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ARS Home » Northeast Area » Boston, Massachusetts » Jean Mayer Human Nutrition Research Center On Aging » Research » Publications at this Location » Publication #229376
Title: Association Between Serum Osteocalcin and Markers of Metabolic Phenotype

Author
item PITTAS, ANASTASSIOS - TUFTS MEDICAL CENTER
item HARRIS, SUSAN - JM USDA HNRCA @ TUFTS
item ELIADES, MYRTO - TUFTS MEDICAL CENTER
item Dawson-Hughes, Bess

Submitted to: Journal of Clinical Endocrinology and Metabolism
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 12/2/2008
Publication Date: 12/16/2008
Citation: Pittas, A.G., Harris, S.S., Eliades, M., Dawson-Hughes, B. 2008. Association Between Serum Osteocalcin and Markers of Metabolic Phenotype. Journal of Clinical Endocrinology and Metabolism. 94:827-832.

Interpretive Summary: Several recent animal experiments support a regulatory role of the skeleton on glucose and energy homeostasis, which appears to be mediated by osteocalcin, a compound secreted by osteoblasts, the cells that are initiate the formation of new bone. However, this has never been studied in humans. To address this gap, we examined the association between serum osteocalcin levels and glucose regulation as indicated by fasting plasma glucose and insulin levels in 380 healthy men and women who participated in our randomized, controlled calcium and vitamin D intervention trial. This analysis revealed that subjects with higher osteocalcin levels had lower fasting blood sugar levels, lower fasting insulin levels, and lower amounts of body fat. These findings provide support for an important role in humans of osteocalcin to regulate glucose tolerance and insulin sensitivity, confirming recent findings from animal studies.

Technical Abstract: Osteocalcin has been recently reported to contribute to the regulation of glucose tolerance and insulin secretion and sensitivity in experimental animals; however, the data in humans are sparse. To examine the association between serum osteocalcin concentration and markers of dysmetabolic phenotype using data from a completed clinical trial in adults age 65 and older (mean age 71 years, BMI 26.9 kg/m2). In cross-sectional analyses (baseline data), we estimated the associations of serum osteocalcin and urine N-telopeptide with markers of metabolic phenotype including fasting plasma glucose (FPG) [primary outcome], fasting insulin, insulin sensitivity estimated by homeostasis model assessment-insulin resistance (HOMA-IR), plasma C-reactive protein (hsCRP), interleukin-6 (IL-6) and measures of adiposity (BMI and body fat measured by dual-energy x-ray absorptiometry) [secondary outcomes], after multivariate adjustment for age, sex, BMI, smoking, physical activity and education level. In prospective analysis (placebo arm), we estimated the associations of osteocalcin and N-telopeptide concentrations with change in the primary outcome, FPG, over a 3-year period. In cross-sectional analyses, serum osteocalcin concentration was inversely associated with FPG (p=0.01) fasting insulin (p=0.006), HOMA-IR (p=0.002), hsCRP (p=0.01), IL-6 (p=0.02), BMI (p<0.001) and body fat (p<0.001). When participants were divided into tertiles by serum osteocalcin, mean FPG was 97.1 vs. 104.8 mg/dl in the highest vs. lowest osteocalcin tertile, respectively (p<0.01). In prospective analyses, exposure to higher osteocalcin levels during follow-up was associated with a significantly lower rise in FPG at 3 years. Urine N-telopeptide was not associated with any marker of metabolic phenotype. Serum osteocalcin concentration was inversely associated with markers of metabolic dysfunction including fasting hyperglycemia, insulin resistance and systemic inflammation as well as measures of adiposity, confirming studies in animals. Osteocalcin may contribute to the dysmetabolic phenotype in humans.