Importance: Discontinuation of denosumab without transitioning to another antiresorptive agent results in rapid bone loss and an increased risk of fracture. Previous randomized studies reported inconsistent results regarding the efficacy of zoledronate as sequential therapy.Objective: To investigate the use of sequential therapy with zoledronate to prevent bone loss and decreased bone mineral density (BMD) after denosumab discontinuation in the first year.Design, Setting, and Participants: The Denosumab Sequential Therapy prospective, open-label, parallel-group randomized clinical trial was conducted at a referral center and 2 affiliated hospitals in Taiwan. Recruitment was conducted from April 1, 2019, to May 31, 2021, and a 2-year follow-up was planned. The trial included postmenopausal women and men aged 50 years or older who received regular denosumab treatment for at least 2 years and did not have previous exposure to other antiosteoporosis medication or meet other exclusion criteria.Intervention: Participants were assigned via stratified randomization to 1 of 2 groups: group A received continuous denosumab treatment (60 mg twice yearly) as the positive control, whereas group ZOL received 1 dose of zoledronate (5 mg) in the first year.Main Outcomes and Measures: The coprimary outcomes were BMD percentage changes in the lumbar spine (LS-BMD), total hip (TH-BMD), and femoral neck (FN-BMD), respectively. An intention-to-treat analysis was performed.Results: This study included 101 patients (95 women [94.1%]; median age, 72.0 [IQR, 67.0-76.0] years). There were 25 patients in group A (23 women [92.0%]; median age, 74.0 [IQR, 70.0 to 78.0] years) and 76 in group ZOL (72 women [94.7%]; median age, 71.0 [IQR, 65.7 to 76.0] years). In the first year, group ZOL had a significant median decrease in LS-BMD (−0.68% [IQR, −3.22% to 2.75%]) compared with group A (1.30% [IQR, −0.68% to 5.24%]) (P = .03). No significant differences between groups A and ZOL were observed for TH-BMD (median, 1.12% [IQR, −0.06% to 2.25%] vs 0% [−1.47% to 2.15%]) (P = .24) and FN-BMD (median, 0.17% [IQR, −2.29% to 2.90%] vs 0.18% [−2.73% to 3.88%]) (P = .71). We observed a significant difference in the median LS-BMD percentage change for the ZOL subgroup with 3 or more years of denosumab treatment before enrollment (−3.20% [IQR, −7.89% to 0.68%]) compared with group A (1.30% [IQR, −0.68% to 5.24%]) (P = .003).Conclusions and Relevance: In this randomized trial of sequential therapy after denosumab discontinuation, bone loss was observed in LS-BMD in the first year among patients receiving zoledronate. A longer duration of denosumab treatment was associated with a further decrease in LS-BMD after zoledronate sequential therapy. Further randomized clinical trials and large-scale studies that investigate the strategies of sequential therapy after long-term denosumab treatment are needed.Trial Registration: ClinicalTrials.gov Identifier: NCT03868033

Background: Monitoring and improving intrinsic capacity (IC) and well-being are essential for older adults to maintain functional abilities. However, evidence of effective interventions to improve IC and happiness is scarce. This study examined the effects of multicomponent interventions in the Healthy Longevity and Ageing in Place (HOPE) randomised controlled trial on IC and happiness among rural community-dwelling older adults. Methods: This cluster randomised trial was conducted in rural communities in Taiwan (NCT05104034). Participants aged ≥50 were enrolled from September 2021 to April 2022 and randomly assigned by community level to one of three groups: multicomponent integrated care (MIC), osteoporosis care (OC) and usual care (UC). MIC included osteoporosis, sarcopenia and polypharmacy care, along with exercise and nutritional support. OC was a resource-conservative, focusing on osteoporosis screening and treatment alone. IC and happiness were measured at baseline and 12 months after follow-up. IC was assessed across cognition, locomotion, vitality, sensory and psychological domains per World Health Organization Integrated Care for Older People (ICOPE) guidelines. Happiness was measured using the 10-item Chinese Happiness Inventory. Generalised estimating equations were used to estimate the effect of the intervention. Results: 567 residents were recruited from 30 congregate meal service centres. Mean IC score increased across all the groups, though the happiness score decreased. Compared to UC, the MIC group exhibited a significantly greater improvement in IC scores (adjusted estimate = 0.30, standard error (SE) = 0.11, P = .01), whereas OC did not show significant effects. Smaller reductions in happiness scores were observed in both the MIC (adjusted estimate = 1.46, SE = 0.48, P = .003) and OC groups (adjusted estimate = 0.95, SE = 0.48, P = .05). Conclusion: MIC, including osteoporosis and pharmaceutical care, along with exercise and nutritional support, is an effective strategy to enhance IC and happiness compared to osteoporosis treatment alone and UC. This underscores the importance of comprehensive strategies for promoting healthy ageing in rural communities.

