Context: The hypothesis that premenopausal women are relatively protected from mineral loss during PPAR-agonist treatment has not been evaluated in clinical studies.

Objective: To investigate the effect of pioglitazone on bone mineral density (BMD) and bone turnover markers in polycystic ovary syndrome (PCOS).

Design: Randomized, placebo-controlled study.

Setting: Outpatient clinic at a university hospital.

Patients: Thirty premenopausal patients with PCOS and fourteen age and weight-matched healthy females.

Interventions: Pioglitazone (30 mg/day) or placebo for 16 weeks.

Main outcome measures: Measurements of BMD [hip (neck, total), lumbar spine (L2-L4)], bone metabolic parameters [alkaline phosphatase (ALP), 25-hydroxyvitamin D (25OHD), C-telopeptide of type I collagen (ICTP), osteocalcin, and parathyroid hormone (PTH)], endocrine profiles (testosterone, estradiol, and insulin), and measurements of body composition (WHR, BMI, and whole body DXA scans).

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 SD 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 25OHD, 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.