Abstract
INTRODUCTION: Osteoporosis (OP) is a systemic skeletal disorder that increases fragility and susceptibility to fractures. Despite the availability of teriparatide for the treatment of patients with acute fractures with better efficacy, its long-term daily injection and high cost limit its broader use among a wider patient population, especially for those living in low- and middle-income countries. This study aims to evaluate the efficacy of a novel sequential treatment with teriparatide daily for 6 months followed by denosumab every 6 months for another 18 months, in comparison with denosumab monotherapy every 6 months for 24 months, in reducing the risk of fractures in patients with newly diagnosed osteoporotic fractures. The study will also explore the possible difference between two sequential treatments (shifting to denosumab treatment at 6 or 12 months) in their effect on increasing bone mineral density (BMD). METHODS AND ANALYSIS: This study is designed as a multicentre, open-label, randomised controlled trial among 2478 patients with newly diagnosed osteoporotic fractures from 58 hospitals across China. Participants will be randomly assigned in a 10:10:1 ratio to three treatment groups: 24 months of denosumab monotherapy, early sequential treatment (teriparatide for 6 months followed by denosumab for 18 months) and late sequential treatment (teriparatide for 12 months followed by denosumab for 12 months). The primary outcome is the incidence of vertebral fractures over 24 months of treatment. Secondary outcomes include changes in BMD at the lumbar spine, total hip and femoral neck, changes in bone turnover markers (β-carboxy-terminal telopeptide of type 1 collagen and procollagen type 1 N-terminal propeptide), treatment adherence and cost-effectiveness. Follow-up assessments are scheduled at 3, 6, 9, 12, 18 and 24 months post-randomisation for primary and secondary outcomes, and biannually afterwards for the primary outcome. ETHICS AND DISSEMINATION: The study protocol has been registered on ClinicalTrials.gov and has received ethical approval from the Peking Union Medical College Hospital Medical Science Research Ethics Committee (1-22PJ939). The findings will be disseminated through peer-reviewed scientific journals. TRIAL REGISTRATION NUMBER: NCT05866029.