High osteoprotegerin is associated with development of foot ulcer in type 1 diabetes

Congratulations to our Danish SALSAmigos for this compelling work.

Background and aim

The bone-related peptide osteoprotegerin has been linked to vascular calcification and peripheral vascular disease. We investigated the association between osteoprotegerin and development of foot complications in persons with type 1 diabetes.

Materials and methods

Prospective observational study of 573 persons with type 1 diabetes, 225 women; age [mean ± SD] 42.3 ± 10.3 years. Plasma osteoprotegerin was measured by ELISA.

Results

Median (IQR) osteoprotegerin was 2.80 (2.35–3.63) μg/L and follow-up time (median (range)) was 12.7 (0.1–15.6) years. Endpoints included: new foot ulceration (n = 153), Charcot foot (n = 14), vascular surgery/amputation (n = 53), loss of foot pulse (n = 57), and peripheral neuropathy (n = 99). In unadjusted analyses, higher osteoprotegerin was associated with development of all endpoints (p ≤ 0.026). Higher osteoprotegerin remained associated with development of foot ulcer, and the combination of vascular surgery/amputation, loss of foot pulse and neuropathy (p ≤ 0.001) in a sex and age adjusted model. After further adjustment (nephropathy status, smoking, HbA_1c, systolic blood pressure, serum cholesterol, high sensitivity C-reactive protein, eGFR, and presence of neuropathy and/or claudication and/or foot ulcer at baseline), higher osteoprotegerin remained associated with development of foot ulcer (HR (95% CI) per doubling: 1.75 (1.04–2.97); p = 0.037).