Osteocalcin (OC) is an osteoblast-derived peptide circulating in undercarboxylated and γ-carboxylated forms. In mice undercarboxylated osteocalcin (ucOC) modulates insulin secretion and sensitivity, and increases testosterone (T) secretion from Leydig cells. Its relevance to humans is unclear.
We examined cross-sectional associations of ucOC, total OC and other bone turnover markers with diabetes and sex hormones.
Community-dwelling men aged 70-89 years resident in Perth, Western Australia.
Serum total OC, N-terminal propeptide of type I collagen (P1NP) and collagen type I C-terminal cross-linked telopeptide (CTX) were measured by immunoassay, and ucOC by hydroxyapatite binding. T and estradiol (E2) were assayed by mass spectrometry in early morning samples.
There were 2,966 men in the analysis after excluding men with osteoporosis, on bisphosphonates, glucocorticoids or warfarin, and conditions or medications affecting sex hormones. After adjusting for age, smoking, BMI, waist-hip ratio, hypertension, dyslipidemia, creatinine, vitamin D and medical comorbidities, higher ucOC was associated with reduced prevalence of diabetes (odds ratio [OR]=0.55, 95% confidence interval [CI]=0.47-0.64, p<0.001 per 1 SD increase ucOC). Similar results were seen for total OC (OR=0.60, 95% CI=0.50-0.72, p<0.001), P1NP (0.64, 0.54-0.76, p<0.001) and CTX (0.60, 0.52-0.69, p<0.001) but not ucOC/total OC. E2 was inversely associated with ucOC (coefficient -0.04, p=0.031), total OC (-0.05, p=0.001) and CTX (-0.04, p=0.016); and positively with ucOC/total OC (0.05, p=0.002). T was not associated with ucOC, total OC, P1NP, CTX or ucOC/total OC (all p>0.05).
Higher bone remodelling rates are associated with reduced diabetes risk in older men. Although higher ucOC is associated with reduced diabetes risk, it acts as a marker of increased bone remodelling rate, rather than possessing a specific effect. E2, but not T, is inversely associated with bone turnover markers. We found no evidence ucOC, or ucOC/total OC modulates circulating T in men.