Endocrine Abstracts (2008) 16 S30.6

Association of pioglitazone treatment with decreased bone mineral density in obese premenopausal patients with polycystic ovary syndrome: a randomized, placebo-controlled trial

Dorte Glintborg1, Marianne Andersen1, Claus Hagen1, Lene Heickendorff2 & Anne Pernille Hermann1

1Department of Endocrinology and Metabolism, Odense University Hospital, DK-5000 Odense C, Denmark; 2Department of Clinical Biochemistry, Aarhus University Hospital, Nørrebrogade 44, DK-8000 Aarhus C, Denmark.

Background: PPARγ-agonist treatment may decrease bone mineral density (BMD) in postmenopausal women. The hypothesis that premenopausal women are relatively protected from mineral loss during PPARγ-agonist treatment has not been evaluated in clinical studies.

Aim: To investigate the effect of pioglitazone on BMD and bone turnover markers in patients with polycystic ovary syndrome (PCOS).

Methods: Thirty premenopausal PCOS patients were randomized to 16 weeks of pioglitazone (30 mg/day) or placebo treatment. Patients underwent 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). Fourteen age and weight-matched females were included as a control group.

Results: PCOS patients 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 was followed by reduced BMD: 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. ALP and PTH significantly decreased during pioglitazone whereas no significant changes were measured in 25OHD, ICTP, osteocalcin, estradiol, testosterone, 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 against bone mineral loss.

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