BoneKEy Reports | BoneKEy Watch

BMD change predicts bone fracture risk due to zoledronate treatment


Analysis of data from 7736 postmenopausal women participating in the HORIZON-PFT study measured both the annual change in total hip bone mineral density (BMD) and the three-year change, to assess its contribution to fracture risk reduction during treatment with once-yearly intravenous zoledronic acid (5 mg).

The three-year change in BMD contributed 61% (95% CI, 24% to 156%) of the reduction in non-vertebral fracture risk, but the annual change in BMD was not predictive. In contrast, both annual and three-year changes in total hip BMD explained 40% (95% CI, 30% to 54%) of the treatment effect on vertebral fracture risk. The authors conclude that previous studies underestimated the correlation between change in BMD and fracture risk reduction, possibly because of poorer compliance.

The annual change in levels of the bone formation marker procollagen type 1 amino-terminal propeptide also contributed to 58% of the benefit of zoledronic acid in reducing the risk of new vertebral fractures (95% CI, 15% to 222%).

Editor's comment: This analysis follows a similar study looking at denosumab, another potent anti-resorptive drug that was also administered parenterally, maximising compliance. Both studies corroborate preclinical studies, demonstrating that the level and stability of bone turnover suppression correlates with the increase in bone mass and strength achieved, with BMD changes due to bisphosphonate therapy making a greater contribution to fracture risk reduction than expected. In the accompanying editorial, Miller proposes annual BMD as a primary surrogate marker for anti-fracture efficacy.

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