Osteocalcin and the pituitary-gonadal axis in older men: a population-based study.
OBJECTIVE
Osteocalcin is a well-known marker of bone formation. Recently, mice lacking osteocalcin or its receptor were reported to be subfertile with low testosterone and high luteinizing hormone concentrations. In parallel, in humans, a loss-of-function mutation of the osteocalcin receptor was associated with hypergonadotropic hypogonadism. This suggests that osteocalcin is necessary for normal pituitary-gonadal axis function. Our objective was to determine the association between physiological variations in osteocalcin and the pituitary-gonadal axis in older men.


METHODS
Data were used from the Longitudinal Aging Study Amsterdam (LASA), an ongoing cohort study in a representative sample of the older Dutch population (65-88 years).


METHODS
Serum levels of total (T), free (FT) and bioavailable (bioT) testosterone, luteinizing hormone (LH) and osteocalcin were determined. Data were analysed using linear regression analyses and adjusted for age, BMI, 25-hydroxyvitamin D, parathyroid hormone and vitamin K antagonist use.


RESULTS
A total of 614 men participated in the study. The median age was 75·4 (69·8-81·2) years, and the median osteocalcin level was 1·8 (1·3-2·4) nmol/l. Serum osteocalcin was inversely associated with FT (adjusted B = -0·22 ± 0·09 ng/dl, P = 0·012) and bioT (adjusted B = -0·26 ± 0·08 nmol/l, P < 0·01), but not with total T. Furthermore, osteocalcin was positively associated with LH (adjusted B = 0·09 ± 0·03 U/l, P < 0·01).


CONCLUSIONS
Serum osteocalcin was negatively associated with free and bioavailable testosterone and positively with luteinizing hormone levels.
Department of Endocrinology and Metabolism, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
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Limonard
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van Schoor
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de Jongh
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Lips
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D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000097:blood; D015992:Body Mass Index; D006801:Humans; D007006:Hypogonadism / Q000235:genetics; D008137:Longitudinal Studies; D007986:Luteinizing Hormone / Q000097:blood; D008297:Male; D009154:Mutation; D009426:Netherlands; D015675:Osteocalcin / Q000097:blood*; D010902:Pituitary Gland / Q000502:physiology*; D013739:Testosterone / Q000097:blood
D015415:Biomarkers; D015675:Osteocalcin; D013739:Testosterone; D007986:Luteinizing Hormone