The SABRE Project

Osteoporosis and the fractures it causes represent a growing public health crisis. These fractures are associated with substantial morbidity and increased mortality, affecting an estimated one in two women and one in five men over the age of 50 during their remaining lifetime. While several FDA-approved therapies reduce fracture risk, important gaps remain—particularly for hip and non-vertebral fractures. In addition, concerns about rare but serious side effects limit both patient and clinician willingness to use some existing treatments. As a result, there is an urgent need for new osteoporosis therapies with improved safety, efficacy, and convenience to expand treatment options and improve outcomes.

Progress in osteoporosis drug development has been constrained by the design of traditional clinical trials. Regulatory approval has historically relied on randomized trials using vertebral and non-vertebral fractures as primary endpoints, requiring large sample sizes and long durations—often two to five years. As effective therapies have become available, placebo-controlled trials in high-risk patients are no longer ethical, further increasing trial size and complexity. Recent Phase 3 trials have required enrollment of more than 16,000 participants followed for five years, dramatically increasing development costs and timelines and discouraging innovation in the field.

To address these challenges, the Foundation for the National Institutes of Health (FNIH) Biomarkers Consortium launched the Bone Quality Project in 2013, now known as the FNIH-ASBMR Study to Advance BMD as a Regulatory Endpoint (SABRE) Project. This public-private partnership assembled an unprecedented database of individual patient-level data from over 150,000 participants across 52 randomized controlled trials conducted by both industry and academic investigators. The goal of the project is to identify and qualify a biomarker that can serve as a surrogate endpoint for fractures in osteoporosis clinical trials.

Bone mineral density (BMD), measured by dual-energy X-ray absorptiometry (DXA), is a well-established tool in osteoporosis care and research. Among BMD measures, percentage change in total hip BMD offers several advantages as a surrogate endpoint: excellent measurement precision, minimal interference from age-related degenerative changes, and a strong, consistent association between treatment-related BMD increases and fracture risk reduction.

By qualifying change in total hip BMD as a surrogate endpoint for fractures, this work aims to enable smaller, shorter, and more efficient clinical trials. This approach has the potential to accelerate the development of new osteoporosis therapies and, ultimately, to reduce the significant burden of fractures on patients, families, and the healthcare system. The ultimate aim is to develop a surrogate biomarker endpoint for fracture in clinical trials.