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Use of statins and fracture: results of 4 prospective studies and cumulative meta-analysis of observational studies and controlled trials.
Arch Intern Med 2004; 164(2):146-52AI

Abstract

BACKGROUND

The 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) are widely used for the treatment of hyperlipidemia, and recent in vitro and animal data suggest that statins promote bone formation and increase bone strength.

METHODS

To determine whether statin use is associated with a reduced risk for fracture, we analyzed statin use and fracture rates in 4 large prospective studies (the Study of Osteoporotic Fractures, the Fracture Intervention Trial, the Heart and Estrogen/Progestin Replacement Study, and the Rotterdam Study). We searched MEDLINE through January 2002 and abstracts from major scientific meetings and performed a cumulative meta-analysis of published and unpublished observational studies and clinical trials. The meta-analysis included 8 observational studies and 2 clinical trials that reported statin use and documented fracture outcomes.

RESULTS

After adjustment for multiple factors, including age, body mass index, and estrogen use, we found a trend toward fewer hip fractures (relative hazards [RHs], 0.19-0.62) and, to a lesser extent, nonspine fractures (RHs, 0.49-0.95) among statin users in each of the 4 prospective studies. The meta-analysis of observational studies was consistent with these findings. The summary odds ratio (OR) for statin use and hip fracture was 0.43 (95% confidence interval [CI], 0.25-0.75), whereas that for nonspine fracture was 0.69 (95% CI, 0.55-0.88). The meta-analysis of clinical trial results did not support a protective effect with statin use for hip fracture (summary OR, 0.87; 95% CI, 0.48-1.58) or nonspine fracture (OR, 1.02; 95% CI, 0.83-1.26).

CONCLUSIONS

Observational studies suggest that the risk for hip and nonspine fractures is lower among older women taking statin medications for hyperlipidemia, but post hoc analyses of cardiovascular trials do not. Controlled trials specifically designed to test the effect of statins on skeletal metabolism and fracture are needed.

Authors+Show Affiliations

Department of Medicine, University of California, San Francisco 94105, USA. dbauer@psg.ucsf.eduNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Meta-Analysis
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

14744837

Citation

Bauer, Douglas C., et al. "Use of Statins and Fracture: Results of 4 Prospective Studies and Cumulative Meta-analysis of Observational Studies and Controlled Trials." Archives of Internal Medicine, vol. 164, no. 2, 2004, pp. 146-52.
Bauer DC, Mundy GR, Jamal SA, et al. Use of statins and fracture: results of 4 prospective studies and cumulative meta-analysis of observational studies and controlled trials. Arch Intern Med. 2004;164(2):146-52.
Bauer, D. C., Mundy, G. R., Jamal, S. A., Black, D. M., Cauley, J. A., Ensrud, K. E., ... Pols, H. A. (2004). Use of statins and fracture: results of 4 prospective studies and cumulative meta-analysis of observational studies and controlled trials. Archives of Internal Medicine, 164(2), pp. 146-52.
Bauer DC, et al. Use of Statins and Fracture: Results of 4 Prospective Studies and Cumulative Meta-analysis of Observational Studies and Controlled Trials. Arch Intern Med. 2004 Jan 26;164(2):146-52. PubMed PMID: 14744837.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Use of statins and fracture: results of 4 prospective studies and cumulative meta-analysis of observational studies and controlled trials. AU - Bauer,Douglas C, AU - Mundy,Greg R, AU - Jamal,Sophie A, AU - Black,Dennis M, AU - Cauley,Jane A, AU - Ensrud,Kristine E, AU - van der Klift,Marjolein, AU - Pols,Huibert A P, PY - 2004/1/28/pubmed PY - 2004/3/6/medline PY - 2004/1/28/entrez SP - 146 EP - 52 JF - Archives of internal medicine JO - Arch. Intern. Med. VL - 164 IS - 2 N2 - BACKGROUND: The 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) are widely used for the treatment of hyperlipidemia, and recent in vitro and animal data suggest that statins promote bone formation and increase bone strength. METHODS: To determine whether statin use is associated with a reduced risk for fracture, we analyzed statin use and fracture rates in 4 large prospective studies (the Study of Osteoporotic Fractures, the Fracture Intervention Trial, the Heart and Estrogen/Progestin Replacement Study, and the Rotterdam Study). We searched MEDLINE through January 2002 and abstracts from major scientific meetings and performed a cumulative meta-analysis of published and unpublished observational studies and clinical trials. The meta-analysis included 8 observational studies and 2 clinical trials that reported statin use and documented fracture outcomes. RESULTS: After adjustment for multiple factors, including age, body mass index, and estrogen use, we found a trend toward fewer hip fractures (relative hazards [RHs], 0.19-0.62) and, to a lesser extent, nonspine fractures (RHs, 0.49-0.95) among statin users in each of the 4 prospective studies. The meta-analysis of observational studies was consistent with these findings. The summary odds ratio (OR) for statin use and hip fracture was 0.43 (95% confidence interval [CI], 0.25-0.75), whereas that for nonspine fracture was 0.69 (95% CI, 0.55-0.88). The meta-analysis of clinical trial results did not support a protective effect with statin use for hip fracture (summary OR, 0.87; 95% CI, 0.48-1.58) or nonspine fracture (OR, 1.02; 95% CI, 0.83-1.26). CONCLUSIONS: Observational studies suggest that the risk for hip and nonspine fractures is lower among older women taking statin medications for hyperlipidemia, but post hoc analyses of cardiovascular trials do not. Controlled trials specifically designed to test the effect of statins on skeletal metabolism and fracture are needed. SN - 0003-9926 UR - https://www.unboundmedicine.com/medline/citation/14744837/Use_of_statins_and_fracture:_results_of_4_prospective_studies_and_cumulative_meta_analysis_of_observational_studies_and_controlled_trials_ L2 - https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/10.1001/archinte.164.2.146 DB - PRIME DP - Unbound Medicine ER -