Thiazide Diuretics and the Risk for Hip Fracture

Thiazide Diuretics and the Risk for Hip Fracture

From Erasmus MC, Rotterdam, the Netherlands; PHARMO Institute, Utrecht, the Netherlands; and Inspectorate for Health Care, The Hague, the Netherlands.

Abstract

Background: Since most hip fractures are related to osteoporosis, treating accelerated bone loss can be an important strategy to prevent hip fractures. Thiazides have been associated with reduced age-related bone loss by decreasing urinary calcium excretion.

Objective: To examine the association between dose and duration of thiazide diuretic use and the risk for hip fracture and to study the consequences of discontinuing use.

Design: Prospective population-based cohort study.

Setting: The Rotterdam Study.

Participants: 7891 individuals 55 years of age and older.

Measurements: Hip fractures were reported by the general practitioners and verified by trained research assistants. Details of all dispensed drugs were available on a day-to-day basis. Exposure to thiazides was divided into 7 mutually exclusive categories: never use, current use for 1 to 42 days, current use for 43 to 365 days, current use for more than 365 days, discontinuation of use since 1 to 60 days, discontinuation of use since 61 to 120 days, and discontinuation of use since more than 120 days.

Results: 281 hip fractures occurred. Relative to nonuse, current use of thiazides for more than 365 days was statistically significantly associated with a lower risk for hip fracture (hazard ratio, 0.46 [95% CI, 0.21 to 0.96]). There was no clear dose dependency. This lower risk disappeared approximately 4 months after thiazide use was discontinued.

Conclusions: Thiazide diuretics protect against hip fracture, but this protective effect disappears within 4 months after use is discontinued.

Article and Author Information

Acknowledgments: The authors thank the people of the Rotterdam Study for participation and the research physicians and assistants of the Rotterdam Study for data collection.
Grant Support: No external funding was obtained for this study.
Potential Financial Conflicts of Interest: None disclosed.
Requests for Single Reprints: Bruno H.Ch. Stricker, MB, PhD, Department of Epidemiology and Biostatistics, Erasmus MC, PO Box 1738, 3000 DR Rotterdam, the Netherlands.
Current Author Addresses: Drs. Schoofs, Hofman, Stijnen, and Stricker: Department of Epidemiology and Biostatistics, Erasmus MC, PO Box 1738, 3000 DR, Rotterdam, the Netherlands.
Drs. van der Klift and Pols: Department of Internal Medicine, Erasmus MC, PO Box 1738, 3000 DR, Rotterdam, the Netherlands.
Dr. de Laet: Department of Public Health, Erasmus MC, PO Box 1738, 3000 DR, Rotterdam, the Netherlands.
Dr. Herings: Prismant, Maliebaan 50, 3581 CS, Utrecht, the Netherlands.
Author Contributions: Conception and design: M.W.C.J. Schoofs, R.M.C. Herings, H.A.P. Pols, B.H.Ch. Stricker.
Analysis and interpretation of the data: M.W.C.J. Schoofs, A. Hofman, T. Stijnen, H.A.P. Pols, B.H.Ch. Stricker.
Drafting of the article: M.W.C.J. Schoofs, R.M.C. Herings, H.A.P. Pols, B.H.Ch. Stricker.
Critical revision of the article for important intellectual content: M. van der Klift, A. Hofman, C.E.D.H. de Laet, R.M.C. Herings, H.A.P. Pols, B.H.Ch. Stricker.
Final approval of the article: M.W.C.J. Schoofs, A. Hofman, H.A.P. Pols, B.H.Ch. Stricker.
Provision of study materials or patients: A. Hofman, H.A.P. Pols.
Statistical expertise: T. Stijnen, B.H.Ch. Stricker.
Obtaining of funding: B.H.Ch. Stricker.
Administrative, technical, or logistic support: H.A.P. Pols, B.H.Ch. Stricker.
Collection and assembly of data: M.W.C.J. Schoofs, M. van der Klift, A. Hofman, C.E.D.H. de Laet, R.M.C. Herings, H.A.P. Pols, B.H.Ch. Stricker.