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BACKGROUND: Novel biomarkers of vascular disease in diabetes could help identify new mechanistic pathways. Osteocalcin, osteoprotegerin and osteopontin are key molecules involved in bone and vascular calcification processes, both compromised in diabetes. We aimed to evaluate possible associations of osteocalcin, osteoprotegerin and osteopontin with cardiovascular disease (CVD) and diabetic retinopathy (DR) among people with type 2 diabetes (T2D). MATERIAL AND METHODS: Osteocalcin, osteoprotegerin and osteopontin concentrations were measured at enrollment in 848 participants with T2D from the Sapienza University Mortality and Morbidity Event Rate (SUMMER) Study ( NCT02311244). Logistic regression models and propensity score matching were used to assess possible associations of osteocalcin, osteoprotegerin and osteopontin with history of CVD and with evidence of any grade of DR, adjusting for confounders. RESULTS: Previous CVD was reported in 139 (16.4%) participants, while 144 (17.0%) had DR. After adjusting for possible confounders, osteocalcin but not osteoprotegerin or osteopontin concentrations were associated with a history of CVD (Odds Ratio [OR] and 95% CI for one standard deviation (SD) increase in osteocalcin concentrations (natural log): 1.35 (1.06-1.72), p=0.014). Associations with prevalent DR were seen for osteoprotegerin (OR for one SD increase in osteoprotegerin concentrations (natural log): 1.25 (1.01-1.55), p=0.047) and osteopontin (OR for one SD increase in osteopontin concentrations (natural log): 1.25 (1.02-1.53), p=0.022), but not osteocalcin. CONCLUSIONS: In T2D, higher serum osteocalcin concentrations are associated with macrovascular complications, and higher osteoprotegerin and osteopontin concentrations with microvascular complications, suggesting these osteokines might be involved in pathways directly related to vascular disease. This article is protected by copyright. All rights reserved.

Original publication




Journal article


Diabetes Metab Res Rev

Publication Date



biomarkers, bone-vascular axis, cardiovascular disease, diabetic retinopathy, osteokines, type 2 diabetes