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Objectives: This study aimed to present the Asia-Pacific consensus on long-term and sequential therapy for osteoporosis, offering evidence-based recommendations for the effective management of this chronic condition. The primary focus is on achieving optimal fracture prevention through a comprehensive, individualized approach. Methods: A panel of experts convened to develop consensus statements by synthesizing the current literature and leveraging clinical expertise. The review encompassed long-term anti-osteoporosis medication goals, first-line treatments for individuals at very high fracture risk, and the strategic integration of anabolic and antiresorptive agents in sequential therapy approaches. Results: The panelists reached a consensus on 12 statements. Key recommendations included advocating for anabolic agents as the first-line treatment for individuals at very high fracture risk and transitioning to antiresorptive agents following the completion of anabolic therapy. Anabolic therapy remains an option for individuals experiencing new fractures or persistent high fracture risk despite antiresorptive treatment. In cases of inadequate response, the consensus recommended considering a switch to more potent medications. The consensus also addressed the management of medication-related complications, proposing alternatives instead of discontinuation of treatment. Conclusions: This consensus provides a comprehensive, cost-effective strategy for fracture prevention with an emphasis on shared decision-making and the incorporation of country-specific case management systems, such as fracture liaison services. It serves as a valuable guide for healthcare professionals in the Asia-Pacific region, contributing to the ongoing evolution of osteoporosis management.

Background: A fracture liaison services (FLSs) and its modified services reduce refractures and mortality and can be cost-effective. Limited studies have addressed whether urban–rural differences exist in vertebral fracture outcomes and management. Therefore, the aims of the study were to investigate any urban–rural differences in refracture, mortality, prescription pattern, and associated factors of vertebral fractures after receiving assistance from an FLSs. Methods: Baseline characteristics and osteoporosis medication prescription patterns of participants were collected. After 1-year follow-up, mortality, refracture rate, and osteoporosis medication switching and adherence were evaluated. Multivariate logistic regressions were performed to identify baseline correlates on one-year mortality. Results: There was higher mortality rate in the rural group but no urban–rural difference in the 1-year refracture rate after implementation of FLSs and medication management services (MMSs). The types of osteoporosis medications prescribed for both groups were similar, but participants in the rural group were less likely to change their osteoporosis medications during the 1-year follow-up timeframe and with lower adherence rate. The likelihood of being older and having chronic kidney disease, osteoarthritis, and neurological disease was higher in the rural group. Conclusion: Our multicomponent services have similar effectiveness in osteoporosis treatment between urban and rural areas. The overall adherence rate was lower in the rural group with higher mortality but no difference in the refracture rate in one year.

Abstract Background Survival is an important factor to consider when clinicians make treatment decisions for patients with skeletal metastasis. Several preoperative scoring systems (PSSs) have been developed to aid in survival prediction. Although we previously validated the Skeletal Oncology Research Group Machine‐learning Algorithm (SORG‐MLA) in Taiwanese patients of Han Chinese descent, the performance of other existing PSSs remains largely unknown outside their respective development cohorts. We aim to determine which PSS performs best in this unique population and provide a direct comparison between these models. Methods We retrospectively included 356 patients undergoing surgical treatment for extremity metastasis at a tertiary center in Taiwan to validate and compare eight PSSs. Discrimination (c‐index), decision curve (DCA), calibration (ratio of observed:expected survivors), and overall performance (Brier score) analyses were conducted to evaluate these models’ performance in our cohort. Results The discriminatory ability of all PSSs declined in our Taiwanese cohort compared with their Western validations. SORG‐MLA is the only PSS that still demonstrated excellent discrimination (c‐indexes>0.8) in our patients. SORG‐MLA also brought the most net benefit across a wide range of risk probabilities on DCA with its 3‐month and 12‐month survival predictions. Conclusions Clinicians should consider potential ethnogeographic variations of a PSS's performance when applying it onto their specific patient populations. Further international validation studies are needed to ensure that existing PSSs are generalizable and can be integrated into the shared treatment decision‐making process. As cancer treatment keeps advancing, researchers developing a new prediction model or refining an existing one could potentially improve their algorithm's performance by using data gathered from more recent patients that are reflective of the current state of cancer care.

