Asia-Pacific consensus on long-term and sequential therapy for osteoporosis.

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.

Epidemiology and clinical impact of osteoporosis in Taiwan: A 12-year trend of a nationwide population-based study.

BACKGROUND: Osteoporosis increases the fracture and mortality risk of patients and has a higher disease burden than some cancers. Therefore, global concerns regarding the prevention and treatment of osteoporosis have been raised. However, fast-aging Taiwan lacks national epidemiological data on osteoporosis in recent years. We aimed to establish and update epidemiological data on osteoporosis by analyzing national data from 2008 to 2019. METHODS: We estimated the prevalence and incidence of osteoporosis in patients aged ≥50 years based on claims data from Taiwan's National Health Insurance database from 2008 to 2019. We also analyzed the key parameters of fracture care (anti-osteoporosis medication use, bone mineral density examination rate, and length of hospital stay) to understand the secular trend of management and related clinical outcomes (imminent refracture rate and mortality). RESULTS: The number of prevalent osteoporosis increased from 2008 to 2015 and remained constant until 2019; however, the age-standardized prevalence and incidence rates declined from 2008 to 2019 (3.77%-2.91% and 2.08%-1.02%, respectively). The overall incidence rates of hip and spine fractures decreased significantly by 34% and 27%, respectively. For patients with hip and spine fractures, the immanent refracture rates were 8.5% and 12.9% and the 1-year mortality rate remained stable at approximately 15% and 6%, respectively. CONCLUSION: The age-standardized prevalence and incidence rates decreased remarkably from 2008 to 2019, while the number of prevalent osteoporosis remained steady. Patients with hip fractures encountered a high 1-year mortality rate, while the risk of imminent refracture was notable for patients with spine fractures.

Asia-pacific consensus on osteoporotic fracture prevention in postmenopausal women with low bone mass or osteoporosis but no fragility fractures.

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.

Consensus Statement on the Use of Bone Turnover Markers for Short-Term Monitoring of Osteoporosis Treatment in the Asia-Pacific Region.

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.

Pharmacologic intervention for prevention of fractures in osteopenic and osteoporotic postmenopausal women: Systemic review and meta-analysis.

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.

Iron Overload Associated Endocrine Dysfunction Leading to Lower Bone Mineral Density in Thalassemia Major.

CONTEXT: Patients with thalassemia major (TM) have a lower bone mineral density (BMD) and higher risk of fracture than the general population. The possible mechanisms include anemia, iron overload, malnutrition, and hormonal deficiency, but these have not been thoroughly investigated. OBJECTIVE: To identify major mineral and hormonal factors related to BMD in adult TM patients to provide human evidence for the proposed mechanisms. DESIGN: Retrospective study. SETTING: Referral center. PATIENTS: Twenty-nine patients with ß-TM, aged 23 to 44 years who were followed-up during 2017 to 2018 were enrolled. OUTCOME MEASUREMENTS: Endocrine profiles, including thyroid, parathyroid, and pituitary function, glucose, vitamin D, calcium, phosphate, and fibroblast growth factor 23 (FGF23) were obtained. The relationships among the above parameters, body height, fractures, and BMD were analyzed. RESULTS: Abnormal BMD was observed in 42.9% of women and 23.1% of men. The mean final heights of women and men were 3.7 cm and 7.3 cm lower than the mean expected values, respectively. Fracture history was recorded in 26.7% of women and 35.7% of men. BMD was negatively correlated with parathyroid hormone, FGF23, thyrotropin, and glycated hemoglobin (HbA1c) levels, and positively correlated with testosterone, IGF-1, and corticotropin levels (all P < .05). Moreover, hypothyroidism was associated with lower BMD in both the lumbar spine (P = .024) and the femoral neck (P = .004). Patients with hypothyroidism had a higher percentage of abnormal BMD (P = .016). CONCLUSION: Hypothyroidism, higher HbA1c, and lower adrenocorticotropin were predictors of abnormal BMD in patients with ß-TM. Whether the correction of these factors improves BMD warrants further research.

Fracture types affect clinical outcomes of patients managed within the fracture liaison and osteoporosis medication management services.

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.

Risk Factors for Poor Functional Recovery, Mortality, Recurrent Fractures, and Falls Among Patients Participating in a Fracture Liaison Service Program.

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.

Chronic kidney disease predicts a lower probability of improvement in patient-reported experience measures among patients with fractures: a prospective multicenter cohort study.

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. INTRODUCTION: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

Correction to: Consensus on best practice standards for Fracture Liaison Service in the Asia-Pacific region.

In this article the name of the sixth author, E. Michael Lewiecki was rendered incorrectly. The publisher regrets this error and apologizes for the inconvenience caused.

Consensus on best practice standards for Fracture Liaison Service in the Asia-Pacific region.

