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Background This study was to perform an economic evaluation to understand clinical outcomes and health resource use between hip fracture patients receiving hospital-based postfracture fracture liaison service (FLS) care and those receiving usual care (UC) in Taiwan. Methods This cohort study included hospital-based data of 174 hip fracture patients who received FLS care (FLS group) from National Taiwan University Hospital, and 1697 propensity score-matched patients who received UC (UC group) of National Health Insurance claim-based data. Two groups had similar baseline characteristics but differed in hip fracture care after propensity score matching. Clinical outcomes included refracture-free survival (RFS), hip-refracture-free survival (HRFS), and overall survival (OS). Health resource use included inpatient, outpatient, and pharmacy costs within 2 years follow-up after the index of hip fracture. The economic evaluation of the FLS model was analyzed using the net monetary benefit regression framework based on the National Health Insurance perspective. Results The FLS group had longer RFS than the UC group, with an adjusted difference of 44.3 days (95% confidence interval: 7.2–81.4 days). Two groups did not differ in inpatient and outpatient costs during follow-up, but the FLS group had a higher expenditure than the UC group on osteoporosis-related medication. The probability of FLS being cost-effective was >80% and of increasing RFS, HRFS, and OS was 95%, 81%, and 80%, respectively, when the willingness-to-pay threshold was >USD 65/gross domestic product per day. Conclusion FLS care was cost-effective in reducing refracture occurrence days for patients initially diagnosed with hip fractures.

BACKGROUND The Skeletal Oncology Research Group machine-learning algorithms (SORG-MLAs) estimate 90-day and 1-year survival in patients with long-bone metastases undergoing surgical treatment and have demonstrated good discriminatory ability on internal validation. However, the performance of a prediction model could potentially vary by race or region, and the SORG-MLA must be externally validated in an Asian cohort. Furthermore, the authors of the original developmental study did not consider the Eastern Cooperative Oncology Group (ECOG) performance status, a survival prognosticator repeatedly validated in other studies, in their algorithms because of missing data. QUESTIONS/PURPOSES (1) Is the SORG-MLA generalizable to Taiwanese patients for predicting 90-day and 1-year mortality? (2) Is the ECOG score an independent factor associated with 90-day and 1-year mortality while controlling for SORG-MLA predictions? METHODS All 356 patients who underwent surgery for long-bone metastases between 2014 and 2019 at one tertiary care center in Taiwan were included. Ninety-eight percent (349 of 356) of patients were of Han Chinese descent. The median (range) patient age was 61 years (25 to 95), 52% (184 of 356) were women, and the median BMI was 23 kg/m2 (13 to 39 kg/m2). The most common primary tumors were lung cancer (33% [116 of 356]) and breast cancer (16% [58 of 356]). Fifty-five percent (195 of 356) of patients presented with a complete pathologic fracture. Intramedullary nailing was the most commonly performed type of surgery (59% [210 of 356]), followed by plate screw fixation (23% [81 of 356]) and endoprosthetic reconstruction (18% [65 of 356]). Six patients were lost to follow-up within 90 days; 30 were lost to follow-up within 1 year. Eighty-five percent (301 of 356) of patients were followed until death or for at least 2 years. Survival was 82% (287 of 350) at 90 days and 49% (159 of 326) at 1 year. The model's performance metrics included discrimination (concordance index [c-index]), calibration (intercept and slope), and Brier score. In general, a c-index of 0.5 indicates random guess and a c-index of 0.8 denotes excellent discrimination. Calibration refers to the agreement between the predicted outcomes and the actual outcomes, with a perfect calibration having an intercept of 0 and a slope of 1. The Brier score of a prediction model must be compared with and ideally should be smaller than the score of the null model. A decision curve analysis was then performed for the 90-day and 1-year prediction models to evaluate their net benefit across a range of different threshold probabilities. A multivariate logistic regression analysis was used to evaluate whether the ECOG score was an independent prognosticator while controlling for the SORG-MLA's predictions. We did not perform retraining/recalibration because we were not trying to update the SORG-MLA algorithm in this study. RESULTS The SORG-MLA had good discriminatory ability at both timepoints, with a c-index of 0.80 (95% confidence interval 0.74 to 0.86) for 90-day survival prediction and a c-index of 0.84 (95% CI 0.80 to 0.89) for 1-year survival prediction. However, the calibration analysis showed that the SORG-MLAs tended to underestimate Taiwanese patients' survival (90-day survival prediction: calibration intercept 0.78 [95% CI 0.46 to 1.10], calibration slope 0.74 [95% CI 0.53 to 0.96]; 1-year survival prediction: calibration intercept 0.75 [95% CI 0.49 to 1.00], calibration slope 1.22 [95% CI 0.95 to 1.49]). The Brier score of the 90-day and 1-year SORG-MLA prediction models was lower than their respective null model (0.12 versus 0.16 for 90-day prediction; 0.16 versus 0.25 for 1-year prediction), indicating good overall performance of SORG-MLAs at these two timepoints. Decision curve analysis showed SORG-MLAs provided net benefits when threshold probabilities ranged from 0.40 to 0.95 for 90-day survival prediction and from 0.15 to 1.0 for 1-year prediction. The ECOG score was an independent factor associated with 90-day mortality (odds ratio 1.94 [95% CI 1.01 to 3.73]) but not 1-year mortality (OR 1.07 [95% CI 0.53 to 2.17]) after controlling for SORG-MLA predictions for 90-day and 1-year survival, respectively. CONCLUSION SORG-MLAs retained good discriminatory ability in Taiwanese patients with long-bone metastases, although their actual survival time was slightly underestimated. More international validation and incremental value studies that address factors such as the ECOG score are warranted to refine the algorithms, which can be freely accessed online at https://sorg-apps.shinyapps.io/extremitymetssurvival/. LEVEL OF EVIDENCE Level III, therapeutic study.

Background To compare the risks of major osteoporotic, vertebral, and non-vertebral fractures between patients who discontinued anti-osteoporosis medications. Methods We conducted a comparative effectiveness study with a nationwide population-based cohort study design. Patients aged ≥50 years admitted between 2012 and 2015 for incident hip fractures and receiving denosumab or bisphosphonates with sufficient compliance for at least one year were included. Patients were categorized into persistent or non-persistent denosumab or bisphosphonates users based on their subsequent use pattern. The main outcomes were subsequent hospitalizations for a major osteoporotic, vertebral or non-vertebral fracture. Multivariate, time-varying Cox proportional hazards model was used to evaluate the risk of major outcomes. Results Compared with persistent denosumab users, non-persistent denosumab users had a significantly higher risk of major osteoporotic fractures (Hazard ratio (HR) = 1.60; 95% confidence interval (CI), 1.20 to 2.14),vertebral fractures (HR = 2.18; 95% CI, 1.46 to 3.24) and death (HR = 3.57; 95%CI, 2.63-4.84). However, the increased risk of fracture was not found in both persistent and non-persistent bisphosphonates users. Noteworthy, the increased risk of vertebral fractures in non-persistent denosumab users was more pronounced within one-year post discontinuation (HR = 2.90, 95% CI, 1.77 to 4.74) and among patients who discontinued from 2-year denosumab therapy (HR = 3.58; 95% CI, 1.74 to7.40). Discussion Discontinuation of denosumab resulted in an increased risk of major osteoporotic fractures, especially vertebral fractures. The increased risk tends to reveal within one-year post discontinuation and be greater after a longer treatment duration. Notably, only fracture with hospitalization was identified as our research outcome, the real risk of osteoporotic fracture post discontinuation is believed to be higher, especially for vertebral fracture. This article is protected by copyright. All rights reserved.

Due to the huge gap in the care of patients with osteoporosis and fragility fractures, we aimed to explore the effectiveness of the osteoporosis liaison service (OLS) in osteoporosis care. We found that OLS can improve osteoporosis care, including increasing medication compliance, increasing calcium/vitamin D/protein intake, and reducing fall rate. A significant gap exists in the care of patients with osteoporosis and fragility fractures. This study aimed to evaluate 1-year outcomes of an osteoporosis liaison service (OLS) program that includes two independent components: medication management services (MMS) to improve medication adherence and fracture liaison services (FLS) for secondary prevention. Patients with new hip fracture or untreated vertebral fractures enrolled in the FLS program (n = 600), and those with osteoporosis medication management issues but not necessarily fragility fractures enrolled in the MMS program (n = 499) were included. To evaluate outcomes, care coordinators assessed baseline items adapted from the 13 Best Practices Framework (BPF) standards of the International Osteoporosis Foundation, with telephone follow-up every 4 months for 1 year. Mean age of this cohort was 76.2 ± 10.3 years, 78.8% were female. After 1-year participation in the program, all patients had received bone mineral density tests, and medication adherence for the entire cohort at 12 months was 91.9 ± 19.6%, with significant improvement in fall rates (23.4% reduction), exercise rates (16.8% increase), calcium intake (26.5% increase), vitamin D intake (26.4% increase), and adequate protein intake (17.3% increase) (all p < 0.05). After 1-year OLS program, the overall rates of mortality, incident fracture, and falls were 6.6%, 4.0%, and 24.3%, respectively. The OLS program is associated with improved osteoporosis care, including increased medication adherence, calcium/vitamin D and protein intake, and reduced fall rate.