Abstract Background Organotin pollutant tributyltin (TBT) is an environmental endocrine disrupting chemical and is a known obesogen and diabetogen. TBT can be detected in human following consumption of contaminated seafood or water. The decrease in muscle strength and quality has been shown to be associated with type 2 diabetes in older adults. However, the adverse effects of TBT on the muscle mass and function still remain unclear. Here, we investigated the effects and molecule mechanisms of low‐dose TBT on skeletal muscle regeneration and atrophy/wasting using the cultured skeletal muscle cell and adult mouse models. Methods The mouse myoblasts (C2C12) and differentiated myotubes were used to assess the in vitro effects of low‐dose tributyltin (0.01–0.5 μM). The in vivo effects of TBT at the doses of 5 and 25 μg/kg/day (n = 6/group), which were five times lower than the established no observed adverse effect level (NOAEL) and equal to NOAEL, respectively, by oral administration for 4 weeks on muscle wasting and muscle regeneration were evaluated in a mouse model with or without glycerol‐induced muscle injury/regeneration. Results TBT reduced myogenic differentiation in myoblasts (myotube with 6–10 nuclei: 53.9 and 35.8% control for 0.05 and 0.1 μM, respectively, n = 4, P 0.05 and P 0.05 and P 0.05 and P

BackgroundSince 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. MethodsBy 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. ResultsOur 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. ConclusionThe 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.

Osteoporosis greatly increases the risk of fractures. Osteoporotic fractures negatively impact quality of life, increase the burden of care, and increase mortality. Taiwan is an area with a high prevalence of osteoporosis. This updated summary of guidelines has been developed by experts of the Taiwan Osteoporosis Association with the intention of reducing the risks of osteoporotic fractures and improving the quality of care for patients with osteoporosis. The updated guidelines compile the latest evidence to provide clinicians and other healthcare professionals with practical recommendations for the prevention, diagnosis, and management of osteoporosis under clinical settings in Taiwan.

Background: Previous epidemiological researchers have used various algorithms to identify a second hip fracture; however, there has been no validation of these algorithms to date. This study aimed to verify existing algorithms for identifying second hip fracture under the International Classification of Diseases diagnostic coding systems. Furthermore, we examined the validity of two newly proposed algorithms that integrated the concept of periprosthetic fractures and laterality of the ICD-10 coding system. Methods: Claims data of patients hospitalized for hip fracture from National Taiwan University Hospitals between 2007 and 2020 were retrieved. Hip fracture was confirmed by 2 orthopaedic surgeons with medical records and imaging data as gold standards. The validity of 9 existing and 2 newly proposed algorithms for identifying second hip fracture was evaluated. Results: The positive predictive value (PPV) range between 84% and 90% in existing algorithms for identifying second hip fractures. Noteworthy, the longer time interval for discrimination resulted in slightly increased PPV (from 87% to 90%), while decreased sensitivity noticeably (from 87% to 72%). When considering the information about periprosthetic fracture, the PPV increased to 91% without diminished sensitivity. The PPV of the newly proposed ICD-10-specific algorithm was 100%. Conclusion: Algorithms integrated clinical insights of periprosthetic fractures and laterality concept of ICD-10 coding system provided satisfactory validity and help precisely define second hip fracture in future database research.

