The University of Southampton
University of Southampton Institutional Repository

Relationship between changes in bone mineral density and fracture risk reduction with antiresorptive drugs: some issues with meta-analyses

Relationship between changes in bone mineral density and fracture risk reduction with antiresorptive drugs: some issues with meta-analyses
Relationship between changes in bone mineral density and fracture risk reduction with antiresorptive drugs: some issues with 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.
0884-0431
330-337
Delmas, P.D.
f1454c14-9506-42f9-a989-bcb82ffbec46
Li, Z.
053c6730-523c-4972-8d8f-689847240685
Cooper, C.
e05f5612-b493-4273-9b71-9e0ce32bdad6
Delmas, P.D.
f1454c14-9506-42f9-a989-bcb82ffbec46
Li, Z.
053c6730-523c-4972-8d8f-689847240685
Cooper, C.
e05f5612-b493-4273-9b71-9e0ce32bdad6

Delmas, P.D., Li, Z. and Cooper, C. (2004) Relationship between changes in bone mineral density and fracture risk reduction with antiresorptive drugs: some issues with meta-analyses. Journal of Bone and Mineral Research, 19 (2), 330-337. (doi:10.1359/JBMR.0301228).

Record type: Article

Abstract

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.

Full text not available from this repository.

More information

Published date: 2004
Additional Information: JBMR

Identifiers

Local EPrints ID: 25401
URI: https://eprints.soton.ac.uk/id/eprint/25401
ISSN: 0884-0431
PURE UUID: d772b0bd-28e0-47b6-9cbd-ec5d91f38e64
ORCID for C. Cooper: ORCID iD orcid.org/0000-0003-3510-0709

Catalogue record

Date deposited: 07 Apr 2006
Last modified: 06 Jun 2018 12:59

Export record

Altmetrics

Download statistics

Downloads from ePrints over the past year. Other digital versions may also be available to download e.g. from the publisher's website.

View more statistics

Atom RSS 1.0 RSS 2.0

Contact ePrints Soton: eprints@soton.ac.uk

ePrints Soton supports OAI 2.0 with a base URL of https://eprints.soton.ac.uk/cgi/oai2

This repository has been built using EPrints software, developed at the University of Southampton, but available to everyone to use.

We use cookies to ensure that we give you the best experience on our website. If you continue without changing your settings, we will assume that you are happy to receive cookies on the University of Southampton website.

×