Objective To investigate the incidence and risk factors of bone cement implantation syndrome (BCIS) in bone tumor surgeries. Methods This was a retrospective observational study. We investigated patients who underwent bone tumor surgeries requiring cementation as part of the surgery between March 2016 and January 2018. We reviewed medical records, including formal anesthesia records and operation notes. Patients with complete data files were included. To investigate the general incidence of BCIS in tumor surgeries, patients of all ages, genders and tumor types were included. Vital signs, including oxygen saturation, blood pressure, heart rate, and respiratory rate, were checked and recorded once every 1–2 min after cementation. Accurate time points of cementation were recorded on formal anesthesia record sheets by the anesthesiologists. The definition and severity of BCIS were based on the classification system proposed in previous studies: grade I, moderate hypoxia (SpO2 20%); grade II, severe hypoxia (SpO2 40%) or unexpected loss of consciousness; and grade III, cardiovascular collapse requiring cardiopulmonary resuscitation. We also compared the incidence of BCIS between those patients with and without possible risk factors, including intraoperative blood loss, arthroplasty, use of an intramedullary device, patient age, gender, tumor location, and preexisting lung cancer or lung metastasis. Results A total of 88 patients were included. BCIS occurred in 23 patients, with an incidence of 26.1%. Among them, 19 had grade I and 4 had grade II BCIS. There was no patients with grade III BCIS. The lowest blood pressure occurred within 10 min in 21 (87.5%) patients and within 20 min for all patients. A total of 9 grade I BCIS were self‐limiting. The other 10 grade I hypotension cases and all grade II hypotension cases recovered after administration of a vasoconstrictor medication. Preexisting lung cancer or lung metastasis was the risk factor for BCIS; 40.0% of patients (16 in 40 patients) with preexisting lung cancer or metastasis had BCIS, whereas only 14.6% of patients (7 in 48 patients) without lung lesions had BCIS. There was no risk difference in terms of arthroplasty, old age, and increased blood loss. Apart from grades I and II bone cement implantation syndrome, there were no other major complications, including death, cardiovascular events, or cerebrovascular events. Conclusion Bone cement implantation syndrome is not unusual in bone tumor surgeries, and preexisting lung cancer or lung metastasis is a risk factor., The incidence of bone cement implantation syndrome (BCIS) in bone tumor surgeries was 26%. The incidence of grade I and grade II BCIS was 22% and 4%, respectively.

Simple Summary CARMA3 is overexpressed in most cancers, and its expression is positively associated with poor prognosis. In this study, we evaluated the detailed mechanisms of CARMA3-mediated CRC metastasis. We found that overexpression of CARMA3 induced the expression of YAP and NF-κB activation, then elicited EMT induction to enhance cell migration and invasion. We demonstrate for the first time that YAP is a critical downstream regulator of CARMA3 in CRC. Our findings reveal a regulation axis between CARMA3 and Hippo oncoprotein YAP and further support the potential role of CARMA3 in the metastasis and cancer stemness of CRC. Abstract CARD-recruited membrane-associated protein 3 (CARMA3) is overexpressed in various cancers and is associated with cancer cell proliferation, metastasis, and tumor progression; however, the underlying mechanisms of CARMA3 in colorectal cancer (CRC) metastasis remain unclear. Here, we found that higher CARMA3 expression was correlated with poor overall survival and metastasis in CRC patients from the TNMplot database and Human Tissue Microarray staining. Elevating CARMA3 expression promoted cell proliferation, epithelial-mesenchymal transition (EMT) induction, migration/invasion abilities, sphere formation, and cancer stem cell markers expression. Knockdown of CARMA3 decreased these processes via the EMT-related transcription factor Slug. Moreover, CARMA3 depletion significantly reduced tumor growth in mice that were consistent with the in vitro results. CRC migration/invasion could be regulated by CARMA3/YAP/Slug signaling axis using genetic inhibition of Yes-associated protein (YAP). Interestingly, CARMA3 induced activation of nuclear factor (NF)-κB through YAP expression, contributing to upregulation of Slug. YAP expression positively correlated with CARMA3, NF-κB, and Slug gene expression and poor clinical outcomes in CRC patients. Our findings demonstrate for the first time that CARMA3 plays an important role in CRC progression, which may serve as a potential diagnostic biomarker and candidate therapeutic target for CRC treatment.

Background: Though denosumab is an effective treatment for osteoporosis, the rebound effect after discontinuation has drawn investigators' attention. It includes a dramatic loss of gained bone mineral density (BMD) and an increased risk of vertebral fractures. This prospective multi-institutional randomized controlled trial aims to investigate whether zoledronate prevents loss of BMD after discontinuation of denosumab. The trial was registered as Denosumab Sequential Therapy (DST) trial in March 2019 at clinicaltrials.gov, with the identifier NCT03868033.Methods: The study is conducted at National Taiwan University Hospital and its branches. Patients who have continuously received denosumab treatment for two or more years are surveyed for eligibility. Baseline characteristics and questionnaires of life quality are recorded after recruitment. BMD, circulating levels of bone turnover markers (BTMs), including serum N-terminal propeptide of type 1 collagen (P1NP) and C-terminal telopeptide (CTX), are checked before the stratified randomization to 4 groups. Biological sex and the T-scores are used to create 4 strata. The participants in group 1 adhere to regular denosumab therapy for another 2 years. All the other patients receive on-time zoledronate treatment in the first year. The participants in group 2, 3, and 4 have on-time denosumab, on-time zoledronate and drug holiday in the second year, respectively. BMDs are checked annually. Pre-scheduled checkpoints of BTMs are also arranged. For patient safety, rescue treatment with another injection of zoledronate will be applied to the patients on drug holiday if the CTX levels raise above the pre-specified threshold, 0.573 ng/mL for women and 0.584 ng/mL for men. The primary outcomes are the percentage changes of BMDs in lumbar spine, total hip and femoral neck. The secondary outcomes include the changes of serum level of the BTMs, new osteoporotic fractures, extra zoledronate injections needed in group 4 and the differences of quality of life.Discussion: We aim to provide evidence whether zoledronate prevents bone loss after denosumab cessation. To our knowledge, the study has the largest sample size. No other randomized controlled study included all the three different treatment strategies and a positive control. It is also the first associated randomized controlled trial outside Europe.

Summary: Background: Atypical lipomatous tumor (ALT) is a low-grade malignancy that frequently occurs at a subfascial anatomical location. While marginal excision is adequate for lipomas, excision with a surgical margin is suggested for ALTs. However, ALTs and lipomas are difficult to differentiate preoperatively, even with the help of imaging studies. In this study, we aimed to formulate a scoring system based on selected clinical and imaging characteristics to enhance the accuracy of pre-operative diagnosis of deep-seated ALTs. Methods: We enrolled 417 cases of deep-seated lipoma and 53 cases of ALTs from soft tissue treated between 2005 and 2016. Tumors arising from the bone, internal cavities, retroperitoneum, or nervous system were excluded. Clinical data were analyzed along with magnetic resonance image (MRI) features. We further developed a scoring formula to distinguish deep-seated ALTs from lipomas. Results: Older age, tumor location at lower limbs, and the presence of MRI features (larger size, thick septa > 2 mm, contrast enhancement>1 cm, fat component

Osteoporosis medication in fragility fracture patients is associated with better outcomes. However, limited studies have investigated whether fracture types affect outcomes among patients undergoing treatment. We performed a secondary data analysis on participants from a fracture liaison service and an osteoporosis medication management service. Participants (n = 974) were regrouped into hip fracture (HF), vertebral fracture (VF), HF + VF, and NO HF/VF groups at baseline. Bivariate and multivariate logistic regressions were performed to identify baseline correlates on one-year mortality, incident refractures, and falls. Baseline characteristics were different among fracture groups. The HF group was oldest, with the lowest body mass index (BMI), lowest FRAX® T-score and had the highest 10-year fracture risk. After intervention, the HF group still had the highest mortality, but the HF + VF group had the highest refracture and incident fall rates. In the multivariate regression analysis, prevalent HF and VF, lower BMI and albumin level, and having chronic kidney disease or cancer were associated with higher mortality rates. HF + VF patients had the highest refracture risk. Prevalent HF and VF, older age and higher BMI, and having cancer or osteoarthritis were associated with a greater fall risk. HF and VF are associated with adverse outcomes, even under an optimal fracture care.

Objectives Emerging evidence has indicated a role for pharmacologic agents in the primary prevention of osteoporotic fracture, but have not yet been systematically reviewed for meta-analysis. We conducted a meta-analysis to evaluate the efficacy of pharmacologic interventions in reducing fracture risk and increasing bone mineral density (BMD) in postmenopausal women with osteopenia or osteoporosis but without prevalent fragility fracture. Method The Medline, EMBASE, and CENTRAL databases were searched from inception to September 30, 2019. Only randomized placebo-controlled trials evaluating postmenopausal women with −1.0 > bone mineral density (BMD) T-score > −2.5 (low bone mass) and those with BMD T-score ≤ −2.5 (osteoporosis) but without baseline fractures, who were receiving anti-osteoporotic agents, providing quantitative outcomes data and evaluating risk of vertebral and/or non-vertebral fragility fracture at follow-up. The PRISMA guidelines were followed, applying a random-effects model. The primary endpoint was the effect of anti-osteoporotic regimens in reducing the incidence of vertebral fractures. Secondary endpoints were percentage changes in baseline BMD at the lumbar spine and total hip at 1 and 2 years follow up. Results Full-text review of 144 articles yielded, 20 for meta-analysis. Bisphosphonates reduced the risk of vertebral fracture (pooled OR = 0.50, 95%CIs = 0.36–0.71) and significantly increased lumbar spine BMD after 1 year, by 4.42% vs placebo (95%CIs = 3.70%–5.14%). At the hip, this value was 2.94% (95%CIs = 2.13%–3.75%). Overall results of limited studies for non-bisphosphonate drugs showed increased BMD and raloxifene significantly decreases the risk of subsequent clinical vertebral fractures. Conclusion The bisphosphonates are efficacious and most evident for the primary prevention of osteoporotic vertebral fractures, reducing their incidence and improving BMD in postmenopausal women with osteopenia or osteoporosis., Highlights • Bisphosphonates reduced the risk of vertebral fracture in postmenopausal women with osteopenia or osteoporosis but without fracture. • Bisphosphonates increased BMD in postmenopausal women with osteopenia or osteoporosis but without fracture. • Limited studies for non-bisphosphonate drugs showed increased BMD in postmenopausal women with osteopenia or osteoporosis but without fracture. • Raloxifene decreased the risk of clinical vertebral fractures in postmenopausal women with osteopenia or osteoporosis but without fracture.