The Fracture Liaison Service (FLS) Consensus Meeting endorsed by the International Osteoporosis Foundation (IOF), Asian Federation of Osteoporosis Societies (AFOS), and Asia Pacific Osteoporosis Foundation (APOF) was hosted by the Taiwanese Osteoporosis Association on October 14, 2017. International and domestic experts reviewed the 13 Best Practice Framework (BPF) standards and concluded that all standards were generally applicable in the Asia-Pacific region and needed only minor modifications to fit the healthcare settings in the region. PURPOSE: To review and generate consensus on best practices of fracture liaison service (FLS) in the Asia-Pacific (AP) region. METHODS: In October 2017, the Taiwanese Osteoporosis Association (TOA) invited experts from the AP region (n = 23), the Capture the Fracture Steering Committee (n = 2), and the USA (n = 1) to join the AP region FLS Consensus Meeting in Taipei. After two rounds of consensus generation, the recommendations on the 13 Best Practice Framework (BPF) standards were reported and reviewed by the attendees. Experts unable to attend the on-site meeting reviewed the draft, made suggestions, and approved the final version. RESULTS: Because the number of FLSs in the region is rapidly increasing, experts agreed that it was timely to establish consensus on benchmark quality standards for FLSs in the region. They also agreed that the 13 BPF standards and the 3 levels of standards were generally applicable, but that some clarifications were necessary. They suggested, for example, that patient and family education be incorporated into the current standards and that communication with the public to promote FLSs be increased. CONCLUSIONS: The consensus on the 13 BPF standards reviewed in this meeting was that they were generally applicable and required only a few advanced clarifications to increase the quality of FLSs in the region.

The influence of alendronate and tooth extraction on the incidence of osteonecrosis of the jaw among osteoporotic subjects.

BACKGROUND: Although bisphosphonate-related osteonecrosis of the jaw (ONJ) develops mainly after tooth extractions (TEs), the strength of the association between them and how the existence of the disease among bisphosphonate (BP)-treated osteoporotic patients exposed to TE remain uncertain. METHODS: A nationwide retrospective cohort study investigated the influence of alendronate and TE on the development of ONJ. RESULTS: Incidence of ONJ following long-term alendronate therapy was 262/100,000 person-years, while no event developed in the control group on raloxifene. Overall prevalence of ONJ in osteoporotic subjects receiving alendronate was estimated at 0.34% which rose to 2.16% after TE. Multiple logistic regression analysis, adjusted for the potential confounders, showed TE (adjusted odds ratio, 9.60 [4.33-21.29]), drug duration exceeding 3 years (3.00 [1.33-6.76]), and concomitant rheumatoid arthritis (4.94 [1.64-14.90]) were independent predictors of ONJ. CONCLUSIONS: This article strengthens the relationship between ONJ and BPs. Among osteoporotic patients exposed to alendronate, TE confers a 9.6-fold increased risk for ONJ and it should be performed with caution irrespective of drug duration.

Fracture liaison services improve outcomes of patients with osteoporosis-related fractures: A systematic literature review and meta-analysis.

OBJECTIVES: This systematic review and meta-analysis evaluated the outcomes of patients with osteoporosis-related fractures managed through fracture liaison services (FLS) programs. METHODS: Medline, PubMed, EMBASE, and the Cochrane Library were searched (January 2000-February 2017 inclusive) using the keywords 'osteoporosis', 'fractures', 'liaison', and 'service' to identify randomised controlled trials and observational studies of patients aged ≥50years with osteoporosis-related fractures in hospital, clinic, community, or home-based settings who were managed using FLS. Risk of bias was assessed at outcome level. Meta-analysis followed a random-effects and fixed-effects model. Outcomes of interest were incidence of bone mineral density (BMD) testing, treatment initiation, adherence, re-fractures, and mortality due to osteoporosis treatment. RESULTS: A total of 159 publications were identified for the systematic literature review; 74 controlled studies (16 RCTs; 58 observational studies) were included in the meta-analysis. Overall, 41 of 58 observational studies and 12 of 16 RCTs were considered of high quality. Compared with patients receiving usual care (or those in the control arm), patients receiving care from an FLS program had higher rates of BMD testing (48.0% vs 23.5%) and treatment initiation (38.0% vs 17.2%) and greater adherence (57.0% vs 34.1%). Unweighted average rates of re-fracture were 13.4% among patients in the control arm and 6.4% in the FLS arm. Unweighted average rates of mortality were 15.8% in the control arm and 10.4% in the FLS arm. Meta-analysis revealed significant FLS-associated improvements in all outcomes versus non-FLS controls, with BMD testing increased by 24 percentage points (95% confidence interval [CI] 0.18-0.29), 20 percentage points for treatment rates (95% CI 0.16-0.25), and 22 percentage points for adherence (95% CI 0.13-0.31) and absolute risk of re-fracture reduced by five percentage points (95% CI -0.08 to -0.03) and mortality reduced by three percentage points (95% CI -0.05 to -0.01). CONCLUSION: FLS programs improved outcomes of osteoporosis-related fractures, with significant increases in BMD testing, treatment initiation, and adherence to treatment and reductions in re-fracture incidence and mortality.

The development of Taiwan Fracture Liaison Service network.

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.

Effects of exercise improves muscle strength and fat mass in patients with high fracture risk: A randomized control trial.

