Thiazolidinedione use and bone loss in older diabetic adults

J Clin Endocrinol Metab. 2006 Sep;91(9):3349-54. doi: 10.1210/jc.2005-2226. Epub 2006 Apr 11.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Absorptiometry, Photon
  • Aged
  • Blood Glucose / metabolism
  • Body Weight
  • Bone Density / drug effects*
  • Bone Density / physiology
  • Cohort Studies
  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Diabetes Mellitus, Type 2 / metabolism
  • Female
  • Glycated Hemoglobin / metabolism
  • Humans
  • Hypoglycemic Agents / adverse effects*
  • Hypoglycemic Agents / therapeutic use*
  • Linear Models
  • Male
  • Osteoporosis / chemically induced
  • Prospective Studies
  • Thiazolidinediones / adverse effects*
  • Thiazolidinediones / therapeutic use*


  • Blood Glucose
  • Glycated Hemoglobin A
  • Hypoglycemic Agents
  • Thiazolidinediones
  • 2,4-thiazolidinedione