The results of a large-scale multi-centre international phase 3 clinical trial shows that an innovative drug combination can significantly lower the risk of fracture among high risk patients with osteoporosis
A regimen of a novel bone anabolic medication (which builds bone mass) followed by an antiresorptive agent (which maintains bone mass) has been shown to significantly reduce the risk of fracture among post-menopausal women with severe osteoporosis, according to results of a clinical trial published in The New England Journal of Medicine.
Over a two-year period, 4,093 women with osteoporosis and a fragility fracture were randomly assigned to one of two groups. The first received romosozumab for a year, a new monoclonal antibody against sclerostin that is effective at rapidly building bone mass by increasing bone formation and decreasing bone resorption. This was followed by alendronate, an antiresorptive agent commonly used as first-line therapy for osteoporosis, that maintains existing levels of bone mass. The second group received only alendronate. The women who received romosozumab followed by alendronate were observed to have a 48% lower rate of new vertebral fractures when compared with those who only received alendronate. Moreover, the former group had a 19% lower risk of nonvertebral fractures, and 38% lower risk of hip fracture than those in the latter group.
“Keeping patients at a constant bone mass isn’t adequate when they are already suffering from osteoporosis and their bones aren’t strong enough to resist fracture,” said Dr. Andrew Karaplis, a Professor of Medicine at McGill University who researches metabolic bone disease at the Lady Davis Institute and treats osteoporotic patients at the Jewish General Hospital, one of the centres participating in this phase 3 clinical trial. “We anticipated less fractures if we first succeeded in increasing the patient’s bone mass followed by a regimen to sustain it.”
Dr. Karaplis characterized the study’s results as a “significant breakthrough” in treating osteoporosis, adding that the findings would affect how he treats his patients.
One safety concern did emerge over the course of the trial. During the first year, serious cardiovascular events were observed more frequently in the romosozumab-alendronate group (50 of 2040 patients, or 2.5%, as compared with 38 of 2014, or 1.9%, in the alendronate only group).
“Although the numbers are relatively small, this is a signal that requires further clarification,” said Dr. Karaplis. “There exist theoretical considerations that sclerostin inhibition is associated with cardiovascular risk. Alternatively, alendronate could be cardioprotective as shown in some studies. So, we need to look more deeply as to the cause of the observed imbalance in cardiovascular events and be cautious about the patients we choose to treat with romosozumab, at least for now.”
Osteoporosis is a serious condition affecting both women and men, with post-menopausal women being particularly susceptible. The progressive loss of bone mass puts those with the condition at greater risk for fracture. To date, there is no effective treatment or cure, which is why the promise of this study, which demonstrates that bone mass can be regenerated with romosozumab and sustained with antiresorptives, is of such importance.
“Romosozumab or Alendronate for Fracture Prevention in Women with Osteoporosis,” Kenneth G. Saag, M.D., Jeffrey Petersen, M.D., Maria Luisa Brandi, M.D., Andrew C. Karaplis, M.D., Ph.D., Mattias Lorentzon, M.D., Ph.D., Thierry Thomas, M.D., Ph.D., Judy Maddox, D.O., Michelle Fan, Ph.D., Paul D. Meisner, Pharm.D., and Andreas Grauer, M.D., New England Journal of Medicine, 2017; 377:1417-1427 October 12, 2017 DOI: 10.1056/NEJMoa1708322