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.

Predicting the risk of osteopenia for women aged 40-55 years.

BACKGROUND/PURPOSE: Osteoporosis has been linked to an increased fracture risk and subsequent mortality in the later life. Previous prediction models have focused on osteoporosis in postmenopausal women; however, a prediction tool for osteopenia is needed. Our objective was to establish a prediction model for osteopenia risk in women aged 40-55 years. METHODS: This was a cross-sectional study. A total of 1350 Taiwanese women aged 40-55 years were recruited from a health checkup center from 2009 to 2010. The main outcome measure was osteopenia (-1≥bone mineral density T-score > -2.5). RESULTS: The Osteoporosis Preclinical Assessment Tool (OPAT) developed in this study was based on variables with biological importance to osteopenia and variables that remained significant (p<0.05) in the multivariable analysis, which include age, menopausal status, weight, and alkaline phosphatase level. The OPAT has a total score that ranges from 0 to 7, and categorizes women into high-, moderate-, and low-risk groups. The predictive ability of the OPAT (area under the receiver operating characteristic curve=0.77) was significantly better than that of the Osteoporosis Self-assessment Tool for Asians (area under the receiver operating characteristic curve=0.69). The inclusion of serum total alkaline phosphatase level in the model, which is easy to obtain from routine health checkups, significantly enhanced the sensitivity (McNemar test, p=0.004) for detecting osteopenia in women aged 40-55 years. CONCLUSION: Our findings provide an important tool for identifying women at risk of osteoporosis at the preclinical phase.

Establishing and evaluating FRAX® probability thresholds in Taiwan.

BACKGROUND/PURPOSE: 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.

Characterization of FN1-FGFR1 and novel FN1-FGF1 fusion genes in a large series of phosphaturic mesenchymal tumors.

Phosphaturic mesenchymal tumors typically cause paraneoplastic osteomalacia, chiefly as a result of FGF23 secretion. In a prior study, we identified FN1-FGFR1 fusion in 9 of 15 phosphaturic mesenchymal tumors. In this study, a total of 66 phosphaturic mesenchymal tumors and 7 tumors resembling phosphaturic mesenchymal tumor but without known phosphaturia were studied. A novel FN1-FGF1 fusion gene was identified in two cases without FN1-FGFR1 fusion by RNA sequencing and cross-validated with direct sequencing and western blot. Fluorescence in situ hybridization analyses revealed FN1-FGFR1 fusion in 16 of 39 (41%) phosphaturic mesenchymal tumors and identified an additional case with FN1-FGF1 fusion. The two fusion genes were mutually exclusive. Combined with previous data, the overall prevalence of FN1-FGFR1 and FN1-FGF1 fusions was 42% (21/50) and 6% (3/50), respectively. FGFR1 immunohistochemistry was positive in 82% (45/55) of phosphaturic mesenchymal tumors regardless of fusion status. By contrast, 121 cases of potential morphologic mimics (belonging to 13 tumor types) rarely expressed FGFR1, the main exceptions being solitary fibrous tumors (positive in 40%), chondroblastomas (40%), and giant cell tumors of bone (38%), suggesting a possible role for FGFR1 immunohistochemistry in the diagnosis of phosphaturic mesenchymal tumor. With the exception of one case reported in our prior study, none of the remaining tumors resembling phosphaturic mesenchymal tumor had either fusion type or expressed significant FGFR1. Our findings provide insight into possible mechanisms underlying the pathogenesis of phosphaturic mesenchymal tumor and imply a central role of the FGF1-FGFR1 signaling pathway. The novel FN1-FGF1 protein is expected to be secreted and serves as a ligand that binds and activates FGFR1 to achieve an autocrine loop. Further study is required to determine the functions of these fusion proteins.

Skeletal muscle mass adjusted by height correlated better with muscular functions than that adjusted by body weight in defining sarcopenia.

Sarcopenia, characterized by low muscle mass and function, results in frailty, comorbidities and mortality. However, its prevalence varies according to the different criteria used in its diagnosis. This cross-sectional study investigated the difference in the number of sarcopenia cases recorded by two different measurement methods of low muscle mass to determine which measurement was better. We recruited 878 (54.2% female) individuals aged over 65 years and obtained their body composition and functional parameters. Low muscle mass was defined as two standard deviations below either the mean height-adjusted (hSMI) or weight-adjusted (wSMI) muscle mass of a young reference group. The prevalence of sarcopenia was 6.7% vs. 0.4% (male/female) by hSMI, and 4.0% vs. 10.7% (male/female) by wSMI. The κ coefficients for these two criteria were 0.39 vs. 0.03 (male/female), and 0.17 in all subjects. Serum myostatin levels correlated positively with gait speed (r = 0.142, p = 0.007) after adjustment for gender. hSMI correlated with grip strength, cardiopulmonary endurance, leg endurance, gait speed, and flexibility. wSMI correlated with grip strength, leg endurance, gait speed, and flexibility. Since hSMI correlated more closely with grip strength and more muscular functions, we recommend hSMI in the diagnosis of low muscle mass.