Document Detail

Relationship between changes in bone mineral density and fracture risk reduction with antiresorptive drugs: some issues with meta-analyses.
MedLine Citation:
PMID:  14969404     Owner:  NLM     Status:  MEDLINE    
Published meta-analyses have investigated the relationship between changes in BMD and fracture risk reduction observed with antiresorptive agents, with inconsistent results. Many factors may affect the outcome of such analyses. Our work explores some of these factors and illustrates the need for caution in interpreting the results of meta-analyses. INTRODUCTION: The role of the increase in bone mineral density (BMD) in fracture risk reduction observed in osteoporotic patients treated with antiresorptive drugs is unclear. We examined the effects of study selection, the use of summary statistics or individual patient data (IPD) as the basis for the analyses, and the choice of BMD values used on the outcome of meta-analyses. MATERIALS AND METHODS: To evaluate the effects of study selection, we performed Poisson regression analyses using the results from a number of published studies. To evaluate the effects of using individual patient data instead of summary statistics, we simulated the IPD for vertebral fracture to match the summary statistics for published trials and compared these results with those based on meta-regression using summary statistics. We also evaluated the effect of varying the BMD increase with treatment (3-8%) used in predicting the fracture risk reductions in these simulations. RESULTS: The Poisson regression, which found a statistically significant relationship between nonvertebral fracture risk and spinal BMD when 18 trials of varying designs, duration, and sample size were included in the analysis (p = 0.02), was no longer significant when the analysis was based on the 7 large studies that were placebo-controlled, at least 3 years in duration (at least 1000 patient-years). Meta-analyses of simulated IPD from 12 trials of six antiresorptive agents gave accurate results regardless of the proportion of vertebral risk reduction assumed to be related to BMD change, whereas meta-regression based on summary statistics always produced an estimate around 50%. When the actual data from two risedronate studies were analyzed, the meta-regression based on summary statistics demonstrated a stronger correlation between BMD change and fracture risk reduction than the results based on the IPD analysis. In predicting the fracture risk reduction, the use of the average BMD gain (3%) observed in all studies in the calculations produced an overall fracture risk reduction very similar to the one observed clinically. In contrast, the use of a large BMD gain (8%) produced a substantially higher estimated fracture risk reduction and resulted in a high proportion of fracture risk reduction being attributed to BMD change. CONCLUSIONS: Many factors may influence the outcome of meta-analyses, and caution should be used in interpreting the results of such analyses when exploring the relationship between BMD changes and fracture risk reduction with antiresorptive therapy of osteoporosis.
P D Delmas; Zhengqing Li; Cyrus Cooper
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Publication Detail:
Type:  Journal Article; Meta-Analysis     Date:  2003-12-16
Journal Detail:
Title:  Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research     Volume:  19     ISSN:  0884-0431     ISO Abbreviation:  J. Bone Miner. Res.     Publication Date:  2004 Feb 
Date Detail:
Created Date:  2004-02-18     Completed Date:  2005-07-28     Revised Date:  2005-11-17    
Medline Journal Info:
Nlm Unique ID:  8610640     Medline TA:  J Bone Miner Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  330-7     Citation Subset:  IM    
INSERM Research Unit 403, Claude Bernard University of Lyon, Lyon, France.
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MeSH Terms
Bone Density*
Bone Resorption / drug therapy*
Fractures, Bone / prevention & control*
Risk Factors
Reg. No./Substance:

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