Osteoporosis therapies reduce fracture risk for women regardless of BMD status
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Osteoporosis therapies work equally well for women at high risk for fracture with high or low bone mineral density, according to data from the virtual American Society for Bone and Mineral Research Annual Meeting.
“For clinicians, it is important to know that for women at high risk for fractures, data suggests that those with T-scores below and above –2.5 would benefit from anti-fracture therapies,” Dennis M. Black, PhD, professor of epidemiology and biostatistics at the University of California, San Francisco, and an adjunct investigator at Kaiser Permanente Southern California, told Healio. “The caveat is they have to be at high risk for fracture because the underlying studies we used in our analysis screen people to be at relatively high risk before entering the trial.”
Study design
Black and colleagues analyzed pooled data from 24 randomized controlled trials with fracture endpoints, using individual patient data compiled in the FNIH-ASBMR SABRE database to determine whether anti-fracture efficacy differs in those with a T-score above or below –2.5. The trials included 95,907 participants with baseline femoral neck BMD measurements and assessed bisphosphonates (n = 13), odanacatib (n = 1), hormone therapy (n = 2) parathyroid hormone analogs (n = 3), denosumab (Prolia, Amgen; n = 1) and selective estrogen receptor modulators (n = 4). Mean age across trials was 71 years with 39% having a previous vertebral fracture; mean baseline femoral neck T-score was –2.2. Researchers stratified participants by femoral neck T-scores of less than –2.5 (n = 37,149) and at least –2.5 (n = 58,488) and by fracture type (vertebral, non-spine, hip and all clinical). Researchers used Cox proportional hazard models or logistic regression to compare fracture risk reduction among BMD subgroups.
Researchers found that fracture risk was reduced across the four fracture types in both BMD subgroups. Risk ratio for vertebral fracture for those treated compared with those assigned placebo was 0.56 for those with a baseline T-score greater than –2.5 and 0.51 for those with a baseline T-score below –2.5 (P = .006). Black also noted that the number needed to treat for all three fracture types was consistently lower among women with a femoral neck T-score less than –2.5, due to higher risk and larger risk reductions.
“In general, osteoporosis drugs work equally well for those with high or low BMD, but that is not to say everyone should be treated,” Black said.
BMD as surrogate endpoint
The findings are part of a larger project to develop surrogate endpoints for osteoporosis drug trials, Black said in an interview after his presentation.
“For many reasons, those trials have gotten really large — 15,000 women over 5 years,” Black said. “They are so big that people are not developing drugs anymore. What we are trying to do is identify a surrogate endpoint instead of fractures. What we are proposing is instead of fracture, assess a change in BMD over 2 years. It is much simpler, much smaller and much quicker.”
Black said the results suggest it makes sense to include women with a high BMD in trials for osteoporosis therapies.
“The answer is yes, it did make sense,” Black said. “Whether women had low or high BMD, the reductions [in risk] after treatment were similar. This could be modeled after surrogate endpoints in diabetes trials. We think this [endpoint] is better because BMD really is on the causal pathway. That is where this data fits into the bigger picture.”
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Black DM, et al. Do women with lower BMD benefit more from anti-fracture treatment? An analysis pooling individual patient data from 96,000 people in the FNIH-SABRE RCT database. Presented at: American Society for Bone and Mineral Research Annual Meeting; Sept. 11-15, 2020 (virtual meeting).
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