Circulating osteoprotegerin and soluble receptor activator of nuclear factor κB ligand in polycystic ovary syndrome: relationships to insulin resistance and endothelial dysfunction.
OBJECTIVE
There is plenty of evidence that osteoprotegerin (OPG) is linked to subclinical vascular damage and predicts cardiovascular disease in high-risk populations. Our aim is to investigate the relationships of OPG/free soluble receptor activator of nuclear factor κB ligand (sRANKL) to insulin resistance, brachial artery flow-mediated vasodilation (FMD), and the carotid artery intima-media thickness (CIMT) in polycystic ovary syndrome (PCOS), a disorder characterized by hyperandrogenism, impaired glucose control, and endothelial injury.


METHODS
A cross-sectional, observational study.


METHODS
Hormonal and metabolic profiles, FMD, CIMT, serum OPG, and ampli-sRANKL were assessed in 64 young PCOS patients and 20 controls of similar age. Body composition was measured by dual energy X-ray absorptiometry.


RESULTS
OPG was significantly lower in PCOS and related negatively to free testosterone and positively to estradiol (E(2)) levels. In multivariate analysis, OPG but not ampli-sRANKL correlated positively to fasting insulin, insulin sensitivity indices, and FMD. Neither OPG nor ampli-sRANKL was associated with CIMT. Significantly lower adjusted FMD values were demonstrated in women in the upper OPG quartile group (>2.65 pmol/l) compared with all other quartile groups together (P=0.012). In PCOS, multiple regression analysis retained E(2)/sex hormone-binding globulin ratio, fat mass, and homeostasis model assessment of insulin resistance as independent predictors of OPG.


CONCLUSIONS
In PCOS, circulating OPG is related to both endothelial dysfunction and insulin resistance, independent of obesity and androgen excess, suggesting OPG as a useful biomarker of these effects. Further studies are needed to evaluate OPG in relation to cardiovascular events and cardiovascular mortality in PCOS.
Departments of Endocrinology Internal Medicine-Cardiology, University of Medicine and Pharmacy Cluj-Napoca, 3-5 Louis Pasteur, 400349 Cluj-Napoca, Romania. c_e_georgescu@yahoo.com
Carmen Emanuela
CE
Pepene
Ioana Rada
IR
Ilie
Ioan
I
Marian
Ileana
I
Duncea
D000328:Adult; D015415:Biomarkers / Q000097:blood; D001783:Blood Flow Velocity; D001823:Body Composition; D001916:Brachial Artery / Q000503:physiopathology; D002339:Carotid Arteries / Q000473:pathology; D003430:Cross-Sectional Studies; D004730:Endothelium, Vascular / Q000503:physiopathology; D004958:Estradiol / Q000097:blood; D005260:Female; D006801:Humans; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D053244:Osteoprotegerin / Q000097:blood*; D011085:Polycystic Ovary Syndrome / Q000097:blood* / Q000503:physiopathology; D011446:Prospective Studies; D053245:RANK Ligand / Q000097:blood; D053246:Receptor Activator of Nuclear Factor-kappa B / Q000097:blood*; D012044:Regression Analysis; D012738:Sex Hormone-Binding Globulin / Q000378:metabolism; D013739:Testosterone / Q000097:blood; D017539:Tunica Intima / Q000473:pathology; D017540:Tunica Media / Q000473:pathology; D014664:Vasodilation
D015415:Biomarkers; D007328:Insulin; D053244:Osteoprotegerin; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; D012738:Sex Hormone-Binding Globulin; D013739:Testosterone; D004958:Estradiol