Background: Since 2011, Taiwan’s National Health Insurance Administration (NHIA) issued a regulation on the reimbursement to anti-osteoporosis medications (AOMs). This study aimed to evaluate the impact of this regulation in reimbursement on the utilization of AOMs, clinical outcomes and associated medical expenditures of patients with incident hip fractures. Methods: By using the National Health Insurance Research Database (NHIRD), patients with incident hip fracture from 2006 to 2015 were identified as our study cohort. Patients younger than 50 years old or prescribed with AOMs within one year prior to incident fracture were excluded. Outcomes of interest were quarterly estimates of the proportion of patients who received bone mineral density (BMD) examination, who were prescribed AOMs, as well as who encountered subsequent osteoporotic fracture-related visits and associated medical expenditures. Particularly, age- and gender specific estimates were reported. An interrupted time series study design with segmented regression model was used to quantitatively explore the impact of the changes of the reimbursement criteria on the level (immediate) and trend (long-term) changes of these outcomes. Results: Our study enrolled 118 493 patients with incident hip fracture with those patients aged older than 80 years old accounting for the largest proportion. A significantly decreased trend of AOMs prescription rates was observed immediately post regulation except for female aged between 65 and 80, while the long-term pattern showed no significant difference. However, the percentage of patients encountered subsequent osteoporotic fracture-related visit was not statistically different between pre- and post-regulation periods. Noteworthy, the policy regulation was associated with an increasing trend of osteoporotic fracture associated medical expenditures, especially for patients older than 80 years old. Conclusion: The regulation on the reimbursement for AOMs decreased the prescribing rate of AOMs immediately although the effect did not sustain thereafter. However, higher subsequent osteoporotic fracture-related medical expenditures were introduced, especially among those very old population.

Arsenic, a widely distributed toxic metalloid, has been found to be associated with the low-birth-weight infants and the impairment of muscle regenerative capacity in areas with high levels of arsenic in drinking water. The distal muscular atrophy is one of side effects of arsenic trioxide (As2O3) for acute promyelocytic leukemia therapy. We hypothesized that arsenic may be a potential risk factor for skeletal muscle atrophy. Here, we investigated the action and molecular mechanism of low-dose arsenic on the induction of skeletal muscle atrophy in a skeletal muscle cell model. The differentiated C2C12 myotubes were treated with As2O3 (0.25–1 μM) for 48 h without apparent effects on cell viability. The signaling molecules for myotube atrophy were assessed. Submicromolar-concentration As2O3 dose-dependently triggered C2C12 myotube atrophy and increased the protein expressions of atrogenes Atrogin1 and MuRF1 and inhibited the upstream phosphorylated proteins Akt and FoxO1, while As2O3 dose-dependently increased AMPK phosphorylation in myotubes. Akt activator SC79 could significantly reverse the As2O3-induced myotube atrophy. These results suggest that arsenic is capable of inducing myotube atrophy by inhibiting an Akt signaling pathway.

Background: The deterioration of the musculoskeletal system imposes significant impact on physical activity. Exercise is an important strategy which minimizes these changes. It is not clear which type of exercise provides better improvement on low physical performance, low muscle mass and low strength of sarcopenia. We aim to develop an integrated care (IC) model and compare its relative efficacy in limb fat free mass, muscle strength, and physical performance with low extremities exercise (LEE) in community dwelling older adults with high risk of fractures (Fracture Risk Assessment Tool (FRAX®)) ≧3% for hip fracture, ≧20% for major osteoporotic fracture or 1-min osteoporosis risk test (≧1 point) or fall (≧2 falls in previous year). Methods: Patients were assigned randomized to participate in either IC or LEE group (n = 55 each) for 3 months. All participants received education including home-based exercise. The IC group consisted of different modalities of exercise while the LEE group performed machine-based low extremities exercise. Fat free mass, muscle strength, and physical performance were measured at their baseline and 3-months follow-up. Results: Mean age was 73.8 ± 7 years with 69.1% women. Entire cohort demonstrated significant increment in fat free mass, muscle strength (4 indicators) and physical performance (3 indicators). However, between group differences were not significant. Conclusion: With regular supervise exercise; both groups are equally effective in decreasing fat mass and increasing physical performance, muscle mass and strength. However, the IC group required fewer resources and thus more financially feasible in a community setting. Keywords: Bone mineral density, Gender differences, Integrated care, Low extremities exercise, Muscle strength

Background A global consensus on the loss of skeletal muscle mass and function in humans refers as sarcopenia and cachexia including diabetes, obesity, renal failure, and osteoporosis. Despite a current improvement of sarcopenia or cachexia with exercise training and supportive therapies, alternative and specific managements are needed to discover for whom are unable or unwilling to embark on these treatments. Alendronate is a widely used drug for osteoporosis in the elderly and postmenopausal women. Osteopenic menopausal women with 6 months of alendronate therapy have been observed to improve not only lumbar bone mineral density but also handgrip strength. However, the effect and mechanism of alendronate on muscle strength still remain unclear. Here, we investigated the therapeutic potential and the molecular mechanism of alendronate on the loss of muscle mass and strength in vitro and in vivo. Methods Mouse myoblasts and primary human skeletal muscle-derived progenitor cells were used to assess the effects of low-dose alendronate (0.1-1 μM) combined with or without dexamethasone on myotube hypertrophy and myogenic differentiation. Moreover, we also evaluated the effects of low-dose alendronate (0.5 and 1 mg/kg) by oral administration on the limb muscle function and morphology of mice with denervation-induced muscle atrophy and glycerol-induced muscle injury. Results Alendronate inhibited dexamethasone-induced myotube atrophy and myogenic differentiation inhibition in mouse myoblasts and primary human skeletal muscle-derived progenitor cells. Alendronate significantly abrogated dexamethasone-up-regulated sirtuin-3 (SIRT3), but not SIRT1, protein expression in myotubes. Both SIRT3 inhibitor AKG7 and SIRT3-siRNA transfection could also reverse dexamethasone-up-regulated atrogin-1 and SIRT3 protein expressions. Animal studies showed that low-dose alendronate by oral administration ameliorated the muscular malfunction in mouse models of denervation-induced muscle atrophy and glycerol-induced muscle injury with a negative regulation of SIRT3 expression. Conclusions The putative mechanism by which muscle atrophy was improved with alendronate might be through the SIRT3 down-regulation. These findings suggest that alendronate can be a promising therapeutic strategy for management of muscle wasting-related diseases and sarcopenia.

Fracture liaison services (FLS), implemented in different ways and countries, are reported to be a cost-effective or even a cost-saving secondary fracture prevention strategy. This presumed favorable cost-benefit relationship is encouraging and lends support to expanded implementation of FLS per International Osteoporosis Foundation Best Practice Standards. This study summarizes the economic impact and cost-effectiveness of FLS implemented to reduce subsequent fractures in individuals with osteoporosis. This systematic review identified studies reporting economic outcomes for FLS in osteoporotic patients aged 50 and older through a comprehensive search of MEDLINE, EMBASE, Cochrane Central, and PubMed of studies published January, 2000 to December, 2016. Grey literature (e.g., Google scholar, conference abstracts/posters) were also hand searched through February 2017. Two independent reviewers screened titles and abstracts and conducted full-text review on qualified articles. All disagreements were resolved by discussion between reviewers to reach consensus or by a third reviewer. In total, 23 qualified studies that evaluated the economic aspects of FLS were included: 16 cost-effectiveness studies, 2 cost-benefit analyses, and 5 studies of cost savings. Patient populations varied (prior fragility fracture, non-vertebral fracture, hip fracture, wrist fracture), and FLS strategies ranged from mail-based interventions to comprehensive nurse/physician-coordinated programs. Cost-effectiveness studies were conducted in Canada, Australia, USA, UK, Japan, Taiwan, and Sweden. FLS was cost-effective in comparisons with usual care or no treatment, regardless of the program intensity or the country in which the FLS was implemented (cost/QALY from $3023-$28,800 US dollars (USD) in Japan to $14,513-$112,877 USD in USA. Several studies documented cost savings. FLS, implemented in different ways and countries, are reported to be cost-effective or even cost-saving. This presumed favorable cost-benefit relationship is encouraging and lends support to expanded implementation of FLS per International Osteoporosis Foundation Best Practice Standards.

Skeletal muscle disorders including sarcopenia are prevalent during the complex biological process of aging. Loss of muscle mass and strength commonly seen in sarcopenia is induced by impaired neuromuscular innervation, transition of skeletal muscle fiber type, and reduced muscle regenerative capacity, all attributable to chronic inflammation, oxidative stress, and mitochondrial dysfunction. Current literature suggests that vitamin E molecules (α-, β-, γ-, δ-tocopherols and the corresponding tocotrienols) with their antioxidant and anti-inflammatory capabilities may mitigate age-associated skeletal dysfunction and enhance muscle regeneration, thus attenuating sarcopenia. Preclinical and human experimental studies show that vitamin E benefits myoblast proliferation, differentiation, survival, membrane repair, mitochondrial efficiency, muscle mass, muscle contractile properties, and exercise capacity. Limited number of human cross-sectional observational studies reveal positive associations between serum tocopherol level and muscle strength. Several factors, including difficulties in validating vitamin E intake and deficiency, variations in muscle-protective activity and metabolism of diverse forms of vitamin E, and lack of understanding of the mechanisms of action, preclude randomized clinical trials of vitamin E in people with sarcopenia. Future research should consider long-term clinical trials of with adequate sample size, advanced imaging technology and omics approaches to investigate underlying mechanisms and assess clinically meaningful parameters such as muscle strength, physical performance, and muscle mass in sarcopenia prevention and/or treatment.

We proposed a new method to augment the traditional sliding hip screw (SHS) with cerclage reconstruction plates to treat pathologically impending and actual peritrochanteric fractures as well as to revise open reductions and internal fixations to increase the construct strength against the shearing force, thus reducing the implant failure rate. In this retrospective study, patients with peritrochanteric pathology with at least two years of follow-up who underwent augmentation with cerclage reconstruction plates (modified SHS) and conventional SHS between 1 May 2015 and 31 May 2017 were divided into groups A (n = 12) and B (n = 28), respectively. Demographic data, surgery duration, blood loss, complications, and local radiotherapy were analyzed. The average surgery duration was significantly longer in group A (p = 0.013). The estimated intraoperative and perioperative blood losses were not significantly different between the groups. The implant survival rates were not significantly different under competing risk analysis. The success rate of a revision surgery with modified SHS was excellent, and implant survival time was &gt, 2 years, as observed with the previous SHS constructs. Subtrochanteric region involvement and a postoperative visual analog scale ≥4 could be risk factors of implant failure and revision surgery. This technique can be an alternative treatment for difficult pathologic peritrochanteric fractures, especially those with previous plating failure.

