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Relationship between bone mineral density changes with denosumab treatment and risk reduction for vertebral and nonvertebral fractures.

  • Author(s): Austin, Matthew
  • Yang, Yu-Ching
  • Vittinghoff, Eric
  • Adami, Silvano
  • Boonen, Steven
  • Bauer, Douglas
  • Bianchi, Gerolamo
  • Bolognese, Michael
  • Christiansen, Claus
  • Eastell, Richard
  • Grauer, Andreas
  • Hawkins, Federico
  • Kendler, David
  • Oliveri, Beatriz
  • McClung, Michael
  • Reid, Ian
  • Siris, Ethel
  • Zanchetta, Jose
  • Zerbini, Cristiano
  • Libanati, Cesar
  • Cummings, Steven
  • et al.

Published Web Location

https://doi.org/10.1002/jbmr.1472
Abstract

Dual-energy X-ray absorptiometric bone mineral density (DXA BMD) is a strong predictor of fracture risk in untreated patients. However, previous patient-level studies suggest that BMD changes explain little of the fracture risk reduction observed with osteoporosis treatment. We investigated the relevance of DXA BMD changes as a predictor for fracture risk reduction using data from the FREEDOM trial, which randomly assigned placebo or denosumab 60 mg every 6 months to 7808 women aged 60 to 90 years with a spine or total hip BMD T-score < -2.5 and not < -4.0. We took a standard approach to estimate the percent of treatment effect explained using percent changes in BMD at a single visit (months 12, 24, or 36). We also applied a novel approach using estimated percent changes in BMD from baseline at the time of fracture occurrence (time-dependent models). Denosumab significantly increased total hip BMD by 3.2%, 4.4%, and 5.0% at 12, 24, and 36 months, respectively. Denosumab decreased the risk of new vertebral fractures by 68% (p < 0.0001) and nonvertebral fracture by 20% (p = 0.01) over 36 months. Regardless of the method used, the change in total hip BMD explained a considerable proportion of the effect of denosumab in reducing new or worsening vertebral fracture risk (35% [95% confidence interval (CI): 20%-61%] and 51% [95% CI: 39%-66%] accounted for by percent change at month 36 and change in time-dependent BMD, respectively) and explained a considerable amount of the reduction in nonvertebral fracture risk (87% [95% CI: 35% - >100%] and 72% [95% CI: 24% - >100%], respectively). Previous patient-level studies may have underestimated the strength of the relationship between BMD change and the effect of treatment on fracture risk or this relationship may be unique to denosumab.

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