On Dec 19, 2025, the US Food and Drug Administration (FDA) announced a major milestone by qualifying total hip bone mineral density (BMD), assessed by dual-energy X-ray absorptiometry, as a surrogate endpoint for fractures in phase 3 trials of investigational drugs in postmenopausal women with osteoporosis. The qualification was based on data generated by the Study to Advance Bone Mineral Density as a Regulatory Endpoint (SABRE)—a public–private partnership funded by the Foundation for the National Institutes of Health (FNIH)—initiated and managed by the FNIH Biomarkers Consortium. SABRE analysed data from 52 clinical trials of osteoporosis drugs (both antiresorptive and anabolic agents) involving more than 160 000 participants, demonstrating that the percentage change in total hip BMD over 2 years was predictive of treatment-related declines in vertebral, non-vertebral, hip, all clinical, and all fractures. By qualifying a surrogate endpoint for osteoporosis trials, the FDA decision is set to transform the field, enabling smaller trials of shorter duration to be conducted, stimulating investment in and accelerating osteoporosis drug development, hastening regulatory approval, and increasing patient access to new treatments with potentially improved safety and efficacy.

The need for new therapies for osteoporosis could not be more urgent. Osteoporosis is an important age-related disease estimated to affect 500 million men and women worldwide. One in three women and one in five men older than 50 years will experience an osteoporotic fracture in their lifetime. As populations age, the burden is set to increase, with rates of some fractures (such as hip fracture) projected to triple by 2050 from levels in 1990. Osteoporotic fractures have serious consequences for individuals, compounded by the fact that a previous fracture increases the risk of future fractures. Fractures are associated with chronic pain, disability, loss of independence, and increased mortality. They also impose a substantial burden on health-care systems. In 2020, osteoporotic fractures accounted for £4·6 billion in direct costs to the UK National Health Service, a figure forecast to rise to £6 billion by 2030. Yet, despite their high incidence and associated costs, osteoporosis and osteoporotic fractures are still underdiagnosed and undertreated. The well documented crisis in osteoporosis—in which patients were either not prescribed available, effective medications or, if prescribed, did not take them due to fear of rare but serious adverse events—has resulted in a persisting major treatment gap.

Development of new osteoporosis medications holds much promise. Safer osteoporosis drugs (devoid of adverse side-effects) would go a long way to rebuild patient confidence and avoid treatment inertia. New, more efficacious anabolic agents might overcome the major limitation of this drug class—ie, that the stimulation of new bone formation wanes within months, thereby limiting increases in BMD.

In a new issue of The Lancet Diabetes & Endocrinology, Benjamin Leder and colleagues report the results of the LIDA trial, which compared 3 months of treatment with romosozumab (the most potent anabolic agent) followed by 9 months of treatment with the antiresorptive denosumab versus 12 months of treatment with romosozumab in postmenopausal women at high risk of fracture. At 12 months, the percentage change in total hip BMD in the 3-month romosozumab group (5·7% [SD 3·3]) was non-inferior to that in the 12-month romosozumab group (6·0% [3·2]). Given the cost of romosozumab, the injection burden, and concerns about potential adverse cardiovascular effects, a shorter treatment course could widen access to this anabolic therapy while helping to allay safety concerns.

The qualification of BMD as a surrogate endpoint in osteoporosis trials is a much needed boost for osteoporosis drug development and bone research more broadly. However, expanding the treatment arsenal for osteoporosis will not be sufficient to close the treatment gap. Greater emphasis must be placed on primary prevention, including treating patients at high risk of osteoporosis (ie, those with osteopenia), particularly young postmenopausal women, and secondary prevention, making greater use of and increasing funding for fracture liaison services. Clearer understanding of and communication around the benefit–risk balance of existing approved medications is essential, as is eliminating disparities in access to diagnosis and treatment.

Finally, the perception of osteoporosis as a disease only affecting women must be challenged to improve awareness, diagnosis, and outcomes in men. The challenges of closing the treatment gap in osteoporosis are immense, but close it we must—musculoskeletal health depends on it.

Source https://www.thelancet.com/journals/landia/home