Osteoporosis, a degenerative bone disease, is characterized by low bone mass and microstructural deterioration of bone tissue resulting in aggravated bone fragility and susceptibility to fractures. The trend of extended life expectancy is accompanied by a rise in the prevalence of osteoporosis and concomitant complications in the elderly population. Epidemiological evidence has shown an association between vitamin E consumption and the prevention of age-related bone loss in elderly women and men. Animal studies show that ingestion of vitamin E, especially tocotrienols, may benefit bone health in terms of maintaining higher bone mineral density and improving bone microstructure and quality. The beneficial effects of tocotrienols on bone health appear to be mediated via antioxidant/anti-inflammatory pathways and/or 3-hydroxy-3-methylglutaryl coenzyme A mechanisms. We discuss (1) an overview of the prevalence and etiology of osteoporosis, (2) types of vitamin E (tocopherols versus tocotrienols), (3) findings of tocotrienols and bone health from published in vitro and animal studies, (4) possible mechanisms involved in bone protection, and (5) challenges and future direction for research.

Chondrosarcoma is a malignant primary bone tumor. Sirtuin-1 (SIRT1), which is a member of sirtuin family, plays a dual role either in cancer promotion or suppression. There is no report about the role of SIRT1 in the human chondrosarcoma cells. Resveratrol is a potent activator of SIRT1. However, its effects on chondrosarcoma have not been extensively studied. Here, we investigated the role of SIRT1 induction by resveratrol in human chondrosarcoma cell growth and tumor progression. Resveratrol significantly decreased cell viability and induced cell apoptosis in human chondrosarcoma cells in a dose-dependent manner. The protein expression and activity of SIRT1 were activated after treatment with resveratrol. Resveratrol significantly inhibited NF-κB signaling by deacetylating the p65 subunit of NF-κB complex, which could be reversed by siRNA-SIRT1 transfection or deacetylation inhibitor MS-275. Resveratrol induced-apoptosis involved a caspase-3-mediated mechanism. Both siRNA-SIRT1 transfection and MS-275 significantly inhibited the resveratrol-induced caspase-3 cleavage and activity in human chondrosarcoma cells. Moreover, in vivo chondrosarcoma xenograft study revealed a dramatic reduction in tumor volume and the increased SIRT1 and cleaved caspase-3 expressions in tumors by resveratrol treatment. These results suggest that resveratrol induces chondrosarcoma cell apoptosis via a SIRT1-activated NF-κB deacetylation and exhibits anti-chondrosarcoma activity in vivo.

The epidemiological and experimental evidence suggests that diabetes can be an independent risk factor for osteoarthritis. The osteoarthritis-like cartilage damage has been shown in streptozotocin-induced diabetic mice. The therapeutic effects of human skeletal muscle-derived progenitor cells (HSMPCs) on diabetic osteoarthritis still remain unclear. Here, we investigated the therapeutic potential of HSMPCs on diabetic knee osteoarthritis. The in vitro chondrogenic ability of HSMPCs was determined by pellet culture assay. Male mice were used to develop the model of streptozotocin-induced type 1 diabetes and its related osteoarthritis. HSMPCs were injected intra-articularly to rescue osteoarthritis. Protein expressions of advanced glycation end-products, cyclooxygenase-2, and type-2 collagen in tissues were determined by immunohistochemistry. The pellet culture assay showed that HSMPCs cultured in differentiation medium for chondrogenesis significantly produced larger pellets with an overproduction of extracellular matrix than in growth medium. In in vivo experiments, intra-articular injection of HSMPCs for 4 weeks significantly prevented the progression of degenerative changes in the cartilage of streptozotocin-induced diabetic mice, including an obvious increase of total articular cartilage thickness and a decrease of fibrous cartilage thickness. HSMPCs transplantation also exerted the decline in advanced glycation end-products and cyclooxygenase-2 protein expression, but increased the type-2 collagen protein expression in streptozotocin-induced osteoarthritic cartilages. Moreover, HSMPCs transplantation also inhibited the increased serum interleukin-6 and matrix metalloproteinase-3 levels in diabetic mice. These results demonstrated for the first time that HSMPCs transplantation ameliorates cartilage degeneration in diabetes-related osteoarthritis mice. These findings suggest that HSMPCs transplantation may apply as a potential therapeutic use of diabetes-related osteoarthritis. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:1886-1893, 2017.

Osteoporosis is a major health issue. By 2050, a greater than 2-fold increase in patients number with hip fractures will occur in Asia representing 50% of all hip fractures worldwide. For the Asia-Pacific (AP) region, more efforts on controlling osteoporosis and the subsequent fractures are crucial. Bone mineral density (BMD) by dual energy X-ray absorptiometry (DXA) is commonly used to diagnose osteoporosis and monitor osteoporosis treatment. However, the inconvenience, cost, limited availability of DXA and the delay in detection of BMD changes after treatment initiation support an important role for bone turnover markers (BTMs), as short-term tools to monitor therapy. With regards to low adherence rates of medical treatment of osteoporosis, the experts reached consensus on the use of BTMs for both raising awareness and short-term monitoring of osteoporosis treatment in the AP region. The experts endorse the use of BTMs, especially serum C-terminal telopeptide of type 1 collagen (CTX) and serum procollagen type 1 N propeptide (P1NP), as short-term monitoring tools to help clinicians assess the responses to osteoporosis therapies and appropriately adjust treatment regimens earlier than BMD. Either the absolute values or the degree of change from baseline in BTMs can be used to monitor the potential efficacy of osteoporosis therapies. The use of BTMs can be incorporated in osteoporosis care programs, such as fracture liaison service (FLS), to improve patient adherence and treatment outcomes. Encouraging sufficient reimbursement from health care systems may facilitate widespread use of BTMs in clinical practice in the AP region.

Background Exercise, nutrition, and psychological interventions may all have positive impacts on frailty and sarcopenia. However, it is not known whether an integrated care programme with all three components can be beneficial and the intensity of such programme is also not certain. In this study, we aim to determine the effectiveness of two levels of integrated care on frailty and sarcopenia. Methods A randomized control trial was conducted at two community hospitals in Taiwan. Older adults (65–79 years of age, N = 289) who scored ≥1 on the Cardiovascular Health Study Phenotypic Classification of Frailty (CHS_PCF) were enrolled in the trial. Low-level care (LLC) participants received a 2 h education course on frailty, sarcopenia, coping strategy, nutrition, and demonstration of study exercise programme. Educational multimedia material was distributed as reference for home practice with bi-monthly telephone follow-ups on adherences. High-level care (HLC) participants, in addition to LLC instructions, received six sessions of on-site problem solving therapy and 48 exercise sessions within 6 months. Brief nutrition consultation was also provided during the exercise sessions. Primary outcome was improvement of the CHS_PCF by at least one category (from pre-frail to robust, or from frail to pre-frail or robust) from baseline. Secondary outcomes included changes of individual frailty, and sarcopenia indicators. Assessments were done at 3, 6, and 12 months by trained research assistants blinded to randomization status. Intention-to-treat analysis was applied. Results Mean age was 71.6 ± 4.3 years, with 53% females. For the entire cohort, improvement of primary outcome was 35% at 3 months, increased to 40% at 6 months, and remained stable at 39% at 12 months. Improvement rates were similar in both groups. Compared with the LLC group, HLC participants had greater improvements in the following indices: energy expenditure of walking, 5 m walking time, dominant hand grip strength, timed-up-and-go-test, and one-leg-stand time — mainly at 6 and 12 month assessments. Conclusions The 6 month integrated care improved frailty and sarcopenia status among community-dwelling elders, with high-intensity training yielding greater improvements. Low-level care could be promoted as a basic intervention, while HLC could be reserved for those at high risk and with high motivation.

Diabetic myopathy, a less studied complication of diabetes, exhibits the clinical observations characterized by a less muscle mass, muscle weakness and a reduced physical functional capacity. Accumulation of advanced glycation end-products (AGEs), known to play a role in diabetic complications, has been identified in ageing human skeletal muscles. However, the role of AGEs in diabetic myopathy remains unclear. Here, we investigated the effects of AGEs on myogenic differentiation and muscle atrophy in vivo and in vitro. We also evaluated the therapeutic potential of alagebrium chloride (Ala-Cl), an inhibitor of AGEs. Muscle fibre atrophy and immunoreactivity for AGEs, Atrogin-1 (a muscle atrophy marker) and phosphorylated AMP-activated protein kinase (AMPK) expressions were markedly increased in human skeletal muscles from patients with diabetes as compared with control subjects. Moreover, in diabetic mice we found increased blood AGEs, less muscle mass, lower muscular endurance, atrophic muscle size and poor regenerative capacity, and increased levels of muscle AGE and receptor for AGE (RAGE), Atrogin-1 and phosphorylated AMPK, which could be significantly ameliorated by Ala-Cl. Furthermore, in vitro, AGEs (in a dose-dependent manner) reduced myotube diameters (myotube atrophy) and induced Atrogin-1 protein expression in myotubes differentiated from both mouse myoblasts and primary human skeletal muscle-derived progenitor cells. AGEs exerted a negative regulation of myogenesis of mouse and human myoblasts. Ala-Cl significantly inhibited the effects of AGEs on myotube atrophy and myogenesis. We further demonstrated that AGEs induced muscle atrophy/myogenesis impairment via a RAGE-mediated AMPK-down-regulation of the Akt signalling pathway. Our findings support that AGEs play an important role in diabetic myopathy, and that an inhibitor of AGEs may offer a therapeutic strategy for managing the dysfunction of muscle due to diabetes or ageing.

