Thiazolidinedione Use Linked to Increased Fracture Risk in Women
By Laurie Barclay, MD
Medscape Medical News
February 24, 2010 — Thiazolidinedione use is associated with an increased risk for fractures in women, particularly in those older than 65 years, according to the results of a retrospective cohort study reported in the February issue of the Journal of Clinical Endocrinology Metabolism.
"Older women are already at a higher risk of osteoporosis and osteoporosis-related fractures, which might explain why they appeared to be the most affected by TZDs [thiazolidinediones]," senior author L. Keoki Williams, MD, MPH, from the Center for Health Services Research and Department of Internal Medicine at Henry Ford Hospital in Detroit, Michigan, said in a news release. "Fractures are just one of a growing number of problems associated with these medications. Henry Ford and other researchers have previously found that this class of medications also can increase risk of congestive heart failure hospitalization."
The goal of the study was to determine the time-dependent relationship between thiazolidinedione use and fracture risk by comparing patients treated with thiazolidinediones vs those not treated with thiazolidinediones. At a large health system in southeast Michigan, 19,070 patients (9620 women and 9450?men) who received care from the health system were identified. They were at least 18 years old, were diagnosed with diabetes, and had 1 or more prescription for an oral diabetes medication.
The investigators studied the association between exposure and outcomes using Cox proportional hazard models, with the primary outcome being time to fracture. Secondary analyses assessed fracture risk in subgroups based on sex and age.
In the overall cohort, thiazolidinedione use was associated with an increased risk for fracture (adjusted hazard ratio [aHR], 1.35; 95% confidence interval [CI], 1.05 - 1.71]. Thiazolidinedione use was also associated with an increased risk for fracture in women (aHR, 1.57; 95% CI, 1.16 - 2.14) but not in men (aHR, 1.05; 95% CI, 0.70 - 1.58).
Fracture risk was greatest in women older than 65 years (aHR, 1.72; 95% CI, 1.17 - 2.52). Among women, increased fracture risk was not evident until after 1 year of treatment with thiazolidinediones.
"TZDs may put some patients at increased risk for other health issues, and I encourage patients to talk with their physician about other suitable options," Dr. Williams said. "If the physician feels the patient should be placed on a TZD, routine screening for bone loss and prophylactic therapy to prevent bone loss and fractures may also be needed."
Limitations of this study include observational design; reliance on claims data and electronic medical records to identify outcomes; potential misclassification of thiazolidinedione-treated individuals vs those not treated with thiazolidinediones; and lack of data on other important risk factors for fractures, such as body mass index, smoking, diabetic retinopathy and nephropathy, and bone mineral density. Despite the large study size, the numbers of patients and events became much smaller after further stratification, which may have limited power for some of the subanalyses.
"TZD use was associated with an increased risk for fractures in women, particularly at ages above 65 yr," the study authors write. "Clinicians should be aware of this association when considering TZD therapy so as to appropriately manage and counsel their patients."
The Fund for Henry Ford Hospital; the National Heart, Lung, and Blood Institute; and the National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, supported this study. The study authors have disclosed no relevant financial relationships.