Background: Adherence to anti-osteoporosis medications (AOMs) is crucial. National Health Insurance (NHI) in Taiwan has its own rules of reimbursement rule for AOMs. The midterm adherence remained inconclusive. Here we investigated the adherence according to the initially used AOMs, for three consecutive years. Methods: The nationwide cohort study from 2008 to 2018, based on Taiwan's National Health Insurance Research Database, included 336,229 patients. Their adherence, indicated by medication possession ratio (MPR), to the initial AOMs was investigated yearly for three consecutive years. The overall MPRs (OMPR), including the switched AOMs, were also calculated in the first year. The Sankey diagram further visualized the patient flows toward different adherence according to the initial AOMs. Results: The OMPR in the first year improved if the patients used AOMs with longer dosing intervals. 100%, 68.9%, 40.7%, and 34.0% of the patients started the treatment with zoledronate, denosumab, alendronate, and raloxifene, respectively, had OMPR ≥75% in the first year. In the 3rd year, only 20.89%, 24.13%, and 12.83% of the patients continuously treated with zoledronate, denosumab, and alendronate, respectively, had MPR ≥75%. From the Sankey diagram, we also observed that patients who had poor adherence at one year were inclined to have poor adherence or discontinue antiosteoporosis treatment in the next year. Conclusion: The initial AOMs and the observed adherence may provide clues for optimizing patient treatment. The real-world adherence in Taiwan was far from satisfactory in our study.

Postmenopausal women are at significant risk for osteoporotic fractures due to their rapid bone loss. Half of all postmenopausal women will get an osteoporosis-related fracture over their lifetime, with 25% developing a spine deformity and 15% developing a hip fracture. By 2050, more than half of all osteoporotic fractures will occur in Asia, with postmenopausal women being the most susceptible. Early management can halt or even reverse the progression of osteoporosis. Consequently, on October 31, 2020, the Taiwanese Osteoporosis Association hosted the Asia–Pacific (AP) Postmenopausal Osteoporotic Fracture Prevention (POFP) consensus meeting, which was supported by the Asian Federation of Osteoporosis Societies (AFOS) and the Asia Pacific Osteoporosis Foundation (APOF). International and domestic experts developed ten applicable statements for the prevention of osteoporotic fractures in postmenopausal women with low bone mass or osteoporosis but no fragility fractures in the AP region. The experts advocated, for example, that postmenopausal women with a high fracture risk be reimbursed for pharmaceutical therapy to prevent osteoporotic fractures. More clinical experience and data are required to modify intervention tactics.

Background: Osteoporosis is a common metabolic bone disease that benefits from many newly developed anti-osteoporosis medications (AOMs). Reimbursement policies need to allocate medical budgets properly based on evidence-based data. This study aimed to investigate the 11-year secular trend, focusing on older age and males in this adjustment wave of the National Health Insurance reimbursement. Methods: We adopted a nationwide cohort from Taiwan's National Health Insurance Research Database (NHIRD). Patients undergoing newly initiated AOMs from 2008 to 2018 were included. The AOMs in this study included denosumab, zoledronate, ibandronate, alendronate, raloxifene, and risedronate. Patients

Background: The objective of this research was to report the trend of osteoporosis care after hip fractures from usual care (UC) and to compare the quality of care with those who received fracture liaison services (FLSs). Methods: Data on osteoporosis care for patients with hip fracture were acquired from the National Health Insurance claims (UC group), and surveys from FLS programs (FLS group). A total of 183,300 patients receiving UC and 3010 patients receiving FLS were studied. For the two groups, common osteoporosis care indicators, such as bone mineral density (BMD) testing rate, antiosteoporosis medication commencement rate, and adherence rate were described. Results: There were 2488 participants (82.7%) in the FLS group who completed Dual-energy X-ray absorptiometry (DXA) in 8 weeks, 155 (5.1%) who finished it between 8 weeks and 1 year. Even in 2018, when the DXA completion rate was at its highest, the completion rate in the UC group was only 23.5%. In terms of medication commencement, 2372 FLS patients (78.8%) received treatment within 3 months. Only 24.9% of the UC patients received antiosteoporosis medication within 3 months. Furthermore, antiosteoporosis medication adherence rate was 92.2% after 1 year and 83.9% after 2 years in the FLS group, but these were only 66.5% and 42.7%, respectively, in the UC group. Conclusion: Patients who received FLS had more timely BMD exams, antiosteoporosis medication treatment, and higher adherence to antiosteoporosis therapy than those who received UC. The discrepancy in rates of continuing treatment became more significant over time between both groups.

