The effect of sexual hormone abnormalities on proximal femur bone mineral density in hemodialysis patients and the possible role of RANKL

Abstract

Sexual hormone concentrations are commonly affected in chronic renal failure. The contribution of sex steroids to bone turnover regulation implies that sex steroid's dysfunction may be implicated in the emergence of renal osteodystrophy. This study was conducted to evaluate sex steroids and gonadotrophins in hemodialysis (HD) patients and to investigate their role in bone homeostasis in concert with other hormones and cytokines. Bone mineral density (BMD) at the proximal femur and intact parathyroid hormone (iPTH), osteoprotegerin, soluble receptor activator of NF-kappaB ligand (sRANKL), prolactin, total testosterone, estradiol, follicle-stimulating hormone (FSH), and luteinizing hormone (LH) were measured in serum samples in 42 patients, 21 men and 21 women, on maintenance HD therapy. Possible associations between clinical characteristics, biochemical parameters, and BMD values were investigated. In male HD patients, the testosterone concentration declined significantly with aging, whereas the estradiol level increased with longer duration of HD. Concurrently, testosterone correlated negatively with sRANKL concentrations (r=-0.520, p=0.016). Luteinizing hormone levels in male patients demonstrated statistically significant negative correlations with BMD values of the proximal femur. In the entire cohort of patients, FSH and LH were negatively associated with absolute values of proximal femur BMD. Gonadotrophin and sexual hormone concentrations in HD patients are associated with bone mineral status and consequently their derangements appear to contribute to the development of bone composition abnormalities in different types of renal osteodystrophy. Furthermore, testosterone's association with sRANKL levels in male HD patients suggests that RANKL may mediate the effect of testosterone on bone metabolism in these patients.

Endogenous Testosterone, Endothelial Dysfunction, and Cardiovascular Events in Men with Nondialysis Chronic Kidney Disease

“…It is possible that bone mineral disorders in uremia may override the associations of endogenous testosterone and phosphate observed at a community level. However, testosterone levels have been negatively associated with bone mineral disorders and receptor activator of nuclear factor -B ligand levels in men undergoing hemodialysis (20).…”

Low Serum Testosterone Increases Mortality Risk among Male Dialysis Patients

“…13 Despite the increased prevalence of hypogonadism and its potential consequences, limited data are available on the influence of endogenous testosterone and replacement therapy in CKD patients. 16 However, testosterone abnormalities have recently been linked to disorders in bone composition, 17 to sRANKL levels, 17 and to endothelial dysfunction 18 in CKD patients. In light of the association between low testosterone concentrations and the risk of developing future cardiovascular events recently reported in nonrenal patient groups, 5,19 we evaluated the possible contribution of testosterone levels to the poor prognosis and the elevated CVD risk of male hemodialysis (HD) patients.…”

Hyperparathyroidism in Hemodialyzed Patients – Relation to Melatonin and Reproductive Hormones Before and After Parathyroidectomy

“…In the same time the pivot role of estrogens on bone formation recently has also been underlined (Leder et al, 2003;Riggs et al, 2002). The relative contribution of sex steroids on bone health and turnover remains still unclear, particularly in HD patients with HPT, because gonadal hormones concentrations are usually affected in chronic renal failure (Doumouchtsis et al, 2008(Doumouchtsis et al, , 2009. Cytochrome P450 enzyme aromatase system is a key component converting adrenal and testicular C19 steroids into C18 steroids.…”

“…(Doumouchtsis et al, 2008;GalMoscovici & Sprague, 2007;Gardham et al, 2010;Hamada & Fukagawa, 2009;Moe et al, 2007). Recent studies of androgens on bone physiology and mineral metabolism at cellular level in animal models and humans revealed that androgen steroids influence bone mass, age related bone loss and the occurrence of fractures, especially in elderly men (Ebeling, 1998(Ebeling, , 2010Lindberg et al, 2005;Vanderschueren et al, 2004) Nevertheless, the specific role of androgens in bone metabolism and skeletal maintenance in men and women is still not fully understood.…”

“…Follicle stimulating hormone (FSH) and luteinizing hormone (LH) are suspected to be negatively associated with bone mineral status (Doumouchtsis et al, 2008 (Fujii et al, 1986). Allan et al (2010) demonstrated that FSH has dosedependent anabolic effects on bone via an ovary-dependent mechanism, which is independent of LH activity, and does not involve direct FSH actions on bone cells.…”