Thiazolidinedione Use and Bone Loss in Older Diabetic Adults

Abstract

CONTEXT: Activation of peroxisome proliferator-activated receptor-gamma by thiazolidinediones (TZDs) results in lower bone mass in mice. OBJECTIVE: The objective of the study was to determine whether TZD use is associated with changes in bone mineral density (BMD) in older adults with type 2 diabetes. DESIGN: We analyzed 4-yr follow-up data from the Health, Aging, and Body Composition observational study. SETTING: The study was conducted in a general community. PATIENTS: White and black, physically able men and women, aged 70-79 yr at baseline with diabetes defined by self-report, use of hypoglycemic medication, elevated fasting glucose (>/=126 mg/dl), or elevated 2-h glucose tolerance test (>/=200 mg/dl) participated in the study. MAIN OUTCOME MEASURES: Whole-body, lumbar spine (derived from whole body), and hip BMD were measured by dual-energy x-ray absorptiometry at 2-yr 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 hemoglobin A(1c) 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% confidence interval (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.