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

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, E2 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, E2 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.