Romosozumab Decreases Risk of Fractures in Women With Osteoporosis

 

In postmenopausal women with osteoporosis, a 12-month treatment with romosozumab prior to alendronate therapy results in a lower risk of fractures.

Jennifer R. Mobley, DVM

July 16, 2019 – The addition of romosozumab 12 months prior to aldendronate therapy reduces the risk of fractures in postmenopausal women with osteoporosis, according to research.

Kenneth G. Saag, MD, with the University of Alabama at Birmingham, and colleagues reported their findings in the October 12, 2017, issue of the New England Journal of Medicine.

Over the past two decades, antiresorptive agents such as alendronate have been traditionally used to treat osteoporosis in postmenopausal women. Romosozumab, a monoclonal antisclerostin antibody, has a dual effect as it promotes ossification while decreasing bone resorption.

“There are few head-to-head studies of osteoporosis therapy with fracture end points, and only one trial evaluating bone-building versus antiresorptive therapy was designed with fracture as the primary end point,” Saag reported. His team evaluated fracture risk as an end point when the two medications were administered in conjunction.

Postmenopausal women aged 55 to 90 years with low bone mineral density or previous fracture history were randomly assigned to two groups. For the first 12 months, participants either received a monthly subcutaneous injection of romosozumab (n = 2046) or oral alendronate (n = 2047). Both groups were then administered alendronate only for the following 12 months. The primary endpoint was the cumulative incidence of new vertebral fractures and nonvertebral fractures. Secondary endpoints included the occurrence of other nonvertebral fractures, including hip fractures, at 24 months post-initiation of therapy.

The women who were in the romosozumab-to-alendronate group had a 48% lower risk of new vertebral fractures (P = 0.04) and a 19% lower risk of nonvertebral fractures (P < 0.001) compared with those who were in the alendronate-only group. Furthermore, the risk of hip fractures was lowered by 38% in the romosozumab-to-alendronate group. (P = 0.02)

Serious cardiovascular events, including cardiac ischemia and cerebrovascular events, were reported at similar rates in both groups with 50 patients (2.5%) in the romosozumab-to-alendronate group and 38 patients (1.9%) in the alendronate-only group. Other adverse events included osteoporosis of the jaw and atypical femoral fracture, which were observed during the open-label, alendronate-only period in both groups.

The benefits of increased bone density with the addition of romosozumab to the common alendronate treatment protocol show promising results. However, due to the possibility of sclerostin inhibition being associated with adverse cardiovascular events, further research is needed. Dr. Saag and colleagues concluded that “in postmenopausal women with osteoporosis who were at high risk for fracture, romosozumab treatment for 12 months followed by alendronate resulted in a significantly lower risk of fracture than alendronate alone.”

This study was supported by Amgen, Astellas Pharma, and UCB Pharma. A complete list of disclosures is available in the full text of the article.

N Engl J Med. Published on October 12, 2017.