Objective The optimal time after hip fracture to start prophylactic anti-osteoporosis medications (AOMs) remains uncertain, especially in real-world practice. Therefore, we investigated how timing of AOMs initiation affects the risk of subsequent osteoporotic fractures, and what factors influence timing of AOMs prescription. Method Patients ≥50 years old with diagnostic codes indicating hospitalization for hip fracture (n = 77,930) were identified from the Taiwan National Health Insurance Research Database; 9986 who were prescribed AOMs ≤1 year after a newly-diagnosed hip fracture were grouped into those who started AOMs from: ≤14 days (very early); 15–84 days (early); 85–252 days (late); and 253–365 days (very late). Associations with fracture-related hospitalizations after an index fracture were analyzed using a multivariate, time-dependent Cox proportional hazards model, and between-group differences compared by log-rank testing. Factors influencing timing of AOMs initiation were elucidated using multivariate logistic regression analyses. Results Compared to AOMs initiation from 15 to 84 days, initiation after 252 days was associated with significantly increased risk of fracture-related hospitalization (HR = 1.93, 95% CI 1.29–2.89). Both sensitivity and pre-specified subgroup analyses yield similar results. Among patients with high adherence to AOMs, the increased risk of subsequent fracture-related hospitalization among very late users was profound (HR = 2.56, 95% CI 1.41–4.64). Conclusion Timing of AOMs initiation was significantly associated with age, index year, index hospital length of stay as well as the accreditation level and geographic region of index hospital. After adjusting factors associated with timing of AOMs initiation and patients' adherence, the anti-fracture benefit of AOMs still depends crucially on the timely initiation of AOMs.

Objective A fracture liaison service (FLS) for patients with fractures is a promising approach for improving outcomes, but barriers to the successful implementation of an FLS remain. The factors influencing the outcomes of patients already receiving FLS care are unclear. Design A prospective multicenter cohort study. Settings and participants Patients with incident hip and clinical vertebral fractures treated at 2 institutions between January 2014 and June 2016 were prospectively enrolled. Demographic profiles, comorbidities, prior fracture experiences, T scores, Fracture Risk Assessment Tool (FRAX) scores, and serum markers were examined. Measures Self-reported functional status (at the 4th month), mortality, recurrent fractures, and falls (at the 2-year follow-up). Results Of 712 patients screened for eligibility, 600 (84%) participants (age 78 ± 10 years) were enrolled in the FLS program. At 4 months, 58%, 53%, and 60% of the participants reported improved mobility, self-care, and daily activities after FLS care, respectively. After 2 years, 85 (14%) died, 36 (6%) developed recurrent fractures, and 199 (33%) had 1 or more fall episodes. Multivariate logistic regression showed that neurologic disorders, heart disease, and diabetes were associated with a decreased probability of functional recovery. Cox regression showed that older age and chronic kidney disease (CKD) were predictive of increased mortality, whereas heart disease was correlated with an increased refracture risk. Older age and cancer or osteoarthritis were associated with a higher risk of falls. Importantly, a higher body mass index predicted a lower risk of mortality and a higher probability of improved self-care but a higher risk of fall at follow-up. Conclusions/Implications We discovered that comorbidities including CKD, heart disease, cancer, and osteoarthritis could influence short-term functional changes, survival, and the risk of refractures or falls among patients participating in FLSs. These factors are expected to aid in prognosis estimation and management planning for those with fractures.

Patient-reported experience measures (PREMs) are integral component of care for fracture patients. Using a multicenter cohort, we showed that the presence of chronic kidney disease (CKD) attenuated the probability of PREM improvement in fracture patients. Assessing PREM can assist physicians in improving patients’ experiences. Patients with CKD are at an increased risk of exhibiting poor PREM and developing fractures. We aimed to assess whether CKD influences the probability of PREM improvement during follow-up among patients with fractures. We prospectively enrolled patients with hip or vertebral fractures from different institutes into a fracture liaison service program. After registering clinical histories, they received a baseline PREM assessment based on EuroQol group–5 dimension content, including self-care, daily activity, and pain severity using a 5-point Likert scale. A follow-up PREM assessment was arranged 4 months later, and we evaluated whether baseline CKD was predictive of PREM improvement. Among 593 fracture patients (18% with CKD), 37.3% and 62.7% presented with hip and vertebral fractures, respectively. Self-care, daily activity, and pain severity improved after follow-up in 32%, 27%, and 43% participants; those with CKD exhibited worse self-care ability and daily activity than those without. Multivariate logistic regression analyses showed that baseline CKD was significantly associated with lower possibility of improvement in daily activity (odds ratio [OR] 0.58, p = 0.049) and pain severity (OR 0.52, p = 0.01), and an insignificant change in the possibility of improvement in self-care ability (OR 0.61, p = 0.09). The presence of CKD predicts a significantly lower probability of PREM improvement among fracture patients. An early emphasis on renal function during fracture care should be considered.

This nationwide cohort study examined the potential disease-modifying effect of anti-osteoporosis medication on hip osteoarthritis. The results revealed that the usage of anti-osteoporosis medication is not associated with decreased risk in undergoing total hip arthroplasty in patient with hip osteoarthritis. This study aimed to assess the association between use of anti-osteoporosis medications (AOMs) and the risk of undergoing total hip arthroplasty (THA) in patients with hip osteoarthritis (OA). Using the 2008–2013 National Health Insurance Research Database, we identified patients who were first diagnosed as having hip OA. All identified patients were followed until THA, death of any cause, or December 31, 2013, whichever occurred first. All AOM exposures were divided into three categories: bisphosphonates use, non-bisphosphonates use, and no use of AOMs and assessed in a time-varying manners. The primary outcome was THA. The secondary outcome was the differences in the longitudinal utilization of NSAIDs between AOM users and non-users. Time-dependent Cox proportional hazards models were used to investigate the effect of AOM use on the risk of THA. We identified 35,870 patients who were first diagnosed as having hip OA and had no history of AOM use between 2009 and 2012. Among them, 3162 and 1667 patients had their first prescription of bisphosphonates and other non-bisphosphonates AOMs during the follow-up period. Mean age of bisphosphonates users, non-bisphosphonates users, and non-users was 75.62, 76.84, and 67.39 years, respectively. Bisphosphonates or non-bisphosphonates users did not show significant change when compared to non-users in terms of risk of undergoing THA [adjusted hazard ratio (aHR) 0.972, 95% confidence interval (CI) 0.743–1.273; aHR 0.926, 95% CI 0.672–1.277]. Our results showed that the use of AOMs is not associated with decreased risk of THA in patients with hip OA.

Osteosarcoma is the most common bone malignancy that occurs in the young population. After osteosarcoma cells metastasize to the lung, prognosis is very poor owing to difficulties in early diagnosis and effective treatment. Recently, connective tissue growth factor (CTGF) was reported to be a critical contributor to osteosarcoma metastasis. However, the detailed mechanism associated with CTGF-directed migration in bone neoplasms is still mostly unknown. Through the in vivo and in vitro examination of osteosarcoma cells, this study suggests that VCAM-1 up-regulation and increased osteosarcoma cell migration are involved in this process. Antagonizing αvβ3 integrin inhibited cell migration. Moreover, FAK, PI3K, Akt and NF-κB activation were also shown to be involved in CTGF-mediated osteosarcoma metastasis. Taken together, CTGF promotes VCAM-1 production and further induces osteosarcoma metastasis via the αvβ3 integrin/FAK/PI3K/Akt/NF-κB signaling pathway, which could represent a promising clinical target to improve patient outcome.

Background Aging-related loss of muscle and strength with increased adiposity is prevalent among older people in long-term care (LTC) facilities. Studies have shown that people with sarcopenic obesity (SO) are at high risk of declining physical performance. At present, no interventional studies on residents with SO in nursing homes have been conducted in the literature. The objectives of this study include appraising the changes in body composition and physical performance following resistance training among residents with SO in LTC facilities. Methods This study used a quasiexperimental research design. Residents who are 60 years of age or above and have been living a sedentary lifestyle in LTC facilities for the past 3 months will be eligible for inclusion. The intervention group engaged in chair muscle strength training twice a week for 12 weeks, whereas the control group underwent the usual care. The main variables were physical parameters of being lean and fat, the strength of grip and pinch, and a functional independence measure using descriptive analysis, chi-squared test, t-test, and generalized estimating equation for statistical analysis through SPSS. Results A total of 64 respondents with SO completed the study. After training, total grip strength (p = 0.001) and total pinch strength (p = 0.014) of the intervention group differed significantly from those of the control group. The right grip strength of the intervention group increased by 1.71 kg (p = 0.003) and the left grip strength improved by 1.35 kg (p = 0.028) compared with baseline values. The self-care scores of the intervention group increased by 2.76 points over baseline scores, particularly for the action of dressing oneself. Although grip strength and self-care scores improved more among those in the intervention group, body fat and skeletal muscle percentages did not differ significantly between the groups after training (p > 0.05). Conclusions Resistance exercises for elderly residents in LTC facilities may play an important role in helping them maintain physical well-being and improve muscle strength. Trial registration Clinicaltrials.gov, number NCT02912338 . Retrospectively registered on 09/21/2016.

Background Studies have shown that sarcopenia easily leads to difficulty moving, disability, and poor quality of life. However, researches on the use of whole-body vibration for older adults with sarcopenia living in institutions have been lacking. Therefore, the main objective of the present study was to investigate the effect of whole-body vibration intervention on improving the skeletal muscle mass index, physical fitness, and quality of life of older adults with sarcopenia living in institutions. Methods This study adopted a quasi-experimental, single-group, pretest-posttest design. The whole-body vibration intervention was performed over a 3-month period, in which the older adults trained 3 times per week; each training lasted 60 s with a break of 30 s for 10 repetitions. The older adults’ skeletal muscle mass index, physical fitness and quality of life before and after the intervention of the whole-body vibration was collected. Concerning the statistical methods adopted, nonparametric method-based tests were employed. Results According to the results of analysis, after the intervention of the 12-week whole-body vibration, the skeletal muscle mass index (z = − 3.621, p = 0.000), physical fitness on standing on one foot (z = − 2.447, p = 0.014), shoulder–arm flexibility (z = − 3.159, p = 0.002), 8-ft up and go test (z = − 2.692, p = 0.009), hand grip strength (z = − 3.388, p = 0.009), and five repeated sit-to-stand tests (z = − 2.936, p = 0.003), all improved significantly. Furthermore, concerning the quality of life of the older adults in the pretest and posttest, the improvements were statistically significant (z = − 2.533, p = 0.011). Conclusions The study results showed the effect of whole-body vibration intervention on improving the skeletal muscle mass index, physical fitness, and quality of life of sarcopenic older people living in institutions and could serve as a crucial reference to health care professionals.

