Mr Barton is an employee of Procter & Gamble. Dr Felsenberg serves as a consultant for Eli Lilly and Company, GlaxoSmithKline, Merck & Co., Novartis, Nycomed, Procter & Gamble, Roche, and Schering. Dr Watts received honoraria from Aventis, Merck & Co., and Procter & Gamble, serves as a consultant for Aventis, Eli Lilly and Company, GlaxoSmithKline, Merck & Co., Novartis, NPS Pharmaceuticals, Procter & Gamble, Roche, Servier, and Wyeth, and receives funding through his university from Amgen, Aventis, Eli Lilly and Company, Merck & Co., Novartis, and Procter & Gamble. All other authors have no conflict of interest.
Relationship Between Changes in BMD and Nonvertebral Fracture Incidence Associated With Risedronate: Reduction in Risk of Nonvertebral Fracture Is Not Related to Change in BMD†
Version of Record online: 8 AUG 2005
Copyright © 2005 ASBMR
Journal of Bone and Mineral Research
Volume 20, Issue 12, pages 2097–2104, December 2005
How to Cite
Watts, N. B., Geusens, P., Barton, I. P. and Felsenberg, D. (2005), Relationship Between Changes in BMD and Nonvertebral Fracture Incidence Associated With Risedronate: Reduction in Risk of Nonvertebral Fracture Is Not Related to Change in BMD. J Bone Miner Res, 20: 2097–2104. doi: 10.1359/JBMR.050814
- Issue online: 4 DEC 2009
- Version of Record online: 8 AUG 2005
- Manuscript Accepted: 4 AUG 2005
- Manuscript Revised: 25 JUL 2005
- Manuscript Received: 15 FEB 2005
- bone mass;
- nonvertebral fractures;
- surrogate measure;
Whether greater treatment-related changes in BMD result in greater decreases in fracture risk is controversial. We analyzed the relationship between BMD change and nonvertebral fracture risk in postmenopausal osteoporotic women from the risedronate fracture program. Change in BMD did not influence the magnitude of risedronate's effect on nonvertebral fractures; the incidence of nonvertebral fractures was equally low in treated patients whose BMD increased or decreased.
Introduction: In untreated patients, low BMD correlates with increased fracture risk. Whether greater increases in BMD induced by anti-osteoporosis drugs are related to greater decreases in vertebral fracture risk is controversial, and little has been written about the relationship between change in BMD and nonvertebral fracture risk. We analyzed the relationship between BMD change and nonvertebral fracture incidence using individual patient data from postmenopausal osteoporotic women receiving antiresorptive treatment with risedronate.
Materials and Methods: This posthoc analysis combined data from three pivotal risedronate fracture endpoint trials. Women received risedronate 2.5 or 5 mg (n = 2561) or placebo (n = 1418) daily for up to 3 years. BMD and nonvertebral fractures confirmed by radiograph (hip, wrist, pelvis, humerus, clavicle, and leg) were assessed periodically over 3 years.
Results: The incidence of nonvertebral fractures in risedronate-treated patients was not different between patients whose spine BMD decreased (7.8%) and those whose spine BMD increased (6.4%; hazard ratio to subgroup of patients who lost BMD [HR], 0.79; 95% CI, 0.50, 1.25) or between those whose femoral neck BMD decreased (7.6%) and those whose femoral neck BMD increased (7.5%; HR, 0.93; 95% CI, 0.68, 1.28). The changes in lumbar spine and femoral neck BMD explained only 12% (95% CI, 2%, 21%; p = 0.014) and 7% (95% CI, 2%, 13%; p = 0.005), respectively, of risedronate's nonvertebral fracture efficacy.
Conclusions: For patients treated with risedronate, changes in BMD as measured by DXA do not predict the degree of reduction in nonvertebral fractures.