Osteoprotegerin as a possible marker of diabetes-associated osteoarthritis

Abstract

Patients with type 1 diabetes have a higher incidence of osteoarthritis and early manifestation than in the general population. The role of insulin deficiency and hyperglycaemia in the initiation of the destructive process has been proven, but the processes of local and systemic regulation of the balance between anabolic and catabolic processes in the joint and their role in the development of diabetes-associated osteoarthritis remain poorly understood.The aim: to study the role of osteoprotegerin (soluble receptor for tumour necrosis factor - alpha) in the development and progression of diabetes-associated osteoarthritis and its relationship with major metabolic parameters in patients with diabetes mellitus.Materials and methods. 40 patients with type 1 diabetes (17 men and 23 women) were examined, the mean age of the patients was 38.0±2.0 years, the duration of the diabetes was 18.3±1.9 years, the average level of НВА1с was 8.6±0.3 % and 49 patients with type 2 diabetes mellitus (23 men and 26 women), mean age of patients 61.7±1.3 years, duration of diabetes 12.1±1.1 years, mean level HBa1c 7.6±0.1 %. Arthropathy was established in 70.0±7.3 % patients with type 1 diabetes, in 69.4±6.6 % in patients with type 2 diabetes. By sex and type of diabetes, the proportions of patients with and without arthropathy were not statistically different (p> 0.05). The serum content of osteoprotegerin was determined by ELISA using a kit of reagents from Diaclone (France) and enzyme-linked analyser Stat fax 3200 (USA).Results. In patients with arthropathy, a significant increase in osteoprotegerin levels was found. The risk of developing arthropathy in patients with type 1 diabetes with an increased levels of osteoprotegerin is 2.3 times higher than at the normal level (relative risk (RR)=2.33; confidence interval (CI 1.42–3.82; p<0.001), in patients with diabetes 2 type – in 1.55 times (RR=1.55; CI 1.16–1.91). Significant differences in the mean osteoprotegerin level were found for groups absent/present arthropathy. A direct correlation between osteoprotegerin and age was found (p<0.01), diabetes mellitus duration (p <0.05); creatinine level (p<0.05), and an inverse correlation was found with glomerular filtration rate (p<0.05). In the absence of arthropathy, osteoprotegerin and fasting glucose were directly correlated in the type 1 diabetes group (p<0.05). Increased osteoprotegerin levels have been shown to be more common in male patients with longer duration of diabetes. In these patients, no renal lesions were detected, but arthropathy was present as a complication of the underlying disease against the background of an increase in HBA1c.Conclusions. Diabetes-associated osteoarthritis occurs on the background of increased serum osteoprotegerin levels. An increase in the level of osteoprotegerin with an increase in the stage of osteoarthritis was established, so that its level reflects the severity of osteoarthritis. Osteoprotegerin established a direct relationship with the level of creatinine and negatively associated with glomerular filtration rate, i.e. the development and progression of osteoarthritis progression takes place against the background of other vascular complications of diabetes, in particular diabetic nephropathy. An increase in osteoprotegerin is more typical for male patients and depends on the duration of diabetes