Background: The Bureau of National Health Insurance in Taiwan implemented a new reimbursement scheme incorporating bone mineral density (BMD) criteria on Jan. 1, 2011. This study aimed to investigate a real-life 11-year secular trend of adherence in new AOMs users and evaluated the change of adherence to AOMs therapy in different urbanization areas after reimbursement criteria were restrained. Methods: We used Taiwan's National Health Insurance Research Database to identify new AOMs users as our study population. The AOMs in this study included denosumab, zoledronate, ibandronate, alendronate, raloxifene, and risedronate. The first prescription date of AOMs was defined as the cohort entry date. The adherence rates within one year after initiation were assessed. Results: High adherence (≥75%) in the first year increased markedly after the new reimbursement scheme in 2011, changing from 31.8% in 2008, and 41.7% in 2011 to 54.2% in 2018. On the other hand, low adherence (

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 and purpose: Predicted survival may influence the treatment decision for patients with skeletal extremity metastasis, and PATHFx was designed to predict the likelihood of a patient dying in the next 24 months. However, the performance of prediction models could have ethnogeographical variations. We asked if PATHFx generalized well to our Taiwanese cohort consisting of 356 surgically treated patients with extremity metastasis. Patients and methods: We included 356 patients who underwent surgery for skeletal extremity metastasis in a tertiary center in Taiwan between 2014 and 2019 to validate PATHFx’s survival predictions at 6 different time points. Model performance was assessed by concordance index (c-index), calibration analysis, decision curve analysis (DCA), Brier score, and model consistency (MC). Results: The c-indexes for the 1-, 3-, 6-, 12-, 18-, and 24-month survival estimations were 0.71, 0.66, 0.65, 0.69, 0.68, and 0.67, respectively. The calibration analysis demonstrated positive calibration intercepts for survival predictions at all 6 timepoints, indicating PATHFx tended to underestimate the actual survival. The Brier scores for the 6 models were all less than their respective null model’s. DCA demonstrated that only the 6-, 12-, 18-, and 24-month predictions appeared useful for clinical decision-making across a wide range of threshold probabilities. The MC was < 0.9 when the 6- and 12-month models were compared with the 12-month and 18-month models, respectively. Interpretation: In this Asian cohort, PATHFx’s performance was not as encouraging as those of prior validation studies. Clinicians should be cognizant of the potential decline in validity of any tools designed using data outside their particular patient population. Developers of survival prediction tools such as PATHFx might refine their algorithms using data from diverse, contemporary patients that is more reflective of the world’s population.

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.

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.

The relationship between plasticizer di(2-ethylhexyl) phthalate (DEHP) and low birth weight in neonates has been reported. Immature muscle differentiation may be involved in low birth weight. The myotoxic characteristics of chemicals have been observed in differentiating immortalized and primary muscle cells. Here, we explored the myotoxic effects of DEHP and its metabolite mono(2-ethylhexyl) phthalate (MEHP) in vitro using the immortalized mouse skeletal myoblasts C2C12 and primary human skeletal muscle progenitor cell (HSMPC) models. We found that both DEHP and MEHP at the concentrations of 10–100 μM, which were non- and low-cytotoxicity concentrations, significantly and dose-dependently inhibited the creatine kinase activity, myotube formation with multiple nuclei, and myogenin and myosin heavy chain (muscle differentiation markers) protein expression in C2C12 and HSMPCs under differentiation medium. Both DEHP and MEHP significantly decreased Akt phosphorylation in C2C12 and HSMPCs during differentiation. Taken together, DEHP and its metabolite MEHP are capable of inhibiting Akt-regulated myogenesis in myoblasts/myogenic progenitors during differentiation. These findings suggest the possibility of DEHP as an environmental risk factor affecting skeletal myogenic differentiation. Moreover, these in vitro muscle cell models may be a possible alternative method to animal myotoxicity testing.

