Plasma osteoprotegerin is associated with testosterone levels but unaffected by pioglitazone treatment in patients with polycystic ovary syndrome.

OBJECTIVE: Increased osteoprotegerin (OPG) levels are associated with increased cardiovascular risk and decreased bone resorption. Pioglitazone treatment reduces the inflammatory state but may decrease bone mineral density (BMD). OPG levels during pioglitazone treatment have not previously been evaluated in polycystic ovary syndrome (PCOS). RESEARCH DESIGN AND METHODS: Plasma OPG levels were measured in 30 PCOS patients before and after randomized treatment with 30 mg pioglitazone/placebo for 16 weeks. Fourteen age- and body mass index-matched healthy women were included as controls. Clinical and hormonal evaluations and whole body dual-energy X-ray absorptiometry scans were performed in all participants. RESULTS: OPG levels were comparable in PCOS patients [12.0 (10.5-14.6) ng/ml] and controls [12.9 (11.7-14.9) ng/ml]. In PCOS patients (no.=30), OPG levels were positively associated with testosterone (r=0.43), PRL (r=0.47), Pyridinoline cross-linked carboxyterminal telopeptide of type I collagen (r=0.43), and hip BMD, whereas inverse associations were found between OPG levels and triglyceride (r=-0.49) and free fatty acid levels during euglycemic clamps (r=-0.38), all p<0.05. Pioglitazone treatment significantly decreased inflammatory markers, insulin sensitivity, and BMD without affecting OPG levels. CONCLUSIONS: OPG levels were comparable in PCOS patients and controls and unchanged during insulin sensitizing treatment with pioglitazone. OPG levels were associated with BMD in PCOS. Future studies need to evaluate OPG as a marker of cardiovascular disease in PCOS.