Osteocalcin is associated with testosterone in the general population and selected patients with bone disorders

Abstract

SUMMARYResearch in the last decade has revealed that bone is not only a target tissue for numerous circulating hormones but functions as an endocrine organ itself. As a recent study demonstrated a stimulatory effect of the osteoblast-derived hormone osteocalcin (OCN) on testosterone production in mice, we investigated whether such an association can be replicated in humans. We used data from 1338 men (25-86 years) in the population-based epidemiological Study of Health in Pomerania and from 110 male outpatients with bone disorders (18-85 years) for the study. We analysed cross-sectional associations between OCN and total testosterone serum concentrations (TT), as well as associations between further markers of bone turnover [bone-specific alkaline phosphatase (BAP), serum C-terminal telopeptides of Type I collagen (CTX), urinary deoxypyridinoline] and TT using ordinary least square (OLS) regression models. Multivariable OLS models revealed a positive association between OCN and TT in the population-based (b coefficients for a one standard deviation increase, 0.590; standard error (SE), 0.175; p-value, <0.01) and patient-based (b coefficient, 0.575; SE, 0.132; pvalue, <0.01) samples even after adjustment for age and body mass index (both samples), and time of blood sampling (populationbased sample only). Furthermore, we observed positive associations between BAP and TT (b coefficient, 0.403; SE, 0.170; p-value, 0.02) as well as between CTX and TT (b coefficient, 0.733; SE, 0.172; <0.01) in men from the general population. The present investigation shows that OCN is associated with TT in the general population and in patients with bone disorders, and may thus indicate general male health status. Additional longitudinal observational studies are warranted to confirm our findings and future experimental research is necessary to elucidate potential mechanisms underlying the observed associations.

Associations Between Liver Function, Bone Turnover Biomarkers and Adipokines in Older Patients With Hip Fracture

“…Reported in the literature age and gender-based differences in liver [32,[34][35][36] and bone turnover markers [38][39][40][41][42], as well as in three studied adipokines [43][44][45][46] were confirmed within our study population, specifically, the decrease of transaminase activities and increase of bone turnover (OC and NTx/Cr) with ageing, and higher levels of urinary bone resorption markers and circulating adiponectin and leptin in women than in men.…”

Regulation of male fertility by the bone-derived hormone osteocalcin

“…Testing this hypothesis using loss-of-function and gain-of-function mouse models of bone resorption, it was shown that bone resorption is a physiological determinant of osteocalcin's regulation of testosterone production and male reproductive function through its ability to activate osteocalcin 49 . In addition, it was recently shown in humans that osteocalcin and the bone turnover is associated with testosterone circulating levels in the general population and in patients with bone disorders 40,41 . The data presented so far support a model in which osteoclast-mediated bone resorption regulates male fertility in mice through the decarboxylation and the activation of osteocalcin.…”

Endocrine role of bone: recent and emerging perspectives beyond osteocalcin

“…This conflicting results may be attributable to the lack of a commercially available undercarboxylated assay, or differing methodologies (Ducy 2011). Similarly, it appears that the reproductive function of OC translates to humans, with the identification of a positive association between OC and testosterone serum levels in the general population, patients with bone disorders and patients with T2DM (Hannemann et al 2013, Kanazawa et al 2013. Furthermore, two subjects were identified from a cohort of patients displaying testicular failure who harboured a heterozygous missense variant in one of the transmembrane domains of GPRC6A, giving credence to a role of OC function in humans (Oury et al 2013;reviewed in Karsenty & Oury (2014)).…”