Journal Article

Study protocol for the ROLEX-DUO randomised placebo-controlled trial: ROmosozumab Loaded with EXercise – DUal effects on bone and muscle in postmenopausal Osteoporosis and Osteopenia

Kumar, Shejil, Nery, Liza, Byth, Karen, Fuller, Oliver K, Elhindi, James, Clifton-Bligh, Roderick J, Wood, Cameron, Beck, Belinda R, Girgis, Christian M

2024

Overview

IntroductionNovel strategies are needed to address the rising burden of osteoporosis and fragility fractures. High-intensity resistance and impact (HiRIT) exercise has shown benefit in improving bone density in postmenopausal women with osteoporosis/osteopenia. Whether HiRIT can enhance the therapeutic effects of osteoporosis pharmacotherapy has not been established. ROLEX-DUO is a randomised controlled trial designed to assess the efficacy of romosozumab on various bone and muscle outcomes in combination with different exercise interventions in women with postmenopausal osteoporosis/osteopenia.Methods and analysisROLEX-DUO is an 8-month randomised placebo-controlled trial conducted at two tertiary referral centres for patients with osteoporosis/osteopenia in Sydney, New South Wales, Australia. The study is implementing the combination of romosozumab or placebo with different forms of exercise in postmenopausal women with osteoporosis/osteopenia without recent fragility fracture (n=102). Eligible women will be randomised 1:1:1 into one of three groups: (1) romosozumab with supervised HiRIT, (2) romosozumab with unsupervised low-intensity exercise or (3) placebo with unsupervised low-intensity exercise. Co-primary outcomes are the mean percentage change in lumbar spine bone mineral density (BMD), and mean change in five times sit-to-stand test performance (seconds) at 8 months. Secondary/exploratory outcomes include BMD changes at the femoral neck, total hip and distal radius, three-dimensional dual-energy X-ray absorptiometry (DXA) hip outcomes, DXA-derived lean and fat mass, serum markers of bone turnover (procollagen type 1 peptide, C-telopeptide of type 1 collagen) and bone biomarkers (dickkopf-1), serum extracellular vesicle analyses, 36-Item Short Form Survey (SF-36) quality-of-life scores, Menopause-Specific Quality Of Life (MENQOL) Questionnaire menopause symptom burden scores, number of falls and fractures. Mixed-effects models will be performed to compare longitudinal outcome results between groups using intention-to-treat analysis.Ethics and disseminationThe trial was approved by the Northern Sydney Local Health District Human Research Ethics Committee (2022/ETH01794, protocol V.8, dated 03 July 2024). Participants will provide written informed consent prior to inclusion. Findings will be disseminated via peer-reviewed journals, scientific conferences and summary reports to funding bodies.Trial registration numberACTRN12623000867695.

• Publisher: British Medical Journal Publishing Group,BMJ Publishing Group LTD,BMJ Publishing Group
• Subject: Aged / Antibodies, Monoclonal - administration & dosage / Antibodies, Monoclonal - therapeutic use / Bone density / Bone Density - drug effects / Bone Density Conservation Agents - administration & dosage / Bone Density Conservation Agents - therapeutic use / Bone Diseases, Metabolic - drug therapy / calcium & bone / Clinical outcomes / clinical trial / Diabetes / diabetes & endocrinology / Diabetes and endocrinology / Drug therapy / Exercise Therapy - methods / Female / Fractures / Humans / Hypotheses / Middle Aged / Monoclonal antibodies / Muscle, Skeletal - drug effects / Muscle, Skeletal - physiopathology / Osteoporosis / Osteoporosis, Postmenopausal - drug therapy / Patients / Quality of Life / Randomized Controlled Trials as Topic / Resistance Training - methods / Womens health