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

Abstract Background Acrolein is an extremely electrophilic aldehyde. Increased urinary acrolein adducts have been found in type 2 diabetic patients and people with a smoking habit. The increased blood acrolein was shown in patients who received the cancer drug cyclophosphamide. Both diabetes and smoking are risk factors for skeletal muscle wasting or atrophy. Acrolein has been found to induce myotube atrophy in vitro. The in vitro and in vivo effects and mechanisms of acrolein on myogenesis and the in vivo effect of acrolein on muscle wasting still remain unclear. Methods C2C12 myoblasts were used to assess the effects of low‐dose acrolein (0.125–1 μM) on myogenesis in vitro. Mice were exposed daily to acrolein in distilled water by oral administration (2.5 and 5 mg/kg) for 4 weeks with or without glycerol‐induced muscle injury to investigate the effects of acrolein on muscle wasting and regeneration. Results Non‐cytotoxic‐concentration acrolein dose dependently inhibited myogenic differentiation in myoblasts (myotube formation inhibition: 0.5 and 1 μM, 66.25% and 46.25% control, respectively, n = 4, P

Summary: Objective: Femoral neck shortening is a common complication after surgical treatment for intracapsular femoral neck fractures. This study investigated whether fully-threaded Headless Compression Screw (FTHCS) can be a more length-stable implant than partially-threaded cannulated screw (PTCS) in reducing femoral neck shortening. Methods: A total of 50 patients with undisplaced femoral neck fractures (17 treated by internal fixation with three FTHCS, and 33 treated by three PTCS) from 2011 to 2014 were enrolled in this study. The radiography of the hips and medical records were reviewed for proximal femur geometry and complications. Results: Significant shortening of the femoral neck length until union were noted in both group (FTHCS group: −2.5 mm, p = 0.045; PTCS group: −2.4 mm, p = 0.011). There was no significant difference in the length of femoral neck shortening between groups (p = 0.855). Age was the only significant risk factor for >5 mm of femoral neck shortening (p = 0.041). The femoral neck-shaft angle tended to reduce and become more varus in both groups (FTHCS: −2.7°, SD = 4.5, p = 0.028; PTCS: −5.0°, SD = 8.3, p = 0.002), but the differences between groups were nonsignificant (p = 0.577). The complication rates were similar between FTHCS and PTCS (17.6% and 21.2%, p > 0.999). Conclusion: The FTHCSs may be a substitute for PTCSs, but it cannot prevent femoral neck shortening and varus collapse after fracture fixation. Future studies should focus on how to preserve femoral neck length and hip function after femoral neck fractures. Keywords: Cannulated screw, Femoral neck shortening, Femoral neck fractures, Headless compression screw, Thread

BackgroundIdentification of vertebral fractures (VFs) is critical for effective secondary fracture prevention owing to their association with the increasing risks of future fractures. Plain abdominal frontal radiographs (PARs) are a common investigation method performed for a variety of clinical indications and provide an ideal platform for the opportunistic identification of VF. This study uses a deep convolutional neural network (DCNN) to identify the feasibility for the screening, detection, and localization of VFs using PARs.MethodsA DCNN was pretrained using ImageNet and retrained with 1306 images from the PARs database obtained between August 2015 and December 2018. The accuracy, sensitivity, specificity, and area under the receiver operating characteristic curve (AUC) were evaluated. The visualization algorithm gradient-weighted class activation mapping (Grad-CAM) was used for model interpretation.ResultsOnly 46.6% (204/438) of the VFs were diagnosed in the original PARs reports. The algorithm achieved 73.59% accuracy, 73.81% sensitivity, 73.02% specificity, and an AUC of 0.72 in the VF identification.ConclusionComputer driven solutions integrated with the DCNN have the potential to identify VFs with good accuracy when used opportunistically on PARs taken for a variety of clinical purposes. The proposed model can help clinicians become more efficient and economical in the current clinical pathway of fragile fracture treatment.

