Abstract
BACKGROUND: Postmenopausal osteoporosis is a highly prevalent disease associated with substantial morbidity and mortality. The most recently introduced osteoporosis medication is romosozumab, a monoclonal antibody with a unique mechanism of action that increases bone mineral density (BMD) more than other agents by both stimulating new bone formation and inhibiting resorption. The drug's stimulation of bone formation, however, wanes after several months. The use of romosozumab is limited by cost, the inconvenience of monthly clinic-administered injections, and its cardiovascular risk profile. In this trial, we aimed to test the hypothesis that a shorter course of romosozumab might be equally effective as the standard regimen.
METHODS: We did a 12-month, prospective, open-label, randomised, controlled, non-inferiority trial of 50 postmenopausal women at high risk of fracture. The study was done at a single academic medical centre in the USA. Participants were randomly assigned to receive 3 months of romosozumab (210 mg by subcutaneous injection, monthly) followed by 9 months of denosumab (60 mg by subcutaneous injection, every 6 months; 3-month ROMO group) or 12 months of romosozumab (12-month ROMO group). The primary endpoint was the percentage change in total hip BMD. The non-inferiority threshold was set at 2%. The trial was registered at ClinicalTrials.gov, NCT05010590.
FINDINGS: Between March 2, 2022, and May 2, 2023, we screened 188 participants. Of those, 102 (54%) were ineligible and 36 (19%) declined to participate. We randomly assigned 50 participants to either the 3-month ROMO group (24 [48%] participants) or the 12-month ROMO group (26 [52%] participants). Study participants completing at least one post-baseline visit were included in the analysis (modified intention-to-treat analysis). The mean age of participants was 69·6 years (SD 4·5). The mean 12-month change in total hip BMD was 5·7% (SD 3·3) in the 3-month romosozumab group and 6·0% (3·2) in the 12-month romosozumab group, meeting the prespecified non-inferiority threshold. Adverse events (back pain, cough, fatigue, headache, joint pain, muscle cramps, muscle pain, palpitations, paraesthesia, reaction at injection site, rhinorrhoea, skin rash, and swelling) were balanced between groups.
INTERPRETATION: In postmenopausal women at high risk of fracture, 3 months of romosozumab followed by 9 months of denosumab was non-inferior to 12 months of romosozumab in increasing total hip BMD. Given the expense, injection burden, and potential adverse effects of romosozumab, this abbreviated approach could broaden access to this uniquely effective therapy.
FUNDING: US National Institute of Arthritis and Musculoskeletal and Skin Diseases and US National Center for Advancing Translational Science.