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

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. Pioglitazone treatment was followed by reduced BMD [geometric means (−2 to +2 sd)]: lumbar spine 1.140 (0.964–1.348) vs. 1.127 (0.948–1.341) g/cm2 (average decline 1.1%) and femoral neck 0.966 (0.767–1.217) vs. 0.952 (0.760–1.192) g/cm2 (average decline 1.4%), both P < 0.05. Both ALP and PTH decreased significantly during pioglitazone treatment, whereas no significant changes were measured in 25-hydroxyvitamin D, ICTP, osteocalcin, sex hormones, and body composition. Conclusion: Pioglitazone treatment was followed by decreased lumbar and hip BMD and decreased measures of bone turnover in a premenopausal study population relatively protected from bone mineral loss.