Circadian concentrations of free testosterone, selected markers of bone metabolism, osteoprotegerin and its ligand sRANKL in obese postmenopausal women

Abstract

It has been suggested that increased testosterone secretion in postmenopausal obese women might have some protective effect on bone tissue; the association might be significantly influenced by the RANKL/RANK/OPG system. The aim of the study was to determine whether postmenopausal obese women showed any relationship between the pattern of adipose tissue distribution, circadian free testosterone (FT) concentrations and bone metabolism (as assessed based on circadian osteocalcin [OC] and C-terminal telopeptide [CTx] levels), and to establish whether osteoprotegerin (OPG) and receptor activator of nuclear factor-κB ligand (RANKL) might play a role in the relationship. FT, OC, CTx, OPG and soluble RANKL (sRANKL) levels were determined by ELISA in serum samples collected every three hours for 24 hours from 47 postmenopausal women (12 with gynoid obesity [GO], 17 with android obesity [AO], and 18 healthy individuals). Obese women demonstrated an adipose tissue distribution-dependent increase in mean circadian FT levels and a decrease in mean circadian OC, CTx, OPG and sRANKL compared to control participants. In GO subjects, these changes were accompanied by smaller FT amplitudes, suppression of the circadian rhythms of bone markers and OPG, and a shift of sRANKL rhythm acrophase, whereas AO subjects showed a decrease in bone marker amplitudes and suppression of OPG and sRANKL rhythms. In comparison with the controls, significant adipose tissue distribution-dependent changes were found in the correlations between FT and bone markers, FT and OPG, OC and CTx, OPG and sRANKL, CTx and OPG, and CTx and sRANKL. Compared to GO participants, those with AO had higher coefficients of correlations between mean circadian FT and OC as well as between OC and CTx, and lower in the case of FT and sRANKL as well as CTx and OPG and CTx and sRANKL. Postmenopausal obesity results in adipose tissue distribution-dependent alterations in circadian FT levels accompanied by suppression of bone metabolism and a decline in circadian variations of the osteokines under investigation, especially sRANKL. Increased FT secretion in postmenopausal women might exert a protective effect on bone tissue, most likely via a shift in the OPG/RANKL ratio that tilts the balance toward a functional excess of OPG.