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This version published online on April 11, 2006
Journal of Clinical Endocrinology & Metabolism, doi:10.1210/jc.2005-2226
A more recent version of this article appeared on September 1, 2006
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Submitted on October 12, 2005
Accepted on April 4, 2006

Thiazolidinedione (TZD) Use and Bone Loss in Older Diabetic Adults

Ann V. Schwartz PhD*, Deborah E. Sellmeyer MD, Eric Vittinghoff PhD, Lisa Palermo MS, Beata Lecka-Czernik PhD, Kenneth R. Feingold MD, Elsa S. Strotmeyer PhD, Helaine E. Resnick PhD, MPH, Laura Carbone MD, Brock A. Beamer MD, Seok Won Park MD, PhD, Nancy E. Lane MD, Tamara B. Harris MD, Steven R. Cummings MD, and for the Health, Aging, and Body Composition (Health ABC) Study

Department of Epidemiology and Biostatistics, University of California San Francisco, CA, United States; Division of Endocrinology, Department of Medicine, University of California San Francisco, CA, United States; Reynolds Institute on Aging, Department of Geriatrics, University of Arkansas for Medical Sciences, Little Rock, AR, United States; Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, United States; Department of Epidemiology, MedStar Research Institute, Hyattsville, MD, United States; Division of Rheumatology, Department of Medicine, University of Tennessee, Memphis, TN, United States; Department of Medicine, Johns Hopkins University, Baltimore, MD, United States; Department of Medicine, Pochon CHA University, Korea; Department of Medicine, University of California Davis, Sacramento, CA, United States; Laboratory of Epidemiology, Demography and Biometry, National Institute on Aging, Bethesda, MD, United States; Research Institute, California Pacific Medical Center, San Francisco, CA, United States

* To whom correspondence should be addressed. E-mail: Aschwartz{at}psg.ucsf.edu.

Context: Activation of peroxisome proliferator-activated receptor (PPAR)-{gamma} by thiazolidinediones (TZDs) results in lower bone mass in mice.

Objective: To determine if TZD use is associated with changes in bone mineral density (BMD) in older adults with type 2 diabetes.

Design: We analyzed 4-year follow-up data from the Health, Aging, and Body Composition observational study.

Setting: General community.

Patients: White and black, physically able, men and women, age 70-79 yr at baseline with diabetes, defined by self-report, use of hypoglycemic medication, elevated fasting glucose (≥ 126 mg/dl), or elevated 2-hr glucose tolerance test (≥ 200 mg/dl).

Main Outcome Measures: Whole body, lumbar spine (derived from whole body) and hip BMD were measured by dual energy x-ray absorptiometry at 2-year intervals.

Results: Of 666 diabetic participants, 69 reported TZD use at an annual visit, including troglitazone (n = 22), pioglitazone (n = 30), and/or rosiglitazone (n = 31). Those with TZD use had higher baseline HbA1c and less weight loss over 4 yr but similar baseline BMD and weight than others with diabetes. In repeated measures models adjusted for potential confounders associated with TZD use and BMD, each year of TZD use was associated with greater bone loss at the whole body (additional loss of -0.61% per year; 95% CI: -1.02, -0.21% per year), lumbar spine (-1.23% per year; 95% CI: -2.06, -0.40% per year), and trochanter (-0.65% per year; 95% CI: -1.18, -0.12% per year) in women, but not men, with diabetes.

Conclusion: These observational results suggest that TZDs may cause bone loss in older women. These results need to be tested in a randomized trial.
Key words: Thiazolidinedione • bone density • diabetes mellitus • longitudinal studies




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