Osteoporosis Drug Significantly Reduced Fractures Compared to Traditional Treatment

Unlike previous romosozumab studies, this study showed the drug’s benefits beyond vertebral fractures—but cardiovascular risk puts FDA approval on hold.

A new osteoporosis drug may be more effective at preventing fractures and improving bone density in high-risk patients than the typical first-line therapy, according to findings published September 2017 in The New England Journal of Medicine.
Older woman reading information on her tablet computer with a look of excited anticipation as she sits on a couchA new osteoporosis drug may be more effective at preventing fractures and improving bone density in high-risk patients than the typical first-line therapy. Photo Source: 123RF.com.
The trial directly compared 2 osteoporosis drugs: alendronate and romosozumab. Alendronate (Fosamax, Binosto, Fosamax Plus D) is an established anti-resorptive agent often prescribed as a first-line osteoporosis treatment. Romosozumab (Evenity) is a new bone-forming monoclonal antibody that blocks sclerostin, which results in rapid bone formation and lower bone resorption.

While romosozumab appears to be an effective preventive force against osteoporosis fractures, a possible link to serious cardiovascular risk has stalled the drug’s U.S. Food and Drug Administration (FDA) approval.

Head-to-Head Drug Comparison

In this trial, researchers randomly placed 4,093 postmenopausal women (average age 74.3 years) with osteoporosis and a history of fracture into 1 of 2 groups: Either the patient would receive monthly subcutaneous romosozumab (210 mg) or weekly oral alendronate (70 mg) for 12 months. At the completion of the 12-month treatment, all patients received 12 months of alendronate.

Over 24 months, the authors observed a 48% reduced risk of new vertebral fractures in the romosozumab-to-alendronate group (6.2%, or 127 of 2,046 patients) compared to the exclusively alendronate group (11.9%, or 243 of 2,047 patients) (P < 0.001).

Incidence of clinical fractures (non-vertebral and symptomatic vertebral fracture) was 27% lower in the romosozumab-to-alendronate group (9.7%, or 198 of 2,046 patients) compared to the exclusively alendronate group (13.0%, or 266 of 2,047 patients) (P < 0.001).

And, unlike previous romosozumab studies, this trial showed the drug’s benefits beyond vertebral fractures.

“Although the placebo-controlled Fracture Study in Postmenopausal Women with Osteoporosis (FRAME) showed that 12 months of romosozumab had preventive effects with respect to vertebral and clinical but not non-vertebral fractures (potentially influenced lower baseline fracture risk), the present trial assessed efficacy in a higher-risk population and showed broad beneficial effects on fracture risk as compared with a commonly used active drug,” the authors wrote.

Indeed, this trial showed that the romosozumab group boasted a 19% lower risk of non-vertebral fractures versus the exclusively alendronate group (8.7%, or 178 of 2,046 patients versus 10.6%, or 217 of 2,047 patients; P = 0.04). The romosozumab patients also had a 38% reduced risk of hip fracture versus the exclusively alendronate group (2.0%, or 41 of 2,046 patients versus 3.2%, or 66 of 2,047 patients; P = 0.02).

Cardiovascular Events Thwart Romosozumab’s FDA Approval

Overall, the authors observed a “balanced” dispersion of adverse events between the 2 groups. However, they noted that serious cardiovascular adverse events more frequently occurred in the romosozumab group than in the alendronate group, namely cardiac ischemic and cerebrovascular events.

The researchers observed that 2.5%, or 50 patients, of the romosozumab group, had a serious cardiovascular event compared to 1.9%, or 38 patients, of the alendronate group (odds ratio, 1.31; 95% CI, 0.85 to 2.00).

While the cause of these cardiovascular events is unknown, the authors noted a possible association between sclerostin inhibition and cardiovascular risk.

“Sclerostin is constitutively expressed in the aorta and up-regulated in foci of vascular and valvular calcification,” the authors wrote. “The function of sclerostin in the vasculature is unknown. Although sclerostin may function as a negative regulator of vascular calcification and sclerostin inhibition could promote vascular calcification, studies have shown conflicting results.”

The elevated cardiovascular risk is largely to blame for the FDA’s rejection of romosozumab in July 2017. Regulators have asked for more data before reconsidering the drug’s approval.

Updated on: 09/12/19
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