Osteoprotegerin is higher in peripheral arterial disease regardless of glycaemic status

Introduction: Peripheral arterial disease (PAD) and type 2 diabetes mellitus (DM) are both associated with excessive vascular calcification and elevated levels of inflammatory markers IL-6 and hsCRP. The recently identified Osteoprotegerin(OPG)/RANKL/TRAIL pathway has been implicated in vascular calcification, but data on levels in PAD and effect of co-existent DM are lacking. Materials and Methods: 4 groups of patients were recruited - 26 with PAD and DM, 35 with DM alone, 22 with PAD alone, and 21 healthy individuals. Serum OPG, RANKL, TRAIL, hsCRP and IL-6 were measured using commercial ELISA assays. Presence and severity of PAD was defined using ankle brachial index (ABI). Results: Serum OPG (7.4 +/- 0.3 vs. 5.8 +/- 0.2 pmol/l, p < 0.0001), TRAIL (95.5 +/- 5.2 ng/ml vs. 76.2 +/- 4.4 ng/ml, p = 0.006), hsCRP (2.6 +/- 0.3 vs. 1.8 +/- 0.3 mg/l, p = 0.048), and IL-6 (4.1 +/- 0.4 vs. 2.9 +/- 0.4 pg/ml, p = 0.06) were higher in patients with PAD. There was no difference in RANKL. Only OPG was significantly higher in PAD and DM (7.2 +/- 0.3 pmol/l) and PAD alone (7.7 +/- 0.4 pmol/l) compared to DM only (5.8 +/- 0.3 pmol/l) and healthy controls (5.6 +/- 0.4 pmol/l), p < 0.01, but OPG was no higher in those with DM plus PAD versus those with PAD alone (p < 0.3). Only OPG was associated with PAD severity, correlating negatively with ABI (r = -0.26, p = 0.03), independent of age, gender, glycaemic status, hsCRP and IL-6. Conclusions: PAD is associated with higher serum OPG, regardless of the co-existence of DM. This finding, in addition to its correlation with severity of PAD, suggests that OPG may be a novel marker for the presence and severity of PAD, possibly by reflecting the degree of underlying vascular calcification. (C) 2010 Elsevier Ltd. All rights reserved.