Effects of pioglitazone on bone in postmenopausal women with impaired fasting glucose or impaired glucose tolerance: a randomized, double-blind, placebo-controlled study - PubMed (original) (raw)
Randomized Controlled Trial
. 2013 Dec;98(12):4691-701.
doi: 10.1210/jc.2012-4096. Epub 2013 Sep 20.
Affiliations
- PMID: 24057294
- DOI: 10.1210/jc.2012-4096
Randomized Controlled Trial
Effects of pioglitazone on bone in postmenopausal women with impaired fasting glucose or impaired glucose tolerance: a randomized, double-blind, placebo-controlled study
Henry G Bone et al. J Clin Endocrinol Metab. 2013 Dec.
Abstract
Context: Meta-analyses of clinical studies have suggested an increased incidence of peripheral fractures in postmenopausal women with type 2 diabetes mellitus taking pioglitazone. The mechanism behind this apparent increase is unknown.
Objective: The objective of the study was to examine the effects of pioglitazone on bone mineral density (BMD) and turnover.
Design and setting: Twenty-five sites (in the United States) enrolled participants in this randomized, double-blind, placebo-controlled study.
Participants: Postmenopausal women (n = 156) with impaired fasting glucose or impaired glucose tolerance participated in the study.
Interventions: The intervention consisted of pioglitazone 30 mg/d (n = 78) or placebo (n = 78), increased to 45 mg/d after 1 month, for 12 months of treatment total, followed by 6 months of washout/follow-up.
Main outcome measures: Percentage changes from baseline to month 12 and from month 12 to month18 in BMD in total proximal femur (primary end point), total body, femoral neck, lumbar spine, and radius were measured.
Results: Least squares mean changes from baseline to month 12 in total proximal femur BMD were -0.69% for pioglitazone and -0.14% for placebo (P = .170). No statistically significant between-group differences were observed for any BMD or bone remodeling marker end point. We observed improved glycemic control and insulin sensitivity with pioglitazone treatment. In addition, pioglitazone appeared to increase body fat, which may affect bone density measurements, especially in the lumbar spine. One pioglitazone-treated and three placebo-treated women experienced confirmed fractures. Over 18 months, one pioglitazone-treated (1.3%) and eight placebo-treated women (10.3%) developed overt type 2 diabetes mellitus. The pattern and incidence of adverse events with pioglitazone were consistent with clinical experience with thiazolidinediones.
Conclusions: Maximal-dose pioglitazone had no effects on BMD or bone turnover, while improving glycemic control as expected, in postmenopausal women with impaired fasting glucose or impaired glucose tolerance.
Trial registration: ClinicalTrials.gov NCT00708175.
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