Osteoprotegerin serum levels in children with type 1 diabetes: a potential modulating role in bone status

Abstract

Objective: Children and adolescents with type 1 (insulin-dependent) diabetes mellitus (T1DM) show several impairment of bone metabolism and structure, resulting in a higher risk of decreased bone mass and its related complications later in life. Alterations of the nuclear factor-kB ligand (RANK-L)/osteoprotegerin (OPG) system have been implicated in several metabolic bone diseases characterized by increased osteoclast differentiation and activation and enhanced bone resorption. Design: We aimed to assess OPG levels and to investigate the possible relation between OPG levels, bone status and glycemic control in a group of prepubertal children with T1DM without microvascular complications. Methods: Twenty-six prepubertal T1DM children (median age 9.9 years, range 4.1 -13.1 years) were studied. In all patients, serum OPG, hemoglobin (Hb)A1c, parathyroid hormone (PTH) and 25-dihydroxyvitamin D (25-D) levels were evaluated. Bone quality was determined by measuring the attenuation of ultrasound waves by bone (broadband ultrasound attenuation (BUA)) at the calcaneal site. The data were compared with those of a group of 45 age-, sex-and body-size-matched healthy children. Results: Children with T1DM showed a reduced Z-score BUA in comparison with the control group (Student's t-test, P , 0.0001). Plasma OPG levels were significantly higher in diabetic children than in controls (Student's t-test, P , 0.0001). In T1DM children, Z-score BUA values displayed a significant correlation with OPG (Student's t-test, r ¼ 2 0.62; P ¼ 0.001), and HbA1c (r ¼ 20.59; P ¼ 0.007). OPG levels were significantly correlated with HbA1c (r ¼ 0.56; P ¼ 0.008). In a multiple regression analysis including age, duration of diabetes, physical activity, calcium intake, mean HbA1c and Z-score BUA, only HbA1c significantly predicted serum OPG levels (beta 0.67; P ¼ 0.003). Conclusions: Prepubertal children with T1DM have a significant increase of OPG levels. OPG serum concentrations are correlated to calcaneal BUA and HbA1c values. OPG could be a new marker of reduced bone mass in children with T1DM.European Journal of Endocrinology 153 879-885

Plasma osteoprotegerin levels predict cardiovascular and all-cause mortality and deterioration of kidney function in type 1 diabetic patients with nephropathy

“…This was first shown by Browner et al [12], who reported that although no associations were seen between the bone parameters and plasma osteoprotegerin levels, individuals with diabetes as well as persons with cardiovascular disease had increased values. Since then, these findings have been confirmed in both type 1 [38,39] and type 2 diabetes [13,40]. Moreover, we recently found that plasma osteoprotegerin is increased in subgroups of type 1 diabetic patients with nephropathy and in subgroups with signs of cardiovascular disease [18].…”

An Increased Osteoprotegerin Serum Release Characterizes the Early Onset of Diabetes Mellitus and May Contribute to Endothelial Cell Dysfunction

“…[13][14][15][16][17][18] Therefore, to further analyze whether the serum levels of OPG were affected by hyperglycemia and/or by other aspect of the metabolic disorders associated to diabetes mellitus, such as hypercholesterolemia, the next experiments were performed in the apoE-null mice, 26 which are characterized by elevated levels of total serum cholesterol (mean Ϯ SD, 14.27 Ϯ 2.1 mmol/L) with respect to littermate mice (mean Ϯ SD, 1.81 Ϯ 0.42 mmol/L). In these animals, STZ-induced diabetes mellitus was associated to the development of widespread aortic atherosclerotic lesions, starting from 10 to 12 weeks from diabetes induction onwards ( Figure 3A).…”

“…3,5 It has been shown that OPG is produced by a wide range of tissues, including the cardiovascular system, and that OPG levels are particularly high in aortic and renal arteries. 10 -12 Interestingly, different groups of investigators have reported that serum OPG is significantly increased in both type 1 and type 2 diabetic pa-tients, [13][14][15][16][17][18] as well as in both diabetic and nondiabetic patients affected by coronary artery disease. [17][18][19][20] Moreover, it has been demonstrated that up-regulated serum OPG levels have a negative prognostic value in heart failure after acute myocardial infarction as well as in patients affected by abdominal aortic aneurysm.…”

Bone density and metabolism in subjects with microdeletion of chromosome 22q11 (del22q11)

“…Using an activity questionnaire, physical activity was assessed with a modified activity score composed of the scores for sports/leisure activities (0, !2 or O2 h/week), as previously described (14).…”

“…Calcium dietary intake was assessed with the semiquantitative validated food frequency questionnaire (14). Selection of items was based on the food composition diet, frequency of use and relative importance of food items as a calcium source.…”