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

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Watts, Nelson B.¹; Geusens, Piet²; Barton, Ian P.³; Felsenberg, Dieter⁴

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. December 2005;20(12):2097-2104

©2005 American Society for Bone and Mineral Research

Affiliations

¹University of Cincinnati Bone Health and Osteoporosis Center, Cincinnati Ohio, USA

²Limburgs Universitair Centrum, Diepenbeek, Belgium and Department of Rheumatology, University Hospital, Maastricht, The Netherlands

³Procter & Gamble Pharmaceuticals, Mason, Ohio, USA

⁴Free University Berlin, University Hospital Benjamin Franklin, Centre of Muscle and Bone Research, Berlin, Germany
Abstract and keywords

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.

Keywords: bone mass; nonvertebral fractures; risedronate; surrogate measure; osteoporosis
Links

DOI: 10.1359/JBMR.050814

PubMed: 16294263

WoS: 000233517700004
History

Received: 2005-02-15

Revised: 2005-07-25

Accepted: 2005-08-04

Online: 2005-08-08

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