Effects of estrogen-progestin therapy on serum levels of RANKL, osteoprotegerin, osteocalcin, leptin, and ghrelin in postmenopausal women.

OBJECTIVE: The aim of this study was to evaluate the effects of estrogen-progestin therapy on serum levels of receptor-activating nuclear factor kappabeta ligand (RANKL), osteoprotegerin, osteocalcin, leptin, and ghrelin in a cross-sectional study of 99 healthy postmenopausal women conducted at the Menopause Clinic of our department. DESIGN: In this cross-sectional, observational study, 99 participants were divided into two groups. Group A was composed of 77 postmenopausal women who had never received estrogen-progestin therapy, and group B was composed of 22 postmenopausal women who had received transdermal 17beta-estradiol at a dose of 50 microg/day in a continuous regimen for at least 24 months and nomegestrol at a dose of 5 mg/day for 12 days/month in a sequential regimen. All participants underwent blood sampling in the morning and quantitative ultrasound bone-densitometry measurement of the proximal phalanges of the dominant hand. RESULTS: T score and amplitude-dependent speed of sound were significantly higher in group B than in group A. No significant differences in RANKL, osteoprotegerin, and osteocalcin were observed between the two groups. Serum leptin levels were significantly lower in group B than in group A, whereas ghrelin was significantly higher in group B than in group A. CONCLUSIONS: The data gathered in this preliminary study indicate that estrogen-progestin therapy may protect against postmenopausal bone loss, but this protective effect does not seem to be exerted through action on the RANK-RANKL-osteoprotegerin system. Similarly, although several reports suggest that leptin and ghrelin are involved in bone metabolism, we could not detect any important correlation of these two hormones with bone metabolism or bone status in treated and untreated postmenopausal women. Because of the limited number of treated participants and the study design, the results of this preliminary study must be confirmed in larger, prospective, longitudinal studies.