Effects of TZD use and discontinuation on fracture rates in ACCORD bone study

Ann V. Schwartz, Haiying Chen, Walter T. Ambrosius, Ajay Sood, Robert G. Josse, Denise E. Bonds, Adrian M. Schnall, Eric Vittinghoff, Douglas C. Bauer, Mary Ann Banerji, Robert M. Cohen, Bruce P. Hamilton, Tamara Isakova, Deborah E. Sellmeyer, Debra L. Simmons, Amal Shibli-Rahhal, Jeff D. Williamson, Karen L. Margolis

Research output: Contribution to journalArticle

36 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)4059-4066
Number of pages8
JournalJournal of Clinical Endocrinology and Metabolism
Volume100
Issue number11
DOIs
StatePublished - Nov 1 2015
Externally publishedYes

Fingerprint

Thiazolidinediones
Medical problems
Bone
Bone and Bones
Hazards
Confidence Intervals
rosiglitazone
pioglitazone
Outcome Assessment (Health Care)
Ambulatory Care
Proportional Hazards Models
Type 2 Diabetes Mellitus
Observational Studies
Cohort Studies

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Endocrinology
  • Clinical Biochemistry
  • Biochemistry, medical

Cite this

Schwartz, A. V., Chen, H., Ambrosius, W. T., Sood, A., Josse, R. G., Bonds, D. E., ... Margolis, K. L. (2015). Effects of TZD use and discontinuation on fracture rates in ACCORD bone study. Journal of Clinical Endocrinology and Metabolism, 100(11), 4059-4066. https://doi.org/10.1210/jc.2015-1215

Effects of TZD use and discontinuation on fracture rates in ACCORD bone study. / Schwartz, Ann V.; Chen, Haiying; Ambrosius, Walter T.; Sood, Ajay; Josse, Robert G.; Bonds, Denise E.; Schnall, Adrian M.; Vittinghoff, Eric; Bauer, Douglas C.; Banerji, Mary Ann; Cohen, Robert M.; Hamilton, Bruce P.; Isakova, Tamara; Sellmeyer, Deborah E.; Simmons, Debra L.; Shibli-Rahhal, Amal; Williamson, Jeff D.; Margolis, Karen L.

In: Journal of Clinical Endocrinology and Metabolism, Vol. 100, No. 11, 01.11.2015, p. 4059-4066.

Research output: Contribution to journalArticle

Schwartz, AV, Chen, H, Ambrosius, WT, Sood, A, Josse, RG, Bonds, DE, Schnall, AM, Vittinghoff, E, Bauer, DC, Banerji, MA, Cohen, RM, Hamilton, BP, Isakova, T, Sellmeyer, DE, Simmons, DL, Shibli-Rahhal, A, Williamson, JD & Margolis, KL 2015, 'Effects of TZD use and discontinuation on fracture rates in ACCORD bone study', Journal of Clinical Endocrinology and Metabolism, vol. 100, no. 11, pp. 4059-4066. https://doi.org/10.1210/jc.2015-1215
Schwartz, Ann V. ; Chen, Haiying ; Ambrosius, Walter T. ; Sood, Ajay ; Josse, Robert G. ; Bonds, Denise E. ; Schnall, Adrian M. ; Vittinghoff, Eric ; Bauer, Douglas C. ; Banerji, Mary Ann ; Cohen, Robert M. ; Hamilton, Bruce P. ; Isakova, Tamara ; Sellmeyer, Deborah E. ; Simmons, Debra L. ; Shibli-Rahhal, Amal ; Williamson, Jeff D. ; Margolis, Karen L. / Effects of TZD use and discontinuation on fracture rates in ACCORD bone study. In: Journal of Clinical Endocrinology and Metabolism. 2015 ; Vol. 100, No. 11. pp. 4059-4066.
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abstract = "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.",
author = "Schwartz, {Ann V.} and Haiying Chen and Ambrosius, {Walter T.} and Ajay Sood and Josse, {Robert G.} and Bonds, {Denise E.} and Schnall, {Adrian M.} and Eric Vittinghoff and Bauer, {Douglas C.} and Banerji, {Mary Ann} and Cohen, {Robert M.} and Hamilton, {Bruce P.} and Tamara Isakova and Sellmeyer, {Deborah E.} and Simmons, {Debra L.} and Amal Shibli-Rahhal and Williamson, {Jeff D.} and Margolis, {Karen L.}",
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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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