Independent relationship of osteocalcin circulating levels with obesity, type 2 diabetes, hypertension, and HDL cholesterol

Background: Osteocalcin, a protein synthesized by osteoblasts during the bone formation phase of bone remodeling, is used as a biomarker for the bone production process, and its serum levels are positively correlated with bone mineral density during treatment with anabolic bone drugs for osteoporosis. Higher fat mass has been shown to be a risk factor for osteoporosis and fragility fractures and body fat and bone interplay through several adipokines and bone-derived molecules, regulating bone remodeling, adipogenesis, body weight control, and glucose homeostasis. Aim: The aim of this study was to evaluate the relationship between total osteocalcin levels and obesity, hypertension and type 2 diabetes. Methods: The present study was performed in a cohort of 298 patients including a) 121 overweight and obese patients, unaffected by hypertension or type 2 diabetes, b) 129 subjects affected by hypertension and not by type 2 diabetes, and c) 48 subjects affected by both hypertension and type 2 diabetes. No subject of the group of overweight and obese patients was taking any kind of drug. All patients affected by hypertension, with or without type 2 diabetes, were taking drugs for hypertension. Examining only patients affected by type 2 diabetes (n: 48), 43 (90% of all) were taking drugs to reduce blood glucose levels, 26 (54% of all) were taking drugs to reduce cholesterol levels (statins and/or ezetimide, etc), and 4 (8% of all) were taking ω-3 for hypertriglyceridemia. Each patient was evaluated for anthropometric measurements as well as for serum osteocalcin and uric acid, and plasma glucose, HbA1c, and lipid determination. Results: Osteocalcin levels were significantly and negatively associated with BMI, waist circumference, and HbA1c, and significantly and positively correlated with HDL-cholesterol and systolic blood pressure in the whole population. Osteocalcin levels did maintain an independent negative association with BMI, and HbA1c, and positive association with HDL cholesterol and systolic blood pressure when a multiple regression analyses was performed by considering osteocalcin levels as the dependent variable and BMI, systolic blood pressure, HbA1c, and HDL cholesterol as independent variables. When age was included in the analyses among the independent variables, osteocalcin levels maintained an independent association with BMI, systolic blood pressure, HbA1c, and HDL cholesterol, but not with age. Discussion and Conclusion: The results of the present study seem to suggest that patients with obesity and type 2 diabetes are at higher risk of lower osteocalcin levels and bone formation, whereas higher HDLcholesterol levels and systolic blood pressure seem to be associated to higher osteocalcin production.