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.

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

Osteoporosis and its associated fragility fractures are becoming a severe burden in the healthcare system globally. In the Asian-Pacific (AP) region, the rapidly increasing in aging population is the main reason accounting for the burden. Moreover, the paucity of quality care for osteoporosis continues to be an ongoing challenge. The Fracture Liaison Service (FLS) is a program promoted by International Osteoporosis Foundation (IOF) with a goal to improve quality of postfracture care and prevention of secondary fractures. In this review article, we would like to introduce the Taiwan FLS network. The first 2 programs were initiated in 2014 at the National Taiwan University Hospital and its affiliated Bei-Hu branch. Since then, the Taiwan FLS program has continued to grow exponentially. Through FLS workshops promoted by the Taiwanese Osteoporosis Association (TOA), program mentors have been able to share their valuable knowledge and clinical experience in order to promote establishments of additional programs. With 22 FLS sites including 11 successfully accredited on the best practice map, Taiwan remains as one of the highest FLS coverage countries in the AP region, and was also granted the IOF Best Secondary Fracture Prevention Promotion award in 2017. Despite challenges faced by the TOA, we strive to promote more FLS sites in Taiwan with a main goal of ameliorating further health burden in managing osteoporotic patients. Keywords: Asia-Pacific region, Taiwan, Fracture Liaison Service, Best Practice Framework, Osteoporosis

Abstract 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.

Abstract 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.

Abstract 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.

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.

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 >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.

Abstract 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 Taiwanese FRAX® calculator was launched in 2010. However, cost-effectiveness thresholds for the prescription of antiosteoporosis medications were not established. This study aims to establish and evaluate FRAX®-based probability thresholds in Taiwan. Methods: Using previous data from Taiwan and literature, we determined cost-effectiveness thresholds for prevention of osteoporotic fractures by alendronate with a Markov model, as well as using two other translational approaches. Sensitivity analysis was applied using different alendronate prices. A clinical sample was used to test these Taiwan-specific thresholds by determining the percentages of high-risk patients who would be qualified for current National Health Insurance reimbursement. Results: With the Markov model, the intervention threshold for hip fracture was 7% for women and 6% for men; for major osteoporotic fracture, it was 15% for women and 12.5% for men. Both translational approach models were cost effective only for certain age groups. However, if branded alendronate was reimbursed at 60% of the current price, they became cost effective in almost all age groups. This clinical screening study showed that the National Health Insurance Administration model identified the highest proportion (44%) of patients qualified for National Health Insurance reimbursements, followed by the Markov model (30%), and the United States model (22%). Conclusion: Three FRAX®-based models of alendronate use were established in Taiwan to help optimize treatment strategies. The government is encouraged to incorporate FRAX®-based approaches into the reimbursement policy for antiosteoporosis medicines.

