TY - JOUR
T1 - Effects of TZD use and discontinuation on fracture rates in ACCORD bone study
AU - Schwartz, Ann V.
AU - Chen, Haiying
AU - Ambrosius, Walter T.
AU - Sood, Ajay
AU - Josse, Robert G.
AU - Bonds, Denise E.
AU - Schnall, Adrian M.
AU - Vittinghoff, Eric
AU - Bauer, Douglas C.
AU - Banerji, Mary Ann
AU - Cohen, Robert M.
AU - Hamilton, Bruce P.
AU - Isakova, Tamara
AU - Sellmeyer, Deborah E.
AU - Simmons, Debra L.
AU - Shibli-Rahhal, Amal
AU - Williamson, Jeff D.
AU - Margolis, Karen L.
PY - 2015/11/1
Y1 - 2015/11/1
N2 - 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 timevarying 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.
AB - 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 timevarying 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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U2 - 10.1210/jc.2015-1215
DO - 10.1210/jc.2015-1215
M3 - Article
C2 - 26305617
AN - SCOPUS:84958640485
VL - 100
SP - 4059
EP - 4066
JO - Journal of Clinical Endocrinology and Metabolism
JF - Journal of Clinical Endocrinology and Metabolism
SN - 0021-972X
IS - 11
ER -