX with infection group, biofilm development caused a drastic inflammatory response, trabecular bone destruction, and non-union. In the DNase I and Vancomycin co-delivery hydrogel group (OVX-Inf-DVG), bacteria on bone and implant were eradicated. X-ray and micro-CT showed preservation of trabecular bone and bone union. HE staining showed the absence of inflammatory necrosis, and fracture healing was restored. The local elevation of TNF-α and IL-6 and increased number of osteoclasts were prevented in the OVX-Inf-DVG group. Our findings suggest that dual release of DNase I and Vancomycin initially followed by Vancomycin only later up to 14 days effectively eliminates MRSA infection, prevents biofilm development and provides a sterile environment to promote fracture healing in osteoporotic bone with FRI. STATEMENT OF SIGNIFICANCE: The biofilm on implants are difficult to eradicate, causing recurrent infection and non-union in fracture-related infection (FRI). Here we developed a hydrogel therapy with high in vivo efficacy to eliminate MRSA biofilm infection in a clinically-relevant FRI model in osteoporotic bone. By loading DNase I and vancomycin/liposomal-vancomycin on thermosensitive poly-(DL-lactic acidco-glycolic acid) (PLGA)-polyethylene glycol (PEG)-PLGA hydrogel, a dual release of DNase I and Vancomycin was achieved whilst preserving enzyme activity. In this model, the progressive development of infection caused a drastic inflammatory response, osteoclastogenesis, trabecular bone destruction, and non-union of fracture. These pathological changes were successfully prevented by the dual delivery of DNase I and vancomycin. Our findings provide a promising strategy for FRI in osteoporotic bone.

COVID-19 hip fracture outcomes: The role of Ct values and D-dimer levels?

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) â€‹≥ â€‹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 â€‹< â€‹30 and Ct â€‹> â€‹30, comparing their outcomes of operations performed within 48 â€‹h vs beyond 48 â€‹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 â€‹= â€‹16.00; p â€‹= â€‹0.025) in COVID-19 hip fracture patients. There was no significant difference between Ct values â€‹< â€‹30 and >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.