Osteoporosis is the second most common disease only secondary to cardiovascular disease, with the risk of fracture increasing with age. Osteoporosis is caused by an imbalance between osteoblastogenesis and osteoclastogenesis processes. Osteoclastogenesis may be enhanced, osteoblastogenesis may be reduced, or both may be evident. Inflammation and high reactive oxygen enhance osteoclastogenesis while reducing osteoblastogenesis by inducing osteoblast apoptosis and suppressing osteoblastic proliferation and differentiation. Catechins, the main polyphenols found in green tea with potent anti-oxidant and anti-inflammatory properties, can counteract the deleterious effects of the imbalance of osteoblastogenesis and osteoclastogenesis caused by osteoporosis. Green tea catechins can attenuate osteoclastogenesis by enhancing apoptosis of osteoclasts, hampering osteoclastogenesis, and prohibiting bone resorption in vitro. Catechin effects can be directly exerted on pre-osteoclasts/osteoclasts or indirectly exerted via the modulation of mesenchymal stem cells (MSCs)/stromal cell regulation of pre-osteoclasts through activation of the nuclear factor kB (RANK)/RANK ligand (RANKL)/osteoprotegerin (OPG) system. Catechins also can enhance osteoblastogenesis by enhancing osteogenic differentiation of MSCs and increasing osteoblastic survival, proliferation, differentiation, and mineralization. The in vitro effects of catechins on osteogenesis have been confirmed in several animal models, as well as in epidemiological observational studies on human subjects. Even though randomized control trials have not shown that catechins provide anti-fracture efficacy, safety data in the trials are promising. A large-scale, placebo-controlled, long-term randomized trial with a tea regimen intervention of optimal duration is required to determine anti-fracture efficacy.

Osteoarthritis and sarcopenia are two major joint and skeletal muscle diseases prevalent during aging. Osteoarthritis is a multifactorial progressive degenerative and inflammatory disorder of articular cartilage. Cartilage protection and pain management are the two most important strategies in the management of osteoarthritis. Sarcopenia, a condition of loss of muscle mass and strength, is associated with impaired neuromuscular innervation, the transition of skeletal muscle fiber type, and reduced muscle regenerative capacity. Management of sarcopenia requires addressing both skeletal muscle quantity and quality. Emerging evidence suggests that green tea catechins play an important role in maintaining healthy joints and skeletal muscle. This review covers (i) the prevalence and etiology of osteoarthritis and sarcopenia, such as excessive inflammation and oxidative stress, mitochondrial dysfunction, and reduced autophagy; (ii) the effects of green tea catechins on joint health by downregulating inflammatory signaling mediators, upregulating anabolic mediators, and modulating miRNAs expression, resulting in reduced chondrocyte death, collagen degradation, and cartilage protection; (iii) the effects of green tea catechins on skeletal muscle health via maintaining a dynamic balance between protein synthesis and degradation and boosting the synthesis of mitochondrial energy metabolism, resulting in favorable muscle homeostasis and mitigation of muscle atrophy with aging; and (iv) the current study limitations and future research directions.

Objective: To compare the osteoporosis awareness and its association with 10-year fracture risks between young and old breast cancer survivors. Methods: During the 2011 Pink October campaign hosted by the Taiwan Breast Cancer Alliance and the Taiwanese Osteoporosis Association, questionnaires on osteoporosis awareness and FRAX variables were distributed. Data from participants aged 40 years and older (n = 807) were analyzed. Comparisons were made between those aged below and above 50 years, and among different tertiles of predicted fracture risk groups. Results: Mean age was 56.0 ± 7.7 years. Only half (52.7%) showed a high level of osteoporosis awareness. Older survivors were more likely to exhibit higher awareness levels (55.0% vs. 44.8%; p

Hemorrhagic cystitis is a common complication with chemotherapeutic alkylating agents. We investigated the possible prognostic factors of cyclophosphamide-induced hemorrhagic cystitis in children. Methods: Medical records of children (< 18 years old) with cyclophosphamide-related hemorrhagic cystitis were collected retrospectively from January 2000 to December 2010 in a tertiary care center. We also prospectively enrolled children (< 18 years old) with cyclophosphamide treatment. Results: The retrospective study consisted of 23 patients whose median age was 11 years. The median day of onset time was 1 day after cyclophosphamide usage. The hemato-oncological diseases included acute leukemia (39.1%), lymphoma (13%), blastoma (13%), sarcoma (13%), aplastic anemia (13%), and others (8.7%). Patients who received bone marrow transplantation (BMT) had significantly longer duration of hemorrhagic cystitis than those who did not receive BMT (p