Relationship Between Changes in Bone Mineral Density and Vertebral Fracture Risk Associated With Risedronate: Greater Increases in Bone Mineral Density Do Not Relate to Greater Decreases in Fracture Risk

doi:10.1385/JCD:7:3:255

Journal of Clinical Densitometry

Volume 7, Issue 3, Autumn 2004, Pages 255-261

https://doi.org/10.1385/JCD:7:3:255 Get rights and content

Abstract

Low bone mineral density (BMD) is correlated with increased fracture risk. Whether greater BMD increases induced by osteoporosis drugs are related to greater decreases in fracture risk is controversial. We analyzed the relationship between BMD change and fracture risk in postmenopausal osteoporotic women receiving antiresorptive treatment. The analysis combined data from three pivotal risedronate fracture end-point trials. Women received risedronate (n = 2047) or placebo (n = 1177) daily for up to 3 yr. The BMD and vertebral radiographs were assessed periodically during 3 yr. The estimated risk of new vertebral fracture was compared between patients whose BMD increased and those whose BMD decreased. Risedronate-treated patients whose BMD decreased were at a significantly greater risk (p = 0.003) of sustaining a vertebral fracture than patients whose BMD increased. The fracture risk was similar (about 10%) in risedronate-treated patients whose increases in BMD were < 5% (the median change from baseline) and in those whose increases were≥5% (p = 0.453). The changes in lumbar spine BMD explained only 18% (95% confidence interval [CI], 10%, 26%; p < 0.001) of risedronate's vertebral fracture efficacy. Although patients showing an increase in BMD had a lower fracture risk than patients showing a decrease in BMD, greater increases in BMD did not necessarily predict greater decreases in fracture risk.

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Original ArticleRelationship Between Changes in Bone Mineral Density and Vertebral Fracture Risk Associated With Risedronate: Greater Increases in Bone Mineral Density Do Not Relate to Greater Decreases in Fracture Risk

Abstract

Lancet

Lancet

Am J Med

J Clin Epidemiol

Osteoporosis prevention, diagnosis, and therapy

JAMA

Disease Statistics

Adverse outcomes of osteoporotic fractures in the general population

J Bone Miner Res

Pre-existing fractures and bone mass predict vertebral fracture incidence in women

Ann Intern Med

Long-term fracture prediction by bone mineral assessed at different skeletal sites

J Bone Miner Res

Statistical validation of surrogate endpoints: is bone density a valid surrogate for fracture?

J Musculoskel Neuron Interact

Changes in bone density and turnover explain the reductions in incidence of nonvertebral fractures that occur during treatment with antiresorptive agents

J Clin Endocrinol Metab

Antifracture efficacy of antiresorptive agents are related to changes in bone density

J Clin Endocrinol Metab

A method to assess the proportion of treatment effect explained by a surrogate endpoint

Statist Med

Relationships between bone mineral density and incident vertebral fracture risk with raloxifene therapy

J Bone Miner Res

BMD change explains only a fraction of the observed fracture risk reduction in risedronate-treated patients

Osteoporosis Int

Exploring the relationship between surrogates and clinical outcomes: analysis based on individual patient data versus meta-regression on group-level summary statistics

J Biopharm Statist

Original Article
Relationship Between Changes in Bone Mineral Density and Vertebral Fracture Risk Associated With Risedronate: Greater Increases in Bone Mineral Density Do Not Relate to Greater Decreases in Fracture Risk