Sequential Treatment With Romosozumab Followed by Denosumab vs. Zoledronic Acid for Gains in HIP BMD

Osteoporosis is associated with a high risk of fractures, disability, loss ofindependence, and excess mortality. Zoledronic acid is an established first‐linetreatment in Sweden, but many patients at high fracture risk remain at substantialresidual fracture risk. Short‐course treatment with romosozumab followed by denosumabproduces large increases in bone mineral density, but has not been directly compared withzoledronic acid.STRONG‐HIP is a multicentre, randomized, active‐controlled phase 4 trial in 216postmenopausal women aged 60 years or older with osteoporosis and high fracture risk.Participants are randomized 1:1 to receive romosozumab 210 mg monthly for 3 monthsfollowed by denosumab 60 mg every 6 months, or zoledronic acid 5 mg intravenously atbaseline and Month 12.The primary objective is to determine whether the romosozumab‐denosumab sequence producesa greater percentage increase in total hip bone mineral density from baseline to Month 24than zoledronic acid. Secondary outcomes include total hip and lumbar spine BMD atearlier time points, vertebral and clinical fractures, bone turnover markers, safety,health‐related quality of life, and health‐economic outcomes. A mechanistic substudy willassess bone microarchitecture and estimated strength using HR‐pQCT.Participants are followed for 24 months in the main study and may enter an optionalextension with follow‐up to Month 48 to assess the durability of treatment effects.