AbstractBackgroundOsteoprotegerin (OPG), receptor activator for nuclear factor kappa beta ligand (RANKL) and tumour necrosis factor–related apoptosis‐inducing ligand (TRAIL) are newly discovered members of the tumour necrosis factor‐alpha receptor superfamily. While their role in bone metabolism is well described, their function within the vasculature is poorly understood. OPG inhibits vascular calcification in vitro and high serum levels have been demonstrated in type 2 diabetes, but serum RANKL and TRAIL and their potential correlation with well‐established biomarkers of subclinical vascular inflammation such as high‐sensitivity C‐reactive protein (hsCRP) and interleukin‐6 (IL‐6) have not been described.MethodsSixty‐two patients with well‐controlled type 2 diabetes and an age, gender and body mass index‐matched group of 58 healthy individuals were recruited. Serum OPG, RANKL and TRAIL were measured using commercial enzyme‐linked immunosorbent assays, as were hsCRP and IL‐6.ResultsSerum OPG, IL‐6 and hsCRP levels, but not RANKL or TRAIL, were higher in patients with type 2 diabetes mellitus than in healthy controls, after adjustment for age and gender. After exclusion of diabetes patients with a history of micro‐ or macrovascular disease, OPG remained significantly higher in those with diabetes, but IL‐6 and hsCRP levels were no longer elevated. There was a positive correlation between OPG and IL‐6 in the group as a whole, but no correlation was found between RANKL or TRAIL and either hsCRP or IL‐6.ConclusionOPG, but not RANKL or TRAIL, is significantly increased in type 2 diabetes. Higher OPG (but not IL‐6 or hsCRP) in those without vascular disease suggests these biomarkers reflect separate pathophysiological processes in the vasculature. Copyright © 2010 John Wiley & Sons, Ltd.