Effects of TZD Use and Discontinuation on Fracture Rates in ACCORD Bone Study
Ann V Schwartz1, Haiying Chen1, Walter T Ambrosius1
1University of California (A.V.S., E.V., D.C.B.), San Francisco, California 94143; Wake Forest School of Medicine (H.C., W.T.A., J.D.W.), Winston-Salem, North Carolina 27157; Louis Stokes VA Medical Center and Case Western Reserve University (A.S.), Cleveland, Ohio 44106; St. Michael's Hospital (R.G.J.), Toronto, ON M5B 1W8, Canada; National Heart Lung and Blood Institute (D.E.B.), National Institute of Health, Bethesda, Maryland 20892; Case Western Reserve University (A.M.S.), Cleveland, Ohio 44106; SUNY Downstate Medical Center and Kings County Hospital (M.A.B.), Brooklyn, New York 11203; University of Cincinnati College of Medicine (R.M.C.), Cincinnati, Ohio 45267; VA Medical Center and University of Maryland School of Medicine (B.P.H.), Baltimore, Maryland 21201; University of Miami (T.I.), Miami, Florida 33124; Division of Endocrinology (D.E.S.), Johns Hopkins School of Medicine, Baltimore, Maryland 21205; University of Utah and Salt Lake City Veterans Hospital (D.L.S.), Salt Lake City, Utah 84148; University of Iowa Carver College of Medicine (A.S.-R.), Iowa City, Iowa 52242; and Health Partners Institute for Education and Research (K.M.), Minneapolis, Minnesota 55425.
Context:
In trials, thiazolidinediones (TZDs) increase fracture risk in women, but the effects of discontinuation are unknown.
Objective:
The objective was to investigate the effects of TZD use and discontinuation on fractures in women and men.
Design:
This was a longitudinal observational cohort study using data from the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial bone ancillary study. Duration of TZD use and discontinuation during ACCORD, assessed every 2-4 months at clinic visits, were modeled as time-varying covariates in proportional hazards models for occurrence of first non-spine fracture.
Participants:
We studied a total of 6865 participants in ACCORD BONE.
Main Outcome Measures:
Main outcome measures were centrally adjudicated non-spine fracture.
Results:
Average age was 62.4 (SD, 6.6) years; average duration of diabetes was 11.1 (SD, 7.8) years. Rosiglitazone was used by 74% and pioglitazone by 13% of participants. During a mean follow-up of 4.8 (SD, 1.5) years, 262 men and 287 women experienced at least one non-spine fracture. The fracture rate was higher in women with 1-2 years of TZD use (hazard ratio [HR] = 2.32; 95% confidence interval [CI], 1.49, 3.62) or >2 years of TZD use (HR = 2.01; 95% CI, 1.35, 2.98), compared with no use. The fracture rate was reduced in women who had discontinued TZD use for 1-2 years (HR = 0.57; 95% CI, 0.35, 0.92) or > 2 years (HR = 0.42; 95% CI, 0.24, 0.74) compared with current users. TZD use and discontinuation were not associated with non-spine fractures in men.
Conclusions:
TZD use was associated with increased non-spine fractures in women, but not men, with type 2 diabetes. When women discontinued TZD use, the fracture effects were attenuated.
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