Romosozumab increased bone mineral density (BMD) in postmenopausal women through increased bone formation and decreased bone resorption, according to results of a study published in the Journal of Bone and Mineral Research.
Michael R. McClung, MD, from the Oregon Osteoporosis Center, Portland, Oregon, and colleagues sought to evaluate the efficacy of multiple possible treatment sequences and their effect on BMD. In the parallel-group study, postmenopausal women (n=364) with low BMD (T-score ≤-2.0 at the lumbar spine, total hip, or femoral neck and ≥-3.5 at each of the 3 sites) were randomly assigned to receive either romosozumab or alendronate plus romosozumab for 24 months followed by 12 months of denosumab (60 mg) or placebo. The women received 1 of 5 dosages of romosozumab: 70 mg, 140 mg, or 210 mg once a month or 140 mg or 210 mg every 3 months.
BMD was measured at the lumbar spine and proximal femur using dual-energy x-ray absorptiometry at baseline, at month 3, and every 6 months thereafter. The primary outcome was the percentage change from baseline in BMD at the lumbar spine after 12 months of treatment.
At month 24, the participants receiving romosozumab 210 mg once monthly had the largest gains in BMD at the lumbar spine (11.3% at month 12 and 15.1% at month 24). BMD gain was also seen at the total hip (4.1% at month 12 and 3.7% at month 24) and femoral neck (5.4% at month 12 and 5.2% at month 24). Participants in the 210-mg once-monthly dosage group also experienced increases in the bone formation marker P1NP after the initiation of treatment.
In participants who switched from alendronate to romosozumab 140 mg once a month, BMD at the lumbar spine, total hip, and femoral neck increased by 4.0%, 1.9%, and 1.3%, respectively, at month 12, and by 9.0%, 2.6%, and 2.6% at month 24.
Participants receiving romosozumab 210 mg once per month who were switched to denosumab continued to show a gain in BMD between month 24 and 36. Over the course of the full 36 months of therapy, the average increases in BMD were 19.4% in the lumbar spine and 7.1% at the total hip.
Serious adverse events in the combined romosozumab groups were osteoarthritis, pneumonia, appendicitis, and breast cancer.
Romosozumab treatment in postmenopausal women with low BMD led to significant increases in BMD over 2 years. “Like other non-bisphosphonate drugs for osteoporosis, effectiveness wanes within 1 year after discontinuing therapy, suggesting that following romosozumab with an anti-remodeling drug is important to maintain the skeletal response,” concluded the investigators. “These results support the use of romosozumab as a therapy for postmenopausal women with osteoporosis.”
McClung MR, Brown JP, Diez-Perez A, et al. Effects of 24 months of treatment with romosozumab followed by 12 months of denosumab or placebo in postmenopausal women with low bone mineral density: a randomized, double-blind, phase 2, parallel group study [published online April 25, 2018]. J Bone Miner Res. doi: 10.1002/jbmr.3452