INTRODUCTION: The aim of this study was to use direct bone mineral density (BMD) outcomes for romosozumab versus teriparatide to estimate relative risks (RRs) of fracture in postmenopausal women with osteoporosis. The approach is justified by the significant linear relationship between percentage total hip BMD change from baseline and RRs of hip and vertebral fracture on the log scale shown by a meta-regression conducted by the Foundation for the National Institutes of Health (FNIH).
METHODS: The STRUCTURE trial provides a 3.4% difference in total hip BMD change from baseline at 12 months for romosozumab versus teriparatide in patients previously treated with bisphosphonates. This value was translated into RRs of hip, vertebral, and nonvertebral fracture using slopes from the FNIH meta-regression. Uncertainty around resulting estimates was derived by error propagation. As a sensitivity analysis, BMD efficacy for romosozumab versus teriparatide was taken from a phase II trial (2.8% difference in total hip BMD change from baseline) to explore outcomes for a treatment-naïve population.
RESULTS: In the base case, RRs of fracture (with 95% confidence intervals) for romosozumab versus teriparatide were 0.75 (0.60 to 0.95), 0.53 (0.37 to 0.76), and 0.90 (0.78 to 1.03) for hip, vertebral, and nonvertebral fracture, respectively. The sensitivity analysis using phase II trial data yielded RRs of 0.79 (0.64 to 0.97), 0.59 (0.43 to 0.82), and 0.91 (0.81 to 1.03) for hip, vertebral, and nonvertebral fracture. Validation of the approach using romosozumab trials reporting both BMD and fracture outcomes at 12 months (FRAME, ARCH) showed consistency between BMD-predicted and observed RRs of fracture.
CONCLUSION: Results indicate that the BMD benefit of romosozumab versus teriparatide translates into clinically meaningful fracture reductions for bisphosphonate pre-treated and treatment naïve patients.