Osteoporotic fracture introduce enormous societal and economic burden, especially for long-term care residents (LTCRs). Although osteoporosis prevention for LTCRs is urgently needed, obstacles such as frail status and inconvenient hospital visits hurdled them from necessary examinations and diagnoses. We aimed to test 10 existing osteoporosis screening tools (OSTs), which can be easily used in institutions and serve as a prediction, for accurately determining the outcome of a Taiwan's National Health Insurance (NHI)-reimbursed anti-osteoporosis medications (AOMs) application for LTCRs. This prospective analysis recruited 444 patients from LTC institutions between October 2018 and November 2019. Predictions of whether the NHI-reimbursed AOMs criteria was met were tested for 10 OSTs. The results of OSTs categorized into self-reported or validated based on previous fracture history were self-reported by LTCRs or validated by imaging data and medical records, respectively. The receiver operating characteristic curve and the optimal cut-off points for LTCRs based on Youden's index were explored. Overall, the validated OSTs had a higher positive predictive value (PPV) and negative predictive value (NPV) summation than the corresponding reported OSTs. The validated FRAX-Major was the best OST (PPV = 63.6%, NPV = 82.4% for the male group and, PPV = 78.8%, NPV = 90.0% for the female group). After applying the optimum cut-off derived from Youden's index, the validated FRAX-Major (PPV = 75.4%, NPV = 92.0%)) remained performed best for men. In female population, validated FRAX-Major (PPV = 87.2%, NPV = 84.1%) and validated osteoporosis prescreening risk assessment (OPERA; PPV = 96.1%, NPV = 79.7%)) both provided good prediction results. FRAX-Major and OPERA have better prediction ability for LTCRs to acquire NHI-reimbursed AOMs. The validated fracture history and adjusted cut-off points could prominently increase the PPV during prediction.

Real-world cost and effectiveness analyses of the anti-osteoporosis medications (AOM) using a nationwide database in Asia were limited. The aim of this study was to evaluate the cost and effectiveness of AOMs therapy under the reimbursement of National Health Insurance in Taiwan. Using Taiwan's National Health Insurance Research Database, patients who had hospitalization due to incident hip fractures with related operation between 2008 and 2017 were identified as our study population. Patients who initiated AOMs within 1 year post incident hip fracture were matched with those did not according to the propensity score. The direct medical cost and subsequent fracture within three years were estimated. Statistically significant differences of risk for subsequent fracture between the AOM and non-AOM groups were estimated using the COX proportional hazards model. All costs were presented as New Taiwan Dollars (NTD). There were 27,357 new hip fracture patients who initiated AOMs, and 76% of them were women with a mean age of 77.7 years. Among patients ages ≥70 who encountered hip fractures, those who initiated AOMs experienced fewer non-vertebral fractures (HR = 1.07 (1.02-1.13), p = 0.0114 for those ages 70-79 years old; HR = 1.11 (1.06-1.17), p < 0.0001 for those ages ≥80 years) and mortality (HR = 1.18 (1.14-1.22), p < 0.0001 for those ages 70-79; HR = 1.20 (1.16-1.23), p < 0.0001) within 3 years post incident fracture; meanwhile, consuming fewer medical resources in the national insurance healthcare system. (Increment cost = -16011.2 NTD, p = 0.0248 for those ages 70-79; Increment cost = -17257.9 NTD, p = 0.0032 for those ages ≥80 years) CONCLUSION: Overall, under Taiwan's national health insurance, the use of AOMs is cost-saving, especially in the population aged ≥70 years. The finding of this research was valuable for policymakers in considering healthcare policy promotion and resource allocation in the future.