The FDA Biomarker Qualification Program approved changes in hip bone mineral density (BMD) after treatment to serve as a surrogate endpoint in place of bone fractures in anti-osteoporosis drug clinical trials involving postmenopausal women.

The qualification approval was based on the results of the Study to Advance BMD as a Regulatory Endpoint (SABRE). The SABRE research team set out to find measures that determine an anti-osteoporosis drug’s power to lower the prevalence of fractures. SABRE included data from 52 trials with over 160,000 participants. The findings demonstrated a strong relationship between a treatment-related rise in hip BMD and a decline in fracture risk.

“Drugs for reducing fractures are available, but treatment rates have markedly declined due to concerns about very rare side effects, inconvenient dosing, and limited effectiveness against some types of fractures,” Dennis Black, PhD, of the University of California San Francisco, said in a press release. “This FDA decision will help address the treatment gap for osteoporosis by accelerating development of new therapies and providing more options to patients and clinicians,” Black concluded.

Previous studies have used fractures as a primary endpoint when evaluating anti- osteoporosis drugs. Prior trials often involved 7705 to 16,071 participants and took years to complete. Granting BMD surrogate endpoint status as measured by dual-energy x-ray absorptiometry (DEXA) could be a step toward more time- and cost-efficient trials.

There were several pieces of evidence that were used to back this qualification.

Notably, data from SABRE highlighted a statistically significant relationship between treatment-associated declines in five fracture types (vertebral, nonvertebral, hip, all clinical, and all fractures) and the average percentage change in total BMD over 2 years.

Higher BMD was linked with greater fracture declines for each type of fracture. The coefficient of determinations (R-square) along with the corresponding 95% CIs were 0.71 (95% CI, 0.32-0.83) for all clinical fractures, 0.41 (95% CI, 0.02-0.65) for hip fracture, 0.53 (95% CI, 0.11-0.72) for nonvertebral fractures, and 0.73 (95% CI, 0.33-0.84) for vertebral fractures.

There were 16 randomized controlled trials that all pointed to an association between fracture risk reductions and BMD changes. These trials evaluated anabolic drugs and antiresorptive agents with varying mechanisms of actions.

The qualification specifies that changes in hip BMD are to be evaluated using DEXA, which is a noninvasive and cost-effective imaging test. Changes in calcium and other mineral levels in the bones are monitored from baseline to 2 years. Decreased amounts of minerals often signify bones that are more likely to fracture.

“This milestone achievement will help reduce barriers to developing new treatments that ultimately will improve quality of life for many patients and their families. It represents a fundamental shift in the way clinical studies will be performed in the future,” said Tania Kamphaus, MSc, PhD, associate vice president, Science Partnerships, and director of Patient Engagement at the Foundation for the National Institutes of Health, said in the press release. “It also highlights the critical importance of public-private partnerships to accelerate medical breakthroughs.”

Ashley Lyles is an award-winning medical journalist. She is a graduate of New York University’s Science, Health, and Environmental Reporting Program. Previously, she studied professional writing at Michigan State University. Her work has taken her to Honduras, Cambodia, France, and Ghana and has appeared in outlets such as The New York Times Daily 360, PBS NewsHour, The Huffington Post, Undark, The Root, Psychology Today, Insider, and Tonic (Health by Vice), among other publications.