Osteoporosis Drug Romosozumab Defies Cardiovascular Concerns in New Analysis

Research suggests no increased heart risk compared to similar treatments, challenging existing warnings

New findings indicate the osteoporosis medication romosozumab may not carry the elevated cardiovascular risks previously flagged by a significant regulatory warning. The study, presented at a major endocrine conference, offers a contrasting perspective to earlier clinical trial data.

Challenging the Black Box Warning

A comprehensive analysis of real-world patient data has revealed that romosozumab, a novel anabolic osteoporosis treatment, did not demonstrate an increased incidence of major adverse cardiovascular events when compared to other anabolic agents like teriparatide or abaloparatide. The research team highlighted that these results directly contradict the concerns that led to a black box warning on the drug.

“These findings suggest there is no heightened risk for major adverse cardiovascular events in patients with osteoporosis treated with romosozumab compared to the anabolic agents teriparatide or abaloparatide.”

—Maxim John Levy Barnett, MD, Jefferson-Einstein Hospital

The researchers stated that further observational data is needed to solidify these conclusions, which could potentially lead to the removal of the black box warning. Romosozumab, a monoclonal antibody, works by stimulating bone formation and decreasing bone resorption, improving bone mineral density and reducing fracture risk.

Study Methodology and Surprising Outcomes

To investigate the cardiovascular safety profile, researchers examined data from the TriNetX database, involving nearly 14,300 patients treated with romosozumab and a comparable number receiving teriparatide or abaloparatide. After rigorous propensity score matching to account for various health factors, the analysis tracked patients for an average of five years.

Surprisingly, the romosozumab group exhibited a nonsignificant trend toward a reduced risk of overall cardiovascular incidents. More significantly, the study found notably lower rates of ischemic heart disease and acute myocardial infarction among those on romosozumab. Heart failure rates were also substantially reduced in this group.

“After propensity-score matching, there was still a significant reduction [with romosozumab], which was a surprise. Three out of the 4 outcomes actually showed a significant decrease in risk with romosozumab.”

—Maxim John Levy Barnett, MD, Jefferson-Einstein Hospital

“There is no substantial evidence for cardiovascular risk and this medication; nonetheless, the black box warning is present,” noted Dr. Barnett.

Expert Commentary and Clinical Implications

The findings have drawn attention from endocrinology experts. Dr. Tiffany Kim of the University of California, San Francisco, commented that these results contribute to a growing body of evidence questioning romosozumab’s association with increased cardiovascular risk. She emphasized the impact of black box warnings on clinical practice and patient discussions.

“This study adds to the reassuring literature that romosozumab may not be associated with increased risk of cardiovascular disease.”

—Tiffany Kim, MD, University of California, San Francisco

Dr. Kim acknowledged that while the study controlled for many comorbidities, unmeasured factors might influence prescribing decisions and potentially be linked to cardiovascular disease. She concluded that while valuable, observational studies can’t offer definitive proof.

Despite the new findings, regulatory agencies typically require extensive data before altering drug warnings. The US Food and Drug Administration (FDA) initially issued the black box warning based on clinical trials, including the ARCH study, which suggested a higher risk of serious cardiovascular events. Romosozumab remains contraindicated in patients with a history of recent heart attack or stroke, or those with hypocalcemia.