Greater improvements in bone mineral density (BMD) are strongly associated with greater reductions in fracture risk, especially in the vertebrae and hip, according to study results published in the Journal of Bone and Mineral Research.

Available treatments for osteoporosis have been shown to greatly reduce the risk for vertebral fractures, but their effects on hip and nonvertebral fracture risk are less significant. To examine the historically varied association between BMD and reductions in fracture risk and to incorporate data from published literature on newer osteoporosis drugs, researchers conducted a meta-regression of 38 randomized placebo-controlled trials of 19 different therapies for which the number of participants ranged from 246 to >16,000.

Between-group differences (active vs placebo) in BMD change ranged from 1.21% to 6.9% for the total hip, 2.1% to 5.9% for the femoral neck, and 0.73% to 13.3% for the lumbar spine. Risk ratios ranged from 0.14 to 1.03 for vertebral fractures, 0.47 to 1.12 for hip fractures, and 0.37 to 1.58 for nonvertebral fractures.

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The researchers discovered that greater BMD improvements in the total hip, femoral neck, and lumbar spine were associated with a greater reduction in vertebral fracture (r2 =0.56, r2 =0.54, r2 =0.63, respectively; P ≤.0002 for all). As such, a 2% or 6% improvement in total hip BMD might yield a 28% or 66% reduction in vertebral fracture risk, for example.

Likewise for hip fracture, the r2 values for total hip, femoral neck, and lumbar spine were 0.48 (P =.01), 0.42 (P =.02), and 0.22 (not significant), respectively. As such, a 2% or 6% improvement in total hip BMD might yield a 16% or 40% reduction in hip fracture risk.

In several sensitivity analyses, which excluded trials that lasted <2 years, associations were found to be slightly stronger between changes in hip BMD and reduction in vertebral fracture.

Several limitations were noted for this study, including that reviewed trials that lasted only 1 year might have underestimated long-term effects of treatment.

“[L]arger improvements in [dual-energy X-ray absorptiometry]-based BMD are associated with greater reductions in fracture risk, particularly for vertebral and hip fractures,” the researchers said, adding that their results “provide compelling evidence that improvements in BMD with osteoporosis therapies may be useful as surrogate endpoints for fracture in trials of new therapeutic agents.”


Bouxsein ML, Eastell R, Lui L, et al. Change in bone density and reduction in fracture risk: a meta-regression of published trials [published online January 23, 2019]. J Bone Miner Res. doi: 10.1002/jbmr.3641

This article originally appeared on Endocrinology Advisor