Romosozumab, a humanized
monoclonal antibody that binds and inhibits sclerostin, has the dual effect of increasing bone formation and decreasing
bone resorption. As previously reported in the pivotal FRActure study in postmenopausal woMen with
ostEoporosis (FRAME), women with a T-score of ≤ -2.5 at the total hip or femoral neck received subcutaneous placebo or
romosozumab once monthly for 12 months, followed by open-label subcutaneous
denosumab every 6 months for an additional 12 months. Upon completion of the 24-month primary analysis period, eligible women entered the extension phase and received
denosumab for an additional 12 months. Here, we report the final analysis results through 36 months, including efficacy assessments of new vertebral, clinical, and nonvertebral
fracture; bone mineral density (BMD); and safety assessments. Of 7180 women enrolled, 5743 (80%) completed the 36-month study (2851
romosozumab-to-
denosumab; 2892 placebo-to-
denosumab). Through 36 months, fracture risk was reduced in subjects receiving
romosozumab versus placebo for 12 months followed by 24 months of
denosumab for both groups: new vertebral fracture (relative risk reduction [RRR], 66%; incidence, 1.0% versus 2.8%; p < 0.001), clinical fracture (RRR, 27%; incidence, 4.0% versus 5.5%; p = 0.004), and nonvertebral fracture (RRR, 21%; incidence, 3.9% versus 4.9%; p = 0.039). BMD continued to increase for the 2 years with
denosumab treatment in both arms. The substantial difference in BMD achieved through 12 months of
romosozumab treatment versus placebo was maintained through the follow-up period when both treatment arms received
denosumab. Subject incidence of adverse events, including positively adjudicated serious cardiovascular adverse events, were overall balanced between groups. In conclusion, in postmenopausal women with
osteoporosis, 12 months of
romosozumab led to persistent
fracture reduction benefit and ongoing BMD gains when followed by 24 months of
denosumab. The sequence of
romosozumab followed by
denosumab may be a promising regimen for the treatment of
osteoporosis. © 2018 American Society for Bone and
Mineral Research.