Regular ArticleOsteoprotegerin is higher in peripheral arterial disease regardless of glycaemic status☆
Section snippets
Materials and Methods
Patients with documented type 2 diabetes and peripheral arterial disease were recruited from the diabetes and vascular surgery clinics in Beaumont Hospital, Dublin, Ireland. The healthy control subjects were recruited from Dublin City University, Ireland. The control group had no symptoms of intermittent claudication, normal peripheral foot pulses, no evidence of PAD on ankle brachial index (ABI) measurement, had normal glucose tolerance, as measured by a 75 gm oral glucose tolerance test
Results
There were 26 patients with PAD and DM (Group 1), 35 with DM and no PAD (Group 2), 22 with PAD and no DM (Group 3), and 21 healthy controls with neither DM nor PAD (Group 4). Demographic characteristics of the 4 groups are displayed in Table 1. All groups were matched for BMI and BMD. Healthy controls (Group 4) were younger, had lower blood pressure, lower use of statins, aspirin and medications affecting the renin-angiotensin system, lower fasting plasma glucose, higher fasting cholesterol and
Discussion
While great progress has been made in the identification of the action of the OPG/RANKL/TRAIL pathway in bone, its role in the vasculature is incompletely understood. In-vitro work suggests OPG acts as an anti-calcifying agent in vessels [5], [6] and numerous studies have consistently shown elevated levels in patients with coronary artery disease [8], [9], [10]. There has been conflicting data reported on serum OPG in individuals with PAD - a disease of marked vascular calcification.
Our finding
Conclusions
We found serum OPG, TRAIL, hsCRP and IL-6 (but not RANKL) to be significantly elevated in patients with PAD. Only OPG remained elevated in those with PAD regardless of the presence of type 2 diabetes. Additionally, only OPG correlated (negatively) with the severity of PAD as defined by ABI. These findings suggest OPG may be a more robust marker of peripheral arterial disease activity than more established biomarkers such as IL-6 and hsCRP, but further work is needed to further investigate these
Conflict of interest
There is no conflict of interest.
References (36)
- et al.
Osteoprotegerin is a receptor for the cytotoxic ligand TRAIL
J Biol Chem
(Jun 5 1998) - et al.
The relationship between plasma osteoprotegerin levels and coronary artery calcification in uncomplicated type 2 diabetic subjects
J Am Coll Cardiol
(May 2 2006) - et al.
Prognostic value of osteoprotegerin in heart failure after acute myocardial infarction
J Am Coll Cardiol
(Nov 16 2004) - et al.
Circulating osteoprotegerin levels and long-term prognosis in patients with acute coronary syndromes
J Am Coll Cardiol
(Feb 12 2008) - et al.
Osteoprotegerin plasma concentrations correlate with severity of peripheral artery disease
Atherosclerosis
(Sep 2005) - et al.
An increased osteoprotegerin serum release characterizes the early onset of diabetes mellitus and may contribute to endothelial cell dysfunction
Am J Pathol
(Dec 2006) - et al.
Relationship of elevated osteoprotegerin with insulin resistance, CRP, and TNF-alpha levels in men with type 2 diabetes
Cytokine
(Oct 2008) - et al.
Inter-Society Consensus for the Management of Peripheral Arterial Disease (TASC II)
J Vasc Surg
(Jan 2007) - et al.
The role of biomarkers and genetics in peripheral arterial disease
J Am Coll Cardiol
(Sep 29 2009) - et al.
Peripheral arterial disease detection, awareness, and treatment in primary care
JAMA
(Sep 19 2001)
Vascular calcifications as a marker of increased cardiovascular risk: a meta-analysis
Vasc Health Risk Manag
Osteoprotegerin-deficient mice develop early onset osteoporosis and arterial calcification
Genes Dev
Osteoprotegerin reverses osteoporosis by inhibiting endosteal osteoclasts and prevents vascular calcification by blocking a process resembling osteoclastogenesis
J Exp Med
Osteoprotegerin inhibits artery calcification induced by warfarin and by vitamin D
Arterioscler Thromb Vasc Biol
Serum osteoprotegerin levels are associated with the presence and severity of coronary artery disease
Circulation
Increased osteoprotegerin serum levels in men with coronary artery disease
J Clin Endocrinol Metab
Relationship of serum osteoprotegerin levels with coronary artery disease severity, left ventricular hypertrophy and C-reactive protein
Clin Sci (Lond)
Associations of serum osteoprotegerin levels with diabetes, stroke, bone density, fractures, and mortality in elderly women
J Clin Endocrinol Metab
Cited by (23)
High osteoprotegerin is associated with development of foot ulcer in type 1 diabetes
2016, Journal of Diabetes and its ComplicationsCitation Excerpt :In a large prospective study with 10-year follow-up including 1939 type 1 diabetic participants, an association between OPG and lower limb vascularization or amputation was found with a HR per 0.2 mg/L increase in OPG of 1.46 (1.33–1.88) after adjustment for other factors associated with serum OPG concentrations (Gordin et al., 2013). Moreover, recent cross-sectional studies have demonstrated that higher OPG correlates with peripheral vascular disease in participants with type 2 diabetes (Esteghamati et al., 2015; O'Sullivan et al., 2010; Poulsen et al., 2011; Singh et al., 2012). In our study, OPG was associated with loss of foot pulse and the combined endpoint of vascular surgery and amputation in sex and age adjusted models; however, the association lost significance after comprehensive adjustment.
Circulating osteoprotegerin and asymptomatic carotid atherosclerosis in postmenopausal non diabetic women
2014, Advances in Medical SciencesCitation Excerpt :At the level of the vascular wall, vascular smooth muscle cells and endothelial cells are the main sources of OPG and its expression is related to inflammatory mediators [1,3,5]. Although animal studies indicated a protective role for OPG in arteries [6], human studies have shown a positive association between serum OPG and different cardiovascular diseases, including coronary artery disease, acute myocardial infarction, peripheral vascular disease, left ventricular dysfunction or stroke [7–12]. Postmenopausal women seem to have an increased cardiovascular risk that is linked with the secession of estrogen production considered to have a cardioprotective effect [13].
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Data from this manuscript was presented at meetings in 2009 of the American Diabetes Association in New Orleans, USA and Diabetes UK in Glasgow, Scotland.