In postmenopausal women at high risk for fracture, treatment with romosozumab for 12 months, followed by alendronate, was associated with significantly fewer hip fractures than treatment with alendronate alone, according to the results of a recent phase 3, international randomized double-blind trial published in the New England Journal of Medicine.
A total of 4093 postmenopausal women (mean age, 74.3 years; 99% with prior osteoporotic fracture at ≥45 years of age; 96.1% with prevalent vertebral fracture) with osteoporosis and a fragility fracture were randomly assigned at a 1:1 ratio to treatment with monthly subcutaneous romosozumab 210 mg or weekly oral alendronate 70 mg for 12 months. After completion of this double-blind phase, patients in both groups received open-label weekly oral alendronate 70 mg until study completion. Primary end points were cumulative incidence of new vertebral fracture at 24 months and cumulative incidence of clinical fracture (nonvertebral and symptomatic vertebral fracture) at time of primary analysis. Secondary end points were bone mineral density at lumbar spine, total hip, and femoral neck at 12 and 24 months, and incidence of nonvertebral fractures at time of primary analysis.
A total of 3654 women (89.3%) completed 12 months of the trial. Mean bone mineral density T scores were −2.96 at the lumbar spine, −2.80 at the total hip, and −2.90 at the femoral neck. During a 24-month period, the risk for new vertebral fracture was 48% lower in the romosozumab-to-alendronate group (127 of 2046 women; 6.2%) vs the alendronate-to-alendronate group (243 of 2047 women, 11.9%; P <.001).
Clinical fractures were reported in 9.7% (198 of 2046) of patients in the romosozumab-to-alendronate group vs 13.0% (266 of 2047) of patients in the alendronate-to-alendronate group, which translated into a 27% lower risk for fracture with romosozumab (P <.001).
The risk for nonvertebral fracture was 19% lower in the romosozumab-to-alendronate group vs the alendronate-to-alendronate group (8.7% [178 of 2046 patients] vs 10.6% [217 of 2047 patients]; P =.04); the risk for hip fracture was 38% lower in romosozumab-to-alendronate group vs the alendronate-to-alendronate group (2.0% [41 of 2046 women] vs 3.2% [66 of 2047 women]; P =.02). The occurrence of adverse events and serious adverse was similar between the 2 groups.
The investigators concluded that rapid gains in bone mineral density from bone-forming treatment with romosozumab were linked to a lower risk for fracture compared with alendronate over the course of 1 year and over the course of romosozumab followed by alendronate. The lower rate of hip fracture with romosozumab followed by alendronate vs alendronate alone challenges the common practice of first-line use of alendronate in women who have sustained a prior fracture.
Saag KG, Petersen J, Brandi ML, et al. Romosozumab or alendronate for fracture prevention in women with osteoporosis. N Engl J Med. 2017;377(15):1417-1427.