The classic suprascapular nerve block has limitations, such as postural requirements and lack of direct nerve visualization. This series investigated the analgesic effect of ultrasound-guided supraclavicular suprascapular nerve blocks in patients with malignancy-associated shoulder pain. Ablative radiofrequency lesioning of the suprascapular nerve in 6 patients provided substantial pain relief. The mean distance from the suprascapular nerve to the brachial plexus was 8.05 mm, and the mean angle of needle entry was 20.6°. This approach appears to be effective in relieving malignancy-associated shoulder pain and is tolerated by patients unable to sit or lie prone.

As human beings live longer, age-related diseases such as osteoporosis will become more prevalent. Intolerant side effects and poor responses to current treatments are observed. Therefore, novel effective therapeutic agents are greatly needed. Here, pyrazole derivatives were designed and synthesized, and their osteoclastogenesis inhibitory effects both in vitro and in vivo were evaluated. The most promising compound 13 with a 2-(dimethylamino)ethyl group inhibited markedly in vitro osteoclastogenesis as well as the bone resorption activity of osteoclasts. Compound 13 affected osteoclast's early proliferation and differentiation more than later fusion and maturation stages. In ovariectomized (OVX) mice, compound 13 can inhibit the loss of trabecular bone volume, trabecular bone number, and trabecular thickness. Moreover, compound 13 can antagonize OVX-induced reduction of serum bone resorption marker and then compensatory increase of the bone formation marker. To sum up, compound 13 has high potential to be developed into a novel therapeutic agent for treating osteoporosis in the future.

Background Epidemiological studies have reported that the prevalence of diabetes in women > 40 years of age, especially those in the postmenopausal phase, was higher than in men in areas with high levels of arsenic in drinking water. The detailed effect of arsenic on glucose metabolism/homeostasis in the postmenopausal condition is still unclear. Objectives We investigated the effects of arsenic at doses relevant to human exposure from drinking water on blood glucose regulation in estrogen-deficient female mice. Methods Adult female mice who underwent ovariectomy or sham surgery were exposed to drinking water contaminated with arsenic trioxide (0.05 or 0.5 ppm) in the presence or absence of 17β-estradiol supplementation for 2–6 weeks. Assays related to glucose metabolism were performed. Results Exposure of sham mice to arsenic significantly increased blood glucose, decreased plasma insulin, and impaired glucose tolerance, but did not induce insulin resistance. Blood glucose and insulin were higher, and glucose intolerance, insulin intolerance, and insulin resistance were increased in arsenic-treated ovariectomized mice compared with arsenic-treated sham mice. Furthermore, liver phosphoenolpyruvate carboxykinase (PEPCK) mRNA expression was increased and liver glycogen content was decreased in arsenic-treated ovariectomized mice compared with arsenic-treated sham mice. Glucose-stimulated insulin secretion in islets isolated from arsenic-treated ovariectomized mice was also significantly decreased. Arsenic treatment significantly decreased plasma adiponectin levels in sham and ovariectomized mice. Altered glucose metabolism/homeostasis in arsenic-treated ovariectomized mice was reversed by 17β-estradiol supplementation. Conclusions Our findings suggest that estrogen deficiency plays an important role in arsenic-altered glucose metabolism/homeostasis in females. Citation Huang CF, Yang CY, Chan DC, Wang CC, Huang KH, Wu CC, Tsai KS, Yang RS, Liu SH. 2015. Arsenic exposure and glucose intolerance/insulin resistance in estrogen-deficient female mice. Environ Health Perspect 123:1138–1144; http://dx.doi.org/10.1289/ehp.1408663

Background: The treatment of adhesive capsulitis is a dilemma for orthopaedic rehabilitation specialists. In this study, we assessed whether extracorporeal shockwave therapy (ESWT) improves the functional outcome of primary shoulder adhesive capsulitis. Methods: In this prospective, randomized, controlled, single-blind clinical trial, we enrolled 40 patients with primary adhesive capsulitis to assess whether ESWT can improve the functional outcome of primary adhesive capsulitis better than oral steroid therapy. Patients were allocated to the oral steroid group or ESWT group with randomization. Functional outcome evaluations were performed using the Constant Shoulder Score (CSS) and Oxford Shoulder Score. Results: Both groups showed significant improvement in the Oxford Shoulder Score evaluation throughout the study period. In the ESWT group, the total CSS and range of motion (ROM) parameter of the CSS in the ESWT group showed significant improvement from the fourth week that was better than that in the steroid group; the activities‐of‐daily living (ADL) parameter of the CSS achieved significance and was better than that in the steroid group at the sixth week. For the steroid group, pain was significantly reduced from baseline to the fourth week of the study; ADL and ROM improved at the fourth to 12th week. For the ESWT group, ADL and ROM improvements were significant from baseline to the sixth week. Conclusion: Our results showed that ESWT can be an alternative treatment, at least in the short-term, for primary adhesive capsulitis of the shoulder. In addition, all of the side effects of ESWTwere transient and tolerable.

This nationwide study investigated the epidemiology, treatment patterns, and economic burden of osteoporosis and associated fracture in Taiwan. The treatment of osteoporosis is alarmingly suboptimal, considering the significantly increased economic burden of major osteoporotic fracture. Osteoporosis men received lesser anti-osteoporosis drugs but had higher incremental costs attributable to osteoporotic fractures. This nationwide study investigated the epidemiology, treatment patterns, and economic burden of osteoporosis and associated fracture between 2009 and 2013 in Taiwan. We used the National Health Insurance Research Database as our data source. The prevalence of diagnosed osteoporosis and major osteoporotic fractures was calculated annually from 2009 to 2013, stratified by age and gender. Osteoporosis patients who received any prescription of anti-osteoporosis drugs during each fiscal year were defined as osteoporosis patients under treatment. Healthcare utilization and associated direct medical costs were used to quantify the economic burden of osteoporosis. For patients who encountered major osteoporotic fracture, the incremental changes of direct medical costs attributable to fracture using a pre- and post-quasi-experimental design were estimated. Furthermore, we compared the annual direct medical costs of patients who encountered major osteoporotic fracture with those diagnosed osteoporosis only and with the general population. The prevalence of diagnosed osteoporosis increased with age, with the highest rate among those aged 80 and older. Overall, less than one-third of women and only 10% of men received anti-osteoporosis drugs among osteoporosis patients. The annual direct medical costs for osteoporosis patients increased steadily from 2009 to 2013. The total medical costs and incremental change of direct medical costs were higher in men than those in women. We found the treatment of osteoporosis to be alarmingly suboptimal, considering the significantly increased economic burden of major osteoporotic fracture also identified in this study. Osteoporosis men received lesser anti-osteoporosis drugs but had higher incremental costs attributable to major osteoporotic fractures.

BACKGROUND The use of bisphosphonates has been reported to have potential beneficial effects on knee osteoarthritis, but existing studies have limitations. The purpose of this study was to examine the association of bisphosphonate use with the risk of undergoing total knee arthroplasty and with the consumption of pain medication among osteoporotic patients with knee osteoarthritis. METHODS We identified patients who were newly diagnosed with knee osteoarthritis among a cohort of patients with osteoporosis from 2009 to 2012 in the National Health Insurance Research Database in Taiwan. We further categorized these patients into 2 groups: those who were treated with bisphosphonates (bisphosphonate users) and those who were not treated with any anti-osteoporosis drug (nonusers). Bisphosphonate treatment adherence was calculated by the medication possession ratio (MPR) as the proportion of days of bisphosphonate treatment within a fixed duration; an MPR of ≥80% was considered high adherence. The primary and secondary outcomes of interest were undergoing total knee arthroplasty and the use of pain medication, respectively. Analyses using Cox proportional hazard models with propensity-score adjustment were performed to estimate the association between bisphosphonate use and the risk of undergoing total knee arthroplasty. The incremental change in the mean accumulated defined daily doses of pain medications among both bisphosphonate users and nonusers was calculated. RESULTS We identified 16,276 bisphosphonate users and 123,791 nonusers of any anti-osteoporosis drug among the patients with osteoporosis who were newly diagnosed with osteoarthritis. Bisphosphonate use was significantly associated with a decreased risk of total knee arthroplasty (adjusted hazard ratio [HR], 0.76; 95% confidence interval [CI], 0.69 to 0.83; p < 0.001). In patients with a follow-up period of ≥24 months and an MPR of ≥80%, the effect size was significantly greater (adjusted HR, 0.66; p = 0.048). Over the 5 years of follow-up, we found a significantly greater decrease in the use of pain medication among bisphosphonate users than among nonusers (p < 0.001; Chow test). CONCLUSIONS Among patients with osteoporosis and osteoarthritis, bisphosphonate use was associated with a significantly lower risk of total knee arthroplasty, especially in patients with high adherence and longer treatment duration. A lower consumption of pain medication was also found for bisphosphonate users among the patients with osteoporosis and osteoarthritis. LEVEL OF EVIDENCE Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

Diabetic hyperglycemia has been suggested to play a role in osteoarthritis. Peroxisome proliferator-activated receptor-γ (PPARγ) was implicated in several pathological conditions including diabetes and inflammation. The detailed effects and mechanisms of hyperglycemia on cartilage damage still need to be clarified. Here, we investigated the role of PPARγ in hyperglycemia-triggered chondrocyte/cartilage damages using a human chondrocyte culture model and a diabetic mouse model. Human chondrocytes were cultured and treated with high concentration of glucose (30 mM) to mimic hyperglycemia in the presence or absence of pioglitazone, a PPARγ agonist. Streptozotocin (STZ) was used to induce mouse diabetes. Our data showed that high glucose induced the protein expressions of cyclooxygenase-2 (COX-2) and production of prostaglandin-E2 (PGE2), interleukin-6 (IL-6), and metalloproteinase-13 (MMP-13), but decreased the protein expression of collagen II and PPARγ in human chondrocytes. These alterations in high glucose-treated human chondrocytes could be reversed by pioglitazone in a dose-dependent manner. Moreover, pioglitazone administration could also significantly reverse the hyperglycemia, formation of AGEs, productions of IL-6 and MMP-13, and cartilage damage in STZ-induced diabetic mice. Taken together, these findings suggest that hyperglycemia down-regulates PPARγ expression and induces inflammatory and catabolic responses in human chondrocytes and diabetic mouse cartilages. © 2014 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 33:???–???, 2015.

Background The benefit of focal treatments, including surgery and radiotherapy, in mSTS patients has not been clear, especially for mSTS patients who had received systemic treatments. Methods Medical records of mSTS patients treated at National Taiwan University Hospital from 2011 to 2017 were collected. The focal tx collected included surgery (either for the primary or metastatic tumors) and radiation therapy (RT). The analysis was limited to patients who had received at least one-line of systemic treatment. Overall survival (OS) was measured from the time of mSTS diagnosis to the date of death or the last follow-up, whichever is later. Results A total of 199 patients, 78 (39%) de novo and 121 (61%) recurrent, mSTS were identified. The median age was 55 (range 20-89) and male to female ratio was 0.86. The most common histologies are leiomyosarcoma (16.5%), liposarcoma (15.6%), and sarcoma NOS (15.6%). Of them, 72 (36.2%) and 48 (24.1%) patients received surgery and RT, respectively. Metastatic STS patients who had received surgical treatment had a significantly better OS as compared with those who did not (median OS 21.9 vs 16.5 months, p = 0.0296). There was a trend that the OS benefit of surgery was mostly in patients with recurrence but not de novo mSTS (p for interaction = 0.08). The type of surgery (primary vs metastatic vs primary + metastatic) did not significantly affect OS (p = 0.608). Patients who received RT had a numerically better survival (median OS 24.4 vs 16.9 months, p = 0.12). In the multivariate Cox model, the OS benefit of surgery remained significant (Table). Table . 407P Adjusted hazard ratio of OS for mSTS patients who received palliative systemic treatment HR 95% CI p-value Female vs male 1.22 (0.85, 1.76) 0.2852 Age 1.01 (1.00, 1.02) 0.0830 Histology Other 1 0.0436 Leiomyosarcoma + Liposarcoma 0.65 (0.43, 0.99) Anthracycline 1.63 (1.12, 2.37) 0.0109 Focal treatment 0.0731 No focal treatment 1 RT 0.62 (0.36, 1.08) 0.0923 Surgery 0.63 (0.40, 0.99) 0.0452 RT + Surgery 0.55 (0.30, 1.00) 0.0502 Conclusions Patients with mSTS had improved OS with focal treatments, especially with surgery. A multi-disciplinary team approach to include the surgeons and radiation oncologists to discuss the optimal treatment of mSTS patients should be advocated. Legal entity responsible for the study The authors. Funding Eli Lilly and Company. Disclosure All authors have declared no conflicts of interest.

Background Elderly STS patients (pts) have different clinicopathological feature and health status compared to younger pts. The optimal management for mSTS remained unclear. Methods From January 2011 to December 2017, mSTS pts in National Taiwan University Hospital and ≥65-years-old at the time of metastatic disease diagnosis were included. The clinicopathological features and the chemotherapy (C/T) received were collected. Results 61 mSTS pts ≥65 y/o were identified; the median age was 74 (range 65- 89); male: female 46%: 54%. The most common histologies were liposarcoma (23%), angiosarcoma (19.7%), and sarcoma NOS (18%). 50 (82%) pts received at least one-line of C/T and the median lines of C/T received was 1 (range 1-5). Anthracycline (exclusive of liposomal doxorubicin (lip-dox)) and ifosfamide were administered to 16 (32%) and 8 (16%) pts; 16 (32%) pts received combination chemotherapy as first-line systemic treatment (tx). Another 9 (18%) and 6 (12%) of patients received lip-dox and oral cyclophosphamide (o-cyclo), as first-line systemic tx. With a median follow-up time of 6.8 months (mos), the median OS was 9.57 mos (95% CI 6.03-22.87 mos); pts who received at least one line of C/T had a numerically but not statistically significant better OS as compared to those who did not receive any C/T (17.50 vs 6.83 mos, p = 0.25). The benefit of systemic C/T were similar for pts aged 65-74 vs ≥ 75 (p for interaction = 0.72). In terms of tx efficacy, the PFS and 1-year OS rate of first-line lip-dox, o-cyclo, and doxorubicin were 7.37 mos and 42%; 16.29 mos and 83%, and 6.97 mos and 40%, respectively. The histologies of mSTS pts who received o-cyclo and lip-dox tx are shown in the table. In multivariate Cox model, only liposarcoma histology had a trend for OS impact (HR 0.4, 95% CI 0.15-1.08, p = 0.07). Table . 410P Histology distribution of pts receiving lip-dox and o-cyclo as first-line therapy Histology Patient no. Oral cyclophosphamide Liposomal doxorubicin Angiosarcoma 12 1 (8.33%) 4 (33.3%) Leiomyosarcoma 7 0 0 Liposarcoma 14 3 (21.43%) 1 (7.12%) Sarcoma NOS 11 0 1 (9.09%) Others 17 2 (11.76%) 3 (17.64%) Conclusions Systemic C/T should be considered for elderly mSTS pts. Less toxic tx such as o-cyclo or lip-dox could be considered for selective histologies. Legal entity responsible for the study The authors. Funding Taiwan Maple Orthopedic Association. Disclosure All authors have declared no conflicts of interest.

This CORR Insights® is a commentary on the article “MicroRNA Regulates Vascular Endothelial Growth Factor Expression in Chondrosarcoma Cells” by Sun and colleagues available at: DOI: 10.1007/s11999-014-3842-0. The author certifies that he, or any member of his immediate family, has no funding or commercial associations (eg, consultancies, stock ownership, equity interest, patent/licensing arrangements, etc) that might pose a conflict of interest in connection with the submitted article. All ICMJE Conflict of Interest Forms for authors and Clinical Orthopaedics and Related Research ® editors and board members are on file with the publication and can be viewed on request. The opinions expressed are those of the writers, and do not reflect the opinion or policy of CORR ® or the Association of Bone and Joint Surgeons®. This CORR Insights ® comment refers to the article available at DOI: 10.1007/s11999-014-3842-0.

Worldwide, acupuncture is a popular alternative medicine for releasing pain, treating diseases, or promoting health. Although it is generally considered safe, a few complications have been reported. These complications ranged from minor side effects, such as pain, local hematoma formation, or the aggravation of symptoms, to serious complications including mechanical injuries, such as pneumothorax and severe infection requiring surgical treatment. In orthopedic clinics, reports of complications caused by acupuncture are rare. We present three cases who developed severe infection following acupuncture, leading to irreversible osteoarthritic changes in their glenohumeral joints. All of them mentioned a history of acupuncture therapy before their shoulder became swollen and hot and no other infection source could be detected. Possible explanations included: (1) breakdown of the sterile technique; (2) no consensus of acupoint or how deep the needle should be inserted; (3) patient’s comorbidities, such as diabetes mellitus or previous shoulder pathology, were not considered. Although these three patients underwent debridement and proper management with antibiotics according to the culture data, eventually, they still progressed to severe glenohumeral joint destruction. Strict infection control guidelines should be established to lower this type of life-threatening complication.

Osteoporosis is recognized as a major public health problem worldwide and in Taiwan. However, many patients with osteoporotic fractures do not receive appropriate assessments or treatments. This guideline, proposed by the Taiwanese Osteoporosis Association, is to serve as a quick reference for healthcare providers to improve the assessment of osteoporosis and development of optimal strategies for osteoporotic management in Taiwan. To review and update osteoporosis management, the guideline is constituted with Taiwan-specific osteoporosis epidemiological data, medication protocols, and the 10-year FRAX(®). The guideline is based on evidence-based medicine and public health considerations. Recommendations are not limited to the reimbursement regulations permitted by the National Health Insurance of Taiwan.

Hip fracture rates in Taiwan are among the highest in the world. The aim of this study was to describe the trends of hip fracture hospitalizations among Taiwanese elderly (aged ≥ 65 years) and the trends of antiosteoporosis medication expenditure from 1999 to 2010. We conducted an ecological study using inpatient health care-utilization data from the Department of Health, and medication expenditure data from the IMS Health, Taiwan. The International Classification of Disease, Clinical Modification, 9th version, code 820 was used to identify hip fracture hospitalizations. Medications included alendronate, calcitonin, ibandronate, raloxifene, strontium ranelate, teriparatide, and zoledronic acid. Year 2010 was assigned as the reference point for age-standardized rates, currency exchange (to the US dollar), and discount rates. Over the 12-year study period, age-standardized hip fracture hospitalizations decreased by 2.7 % annually (p for trend < 0.001) for Taiwanese elders. The decline was more obvious among those aged ≥75 years (6.1 %). However, the number of hip fracture hospitalizations increased from 14,342 to 18,023. Total hospitalization costs increased by US$0.6 ± 0.2 million annually (p for trend = 0.002); however, the per capita costs decreased by US$23.0 ± 8.0 (p for trend = 0.017). The total medication expenditure increased 7.2-fold, from US$8.1 million to US$58.9 million, accounting for an increase in the overall pharmaceutical market by fivefold, from 3.4 to 15.9 ‰ (both p for trend < 0.001). From 1999 to 2010, there was a decline in hip fracture rates among elderly Taiwanese adults with a concomitant increase in antiosteoporosis medication expenditure.

Osteoporosis is characterized by reduced bone mass and quality due to an imbalanced bone remodeling. A grass crop, adlay (Coix lachryma-jobi), is a kind of nourishing food, which has also been used in traditional Chinese medicine. In this study, we investigated the effect of adlay (C. lachryma-jobi L. var. ma-yuen Stapf) on osteoporosis using an ovariectomized mouse model. The adlay diet (10% and 30% adlay in mouse diet) or water extract of adlay (0.3g/kg/day) was given to ovariectomized mice for 4weeks. In some experiments, the primary rat osteoblast cells were used to test the possible mechanism of adlay on osteoporosis. The body weight was slightly increased and uterus weight was markedly decreased in ovariectomized mice, which were not affected by adlay treatment. Adlay diet (30%) and adlay extract feedings significantly reversed the decreased bone alkaline phosphatase activity and calcium contents and bone mineral density in ovariectomized mice. Moreover, adlay extracts increased the osteoblast cell proliferation in a dose-dependent manner. Adlay extracts also increased the protein expressions of proliferating cell nuclear antigen and phosphorylated extracellular signal-regulated kinase (ERK) 1/2 in osteoblast cells. ERK inhibitor PD98059 significantly reversed the increased osteoblast cell proliferation by adlay extracts. Taken together, these findings indicate that adlay effectively alleviates the osteoporotic status in ovariectomized mice. Adlay is capable of increasing the proliferation of osteoblast cells via an ERK-regulated signaling pathway. Adlay may be a helpful healthy food for osteoporosis prevention.

Osteoarthritis (OA) is a degenerative joint disease involving a combination of cartilage degradation and inflammation. EGb761, a standardized extract of Ginkgo biloba leaves, holds an anti-inflammatory potency. Here, we determined whether EGb761 could inhibit lipopolysaccharide (LPS)- and IL-1β-induced inflammatory responses in human articular chondrocytes and apply the chondroprotection in OA rats. We found that LPS markedly induced the productions of PGE2 and NO and the protein expressions of COX-2 and iNOS in human chondrocytes. LPS was also seen to up-regulate the expressions of toll-like receptor-4 (TLR4), its downstream signal TNF receptor-associated factor 6 (TRAF6), and nuclear factor (NF)-κB signaling. These LPS-induced inflammatory responses were efficaciously reversed by EGb761 and its active components quercetin and kampferol. The similar results could be observed by using IL-1β as an in vitro model to mimic an inflammatory response. In an OA rat model, PGE2 and NO levels in blood, the histological alterations, and COX-2 and nitrotyrosine expressions in cartilages were markedly increased, which were effectively reversed by EGb761. Our results suggested that EGb761 exerts the anti-inflammatory effects on human articular chondrocytes and OA rats.

Oncostatin M (OSM) belongs to IL-6 subfamily and is mostly produced by T lymphocytes. High levels of OSM are detected in the pannus of rheumatoid arthritis (RA) patients and it may arouse the inflammation responses in joints and eventually leads to bone erosion. Placenta growth factor (PLGF) is an angiogenic factor and highly homologous with vascular endothelial growth factor (VEGF). It has been recently reported that PLGF is highly expressed in synovial tissue and enhances the production of proinflammatory cytokines including TNF-α and IL-6. Here, we demonstrated that OSM increased mRNA and protein levels of PLGF in a time- and concentration-dependent manner in RA synovial fibroblasts. Inhibitors of JAK3 and PI3K antagonized OSM-induced production of PLGF. OSM enhanced the phosphorylation of Tyr705-STAT3, Ser727-STAT3, Ser473-Akt, and increased the nuclear translocation of phosphorylated STAT3 time-dependently. Transfection of dominant negative Akt or application of PI3K inhibitorLY294002 significantly inhibited p-Tyr705-STAT3, p-Ser727-STAT3, and PLGF expression, indicating that Akt is involved in JAK3/STAT3/PLGF signaling cascade. To further examine whether STAT3 binds to the promoter region of PLGF, Chip assay was used and it was found that OSM could bind with PLGF promoter, which was inhibited by JAK3 and PI3K inhibitors. Accumulation of PLGF in the pannus may contribute to the inflammation, angiogenesis and joints destruction in RA patients. These findings demonstrated the important role of OSM in the pathology network of RA and provided novel therapeutic drug targets for RA treatment.

Background: The suprascapular nerve accounts for 70% of shoulder sensory innervations, and suprascapular nerve block (SSNB) has been shown to be effective in the relief of chronic shoulder pain including rotator cuff tendinitis, subdeltoid impingement syndrome, and adhesive capsulitis. However, this remains inconclusive for patients undergoing surgery. The present meta-analysis aimed to explore the effectiveness of SSNB for relieving acute postoperative shoulder pain. Objective: To explore the effectiveness of SSNB for relieving acute post-operative shoulder pain. Study Design: A systematic review and meta-analysis. Setting: Services of general surgery, orthopaedics, and anaesthesiology. Methods: A systematic search of studies on SSNB for post-operative shoulder pain was conducted mainly in PubMed and Scopus. The standardized mean difference (SMD) of postoperative pain scales of SSNB versus placebo was treated as the primary outcome, whereas the odds ratio of nausea of SSNB versus placebo comprised the secondary outcome. Results: The meta-analysis included 7 randomized controlled trials and 2 comparative studies comprising 681 participants in total. The quantitative analysis showed a significantly lower pain level of SSNB versus placebo in the shoulder surgery patient group (SMD: -0.33; 95% confidence level [CI]: -0.51 to -0.15), but not in the non-shoulder surgery group (SMD: 0.28; 95% CI: -0.37 to 1.93). The pooled odds ratio of nausea in the SSNB arm compared with the placebo arm was 0.20 (95% CI: 0.09 to 0.45), indicating a reduction in the incidence of nausea following SSNB. Limitations: Heterogeneity of included trials. Conclusions: SSNB significantly reduced acute post-operative shoulder pain in the shoulder surgery group but not in patients undergoing laparoscopic surgery or thoracotomy. This suggests that SSNB can be used as a method of polymodal analgesia for patients undergoing shoulder surgery; however, it is not recommended for the non-shoulder surgery patient population. Key words: Suprascapular nerve, shoulder surgery, thoracotomy, laparoscopic surgery

There is no gold standard in diagnosing sarcopenia. We aimed to assess the validity of screening sarcopenia using SARC-F (sluggishness, assistance in walking, rise from a chair, climb stairs, falls).Prospective cohort study.Community hospital in Taiwan.Community-dwelling senior citizens.Participants were interviewed with a structured questionnaire annually. The questionnaire items were recoded into the 5 items of SARC-F (sluggishness, assistance in walking, rise from a chair, climb stairs, falls). In the baseline year, a subgroup was tested for grip strength and body composition. Healthcare utilization and mortality were based on self-report and hospital records. Our main outcome was 4-year mortality. Secondary outcomes included hospitalization, emergency care use, and quality of life (QOL) measured using the CASP-12 scale (control, autonomy, self-realization, pleasure (control, autonomy, self-realization, pressure).There were 670 participants. The mean age was 76.1 (standard deviation 6.36). One-half were men (n = 340, 50.7%). The prevalence of sarcopenia was 6.1% (n = 41). SARC-F scores were inversely associated with grip strength (P = .001) and skeletal muscle composition (P = .045). Participants with sarcopenia were mostly women (P = .005) and older (P .001). In univariate analysis, sarcopenia was associated with 1- to 4-year mortalities (P = .033, .001, .001,.001, respectively), overall hospitalization (P = .004), overall emergency care use (P = .017), and QOL (P .001). In multivariate model, sarcopenia [odds ratio (OR) 7.35, 95% confidence interval (CI) 2.67-20.18], age (OR 1.19, 95% CI 1.09-1.29 for each year), and taking vitamin D supplements (OR 0.29, 95% CI 0.11-0.74) were factors associated with mortality.Sarcopenia screened using SARC-F was associated with subsequent QOL, overall hospitalization, overall emergency care use, and 4-year mortality. SARC-F can serve as a quick screening tool of sarcopenia.

// Siao-Syun Guan 1,2,* , Meei-Ling Sheu 3,* , Rong-Sen Yang 4,* , Ding-Cheng Chan 5,* , Cheng-Tien Wu 1 , Ting-Hua Yang 6 , Chih-Kang Chiang 1,7 and Shing-Hwa Liu 1,8,9 1 Institute of Toxicology, College of Medicine, National Taiwan University, Taipei, Taiwan 2 Institute of Nuclear Energy Research, Atomic Energy Council, Executive Yuan, Taoyuan, Taiwan 3 Biomedical Sciences, College of Life Sciences, National Chung Hsing University, Taichung, Taiwan 4 Department of Orthopaedics, College of Medicine, National Taiwan University, Taipei, Taiwan 5 Department of Geriatrics and Gerontology, College of Medicine, National Taiwan University, Taipei, Taiwan 6 Department of Otolaryngology, National Taiwan University Hospital, Taipei, Taiwan 7 Department of Integrated Diagnostics and Therapeutics and Internal Medicine, College of Medicine and Hospital, National Taiwan University, Taipei, Taiwan 8 Department of Medical Research, China Medical University Hospital, China Medical University, Taichung, Taiwan 9 Department of Pediatrics, National Taiwan University Hospital, Taipei, Taiwan * These authors have contributed equally to this work Correspondence to: Shing-Hwa Liu, email: // Chih-Kang Chiang, email: // Keywords : diabetes, advanced glycation end products, β-cell hypertrophy, heat shock protein 60, Pathology Section Received : March 16, 2016 Accepted : March 29, 2016 Published : April 05, 2016 Abstract Heat shock protein 60 (HSP60) is a mitochondrial chaperone. Advanced glycation end products (AGEs) have been shown to interfere with the β-cell function. We hypothesized that AGEs induced β-cell hypertrophy and dysfunction through a HSP60 dysregulation pathway during the stage of islet/β-cell hypertrophy of type-2-diabetes. We investigated the role of HSP60 in AGEs-induced β-cell hypertrophy and dysfunction using the models of diabetic mice and cultured β-cells. Hypertrophy, increased levels of p27 Kip1 , AGEs, and receptor for AGEs (RAGE), and decreased levels of HSP60, insulin, and ATP content were obviously observed in pancreatic islets of 12-week-old db/db diabetic mice. Low-concentration AGEs significantly induced the cell hypertrophy, increased the p27 Kip1 expression, and decreased the HSP60 expression, insulin secretion, and ATP content in cultured β-cells, which could be reversed by RAGE neutralizing antibody. HSP60 overexpression significantly reversed AGEs-induced hypertrophy, dysfunction, and ATP reduction in β-cells. Oxidative stress was also involved in the AGEs-decreased HSP60 expression in β-cells. Pancreatic sections from diabetic patient showed islet hypertrophy, increased AGEs level, and decreased HSP60 level as compared with normal subject. These findings highlight a novel mechanism by which a HSP60-correlated signaling pathway contributes to the AGEs-RAGE axis-induced β-cell hypertrophy and dysfunction under diabetic hyperglycemia.