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Effects of Thiazide Diuretic Therapy on Bone Mass, Fractures, and Falls

Jane A. Cauley, DrPH; Steven R. Cummings, MD; Dana G. Seeley, MS; Dennis Black, PhD; Warren Browner, MD, MPH; Lewis H. Kuller, MD, DrPH; Michael C. Nevitt, PhD, Study of Osteoporotic Fractures Research Group*
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Copyright 2004 by the American College of Physicians

Ann Intern Med. 1993;118(9):666-673. doi:10.7326/0003-4819-118-9-199305010-00002
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Objective: To determine the relation between the use of thiazide diuretics and bone mass, fractures, and falls in older women.

Design: Cross-sectional study of thiazide diuretics, bone mass, and prevalent vertebral deformities; cohort analysis of thiazide diuretics and nonspinal fractures and falls.

Setting: Four clinical centers located in Baltimore, Maryland; Minneapolis, Minnesota; Portland, Oregon; and the Monongahela Valley, Pennsylvania.

Participants: A total of 9704 ambulatory, nonblack women who were 65 years or older.

Measurements: Information on thiazide use, demographic data, medical history, and anthropometric measurements were obtained by questionnaire, interview, and examination. Appendicular bone mass was measured by single-photon absorptiometry. Incident falls and fractures were ascertained every 4 months.

Results: Women using thiazide diuretics for more than 10 years had significantly higher bone mass than women who had never used thiazide diuretics (for example, 0.381 g/cm2 compared with 0.355 g/cm2 for the distal radius [P < 0.001]). Current users of thiazide diuretics had an incidence of falls (relative risk, 1.06; 95% CI, 0.90 to 1.25) that was similar to that of those who had never used these drugs. After adjusting for age, body weight, functional status, total calcium intake, duration of estrogen replacement therapy, and self-reported health status, we found that current users of thiazide diuretics who had taken these drugs for more than 10 years had a risk for nonspinal (relative risk, 0.99; CI, 0.81 to 1.20) and osteoporotic (relative risk, 0.98; CI, 0.79 to 1.22) fractures that was similar to that of women who had never used thiazides; however, thiazide users did have a lower risk for fractures of the hip (relative risk, 0.63; CI, 0.34 to 1.16) and wrist (relative risk, 0.66; CI, 0.40 to 1.08), neither of which was significant.

Conclusions: Thiazide diuretics have no effect on a woman's risk for falling or for experiencing nonspinal fractures. The trend toward a lower risk for hip and wrist fractures is consistent with findings in previous cohort studies but may reflect selection factors for the use of thiazide diuretics. A randomized trial is needed to determine the effect of thiazide diuretics on the incidence of fractures.

From the University of Pittsburgh, Pittsburgh, Pennsylvania; the University of California, San Francisco, California.*Members and participating institutions are listed in the Appendix. For current author addresses, see end of text.


Grahic Jump Location
Figure 1.
Age-specific incidence rate for 2 or more falls by thiazide diuretic use.

White bars denote women who had never used thiazide diuretics; black bars, past users of thiazide diuretics; and gray bars, current users of thiazide diuretics.

Grahic Jump Location




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