Serum osteoprotegerin concentrations are decreased in women with the polycystic ovary syndrome

Abstract

Objective: Osteoprotegerin (OPG), an inhibitor of osteoclastic bone resorption, has a variety of functions including anti-inflammatory effects and a possible cardiovascular protective role. Both low-grade chronic inflammation and cardiovascular risk are increased in women with the polycystic ovary syndrome (PCOS). We aimed to study serum OPG concentrations in PCOS patients. Design: Case-control study including 40 PCOS patients matched with 40 non-hyperandrogenic women for age and body mass index. Methods: Basal serum sampling and standard oral glucose tolerance test, and measurement of serum OPG concentrations by commercial ELISA. Results: Serum OPG concentrations were lower in women with PCOS compared with those of controls (304G120 vs 363G105 pg/ml respectively; FZ7.641, PZ0.007) independently of obesity. No differences were observed in serum receptor activator of nuclear factor-kB ligand (RANKL) levels and in the RANKL/OPG molar ratio. A multivariate linear regression model (R 2 Z0.208, FZ6.579, PZ0.001) showed that PCOS (bZK0.281, PZ0.008), obesity (bZK0.245, PZ0.022) and age (bZ0.296, PZ0.006) were predictive of serum OPG concentrations. Conclusions: Serum OPG concentrations are reduced in PCOS patients independently of obesity. Considering the anti-inflammatory effects of OPG, its reduced serum concentrations might contribute to the proinflammatory state and cardiovascular risk of PCOS patients.European Journal of Endocrinology 159 225-232

Circulating osteoprotegerin and soluble receptor activator of nuclear factor κB ligand in polycystic ovary syndrome: relationships to insulin resistance and endothelial dysfunction

“…Low serum OPG levels were previously reported by Escobar-Morreale et al (24) but in contrast to our findings, the authors failed to detect any association between OPG and glucose metabolism parameters in PCOS women of similar age. It should be pointed out, however, that in our study the HOMA was used, primarily expressing hepatic insulin resistance, whereas in Escobar-Morreale's research, the insulin sensitivity index during oral glucose tolerance test according to Matsuda & DeFronzo was chosen, which rather provides information on whole-body (hepatic and peripheral, in particular muscle) insulin sensitivity.…”

“…Recently, it was shown that serum OPG concentrations are decreased in PCOS and related to hyperandrogenemia (24). However, the relationship of OPG to endothelial injury, one of the initiating events of atherosclerosis, has not been yet described in PCOS.…”

Bone mineral density and vitamin D in PCOS and hirsutism

“…Preserved BMD and the hyperinflammatory state in PCOS could be associated with increased OPG levels. Recent studies, however, reported decreased [53,54] or unchanged [55] OPG levels in PCOS patients versus controls. OPG levels were positively associated with vitamin D, BMD and testosterone, but also with I-CTP, a marker of bone resorption [55].…”

“…OPG levels were positively associated with vitamin D, BMD and testosterone, but also with I-CTP, a marker of bone resorption [55]. In contrast, Pepene and Escobar-Morreale reported inverse associations between OPG, Ferriman-Gallwey score and free testosterone levels in PCOS, but did not measure BMD [54,53]. Intervention studies in hypogonad men [45] and in transsexual women [56] documented significantly increased BMD [45] and increased OPG/RANKL levels [56] after testosterone treatment, thus supporting the positive association between testosterone levels, OPG and BMD.…”

The Polycystic Ovary Syndrome Status - A Risk Factor for Future Cardiovascular Disease

“…Osteoprotegerin (OPG) has both anti-inflammatory and antiapoptotic effects, particularly at the level of endothelial cells, where it exerts a protective role in the development of atherosclerotic plaque and plaque rupture (Scatena and Giachelli, 2002;Schoppert et al, 2002;Kiechl et al, 2007;Kim et al, 2005, as cited in Repaci et al, 2011). Reduced levels of OPG have been observed in obesity and in the presence of insulin resistance (Ugur-Altun et al, 2005;Holecki et al, 2007, as cited in Repaci et al, 2011, as well as in PCOS (Escobar-Morreale et al, 2008), where they were related to the androgen excess (Escobar-Morreale et al, 2008). Interestingly, we have demonstrated very recently that circulating OPG was negatively and significantly correlated with FMD and, moreover, that PCOS women in the upper OPG quartile group (> 2.65 pmol/l) presented significantly altered endothelial function compared to all the rest.…”