Randomised clinical trial evaluating the efficacy and safety of denosumab 6-monthly vs. 9-monthly in postmenopausal osteoporosis

Denosumab is an established anti-resorptive therapy approved for the treatment of postmenopausal osteoporosis and is conventionally administered as a 60 mg subcutaneous injection every 6 months. Emerging clinical observations, including data from our center, suggest that bone turnover markers may remain adequately suppressed beyond 6 months in a subset of patients, raising the possibility that a longer dosing interval may maintain efficacy while reducing cumulative drug exposure and cost. However, no randomized controlled trial has systematically compared different dosing intervals of denosumab.

This is a prospective, randomized, open-label, blinded-endpoint (PROBE) clinical trial designed to compare the efficacy and safety of denosumab administered every 6 months versus every 9 months in postmenopausal women with osteoporosis. A total of 100 eligible postmenopausal women will be randomized in a 1:1 ratio to receive denosumab 60 mg subcutaneously either every 6 months (standard schedule) or every 9 months (extended interval), along with calcium and vitamin D supplementation, over an 18-month treatment period. Participants will then be followed for an additional 12 months to assess post-treatment outcomes.

The primary outcome is the percent change in bone mineral density at the lumbar spine and femoral neck at 24 months. Co-primary outcome include incident fragility fractures while secondary outcomes include changes in bone turnover markers, bone microarchitecture assessed by HR-pQCT and trabecular bone score, and characterization of osteoclast lineage cells. During follow-up, participants will be closely monitored for biochemical or densitometric evidence of rebound bone turnover. Predefined rescue criteria will guide the use of zoledronate to mitigate rebound-associated bone loss.

The study aims to generate evidence on whether an extended dosing interval of denosumab is non-inferior to the standard schedule with respect to skeletal outcomes, while maintaining safety, in postmenopausal women with osteoporosis.