Association of Osteoprotegerin with Obesity, Insulin Resistance and Non-Alcoholic Fatty Liver Disease in Children

Abstract

BackgroundOsteoprotegerin (OPG) is a member of the tumor necrosis factor superfamily. Reduced OPG levels are related to obesity, insulin resistance, and non-alcoholic fatty liver disease (NAFLD).ObjectivesThe aim of this study was to evaluate the relationship between OPG levels, obesity, insulin resistance, and NAFLD in pediatric patients.MