Association of Pioglitazone Treatment with Decreased Bone Mineral Density in Obese Premenopausal Patients with Polycystic Ovary Syndrome: A Randomized, Placebo-Controlled Trial

Abstract

Objective: Our objective was to investigate the effect of pioglitazone on bone mineral density (BMD) and bone turnover markers in polycystic ovary syndrome (PCOS). Design and Setting:We conducted a randomized, placebo-controlled study at an outpatient clinic at a university hospital.Patients: Thirty premenopausal patients with PCOS and 14 age-and weight-matched healthy females participated.Interventions: Pioglitazone (30 mg/d) or placebo was given for 16 wk. Main Outcome Measures: Measurements of BMD [hip (neck and total) and lumbar spine (L2-L4)], bone metabolic parameters [alkaline phosphatase (ALP), 25-hydroxyvitamin D, C-telopeptide of type I collagen (ICTP), osteocalcin, and PTH], endocrine profiles (testosterone, estradiol, and insulin), and body composition (waist to hip ratio, body mass index, and whole-body dual-energy x-ray absorptiometry scans) were performed. Results:Patients with PCOS had significantly higher levels of ICTP, fasting insulin, and testosterone than controls, whereas no differences were measured in ALP, PTH, body composition, or BMD.

The effect of thiazolidinediones on bone mineral density and bone turnover: systematic review and meta-analysis

“…Of the 11 studies reporting on PINP, three reported significant increases with TZDs [12,18,33], two showed significant decreases [27,31] and six found no effect [13-15, 17, 25, 28]. Of the six studies that reported on osteocalcin, one demonstrated a significant decrease with TZDs [14] and five showed no effect [21,23,25,28,31]. Inclusion of the results of an open-label RCT [20] in a sensitivity analysis did not alter our findings.…”

“…In addition to being heterogeneous, changes in bone turnover markers did not correspond with the observed changes in BMD in this meta-analysis. Furthermore, several included studies that assessed both turnover markers and BMD did not observe a correlation between the two [12,13,23,29]. This is not surprising as the assessment of turnover marker concentrations is associated with considerable within-patient variability [41] and they do not always correspond with small changes in BMD [44].…”

“…Where data were presented in figures, we used digital calipers to extract the data. For studies that presented absolute data rather than percentage change from baseline [13,16,[20][21][22][23], we calculated the mean percentage change from the raw data and calculated the SD of the percentage change using the approaches described in the Cochrane review handbook [24]. Data were pooled using random effects meta-analysis and heterogeneity was assessed using the I 2 statistic (I 2 >50% was considered significant heterogeneity).…”

“…Bray et al (2013) [26] a Bone et al (2013) [25] Henriksen et al (2011) [29] Harris et al (2011) [27] Borges et al (2011) [13] Tungsiripat et al (2010) [32] Grey et al (2007) [14] Total Maalouf et al (2014) [30] Grey et al (2014) [15] Bone et al (2013) [25] Bilezikian et al (2013) [12] Harslof et al (2011) [28] Borges et al (2011) [13] Kanazawa et al (2010) [21] Schindler et al (2009) [22] Glintborg et al (2008) [23] Grey et al (2007) [14] Total Maalouf et al (2014) [30] Grey et al (2014) [15] Bone et al (2013) [25] Bilezikian et al (2013) [12] Harslof et al (2011) [28] Borges et al (2011) [13] Schindler et al (2009) [22] Glintborg et al (2008) [23] Grey et al (2007) [14] Total Acknowledgements We would like to thank the following authors of the included studies for providing us with additional information to facilitate our analyses: G. Duality of interest AG is a shareholder in Auckland Bone Density, which provides bone density measurements. All other authors declare that there is no duality of interest associated with their contribution to this manuscript.…”

Pathophysiological role of enhanced bone marrow adipogenesis in diabetic complications

“…28,29,134,135 Several randomized controlled trials have also examined the involvement of TZDs in skeletal quality. 128,[136][137][138] Most of these studies found essentially no changes in indicators of bone resorption, with a 10-20% decrease in markers associated with osteoblast function and a reduced quantity of osteoblastic precursors. This translated into a significant reduction in bone density in the experimental groups administered TZDs.…”