Elevated serum receptor activator of nuclear factor kappa B ligand and osteoprotegerin levels in late-onset male hypogonadism

Abstract

Purpose: Studies that analyze the levels of osteoprotegerin (OPG) or receptor activator of nuclear factor kappa B ligand (RANKL) in hypogonadal men, the majority of whom have prostate cancer or are undergoing androgen-deprivation therapy, are few and inconclusive. Methods: 81 men aged 69.3 ± 0.8 years (39 men with late-onset hypogonadism and 42 age-matched controls) were recruited. Serum levels of OPG, total soluble RANKL (sRANKL), total and free testosterone (FT), estradiol (E2), sex hormone-binding globulin (SHBG), follicle-stimulating hormone, luteinizing hormone (LH), prolactin, bone-specific alkaline phosphatase (BAP) and β-Cross Laps were assessed. Results: Compared with controls, both OPG (p = 0.023) and sRANKL (p = 0.010) serum levels were increased in men with late-onset hypogonadism; however, when expressed as a ratio, sRANKL/OPG, the two groups were not significantly different. Simple and age-adjusted analyses showed that OPG was inversely related to FT and positively related to SHBG, E 2 and BAP. In the patient population, LH demonstrated statistically significant correlations with both OPG (r = 0.274, p = 0.013) and sRANKL (r = 0.276, p = 0.018). Multiple regression analysis retained age, SHBG, E 2 and BAP as independent predictors of OPG, explaining 27.71% of serum OPG variability. Conclusions: Late-onset hypogonadism is associated with enhanced RANKL activity. Increased bone turnover-related OPG levels may act as a coupling factor between bone resorption and formation. The results suggest anti-RANKL-agents as therapeutic tools in osteoporotic men with late-onset hypogonadism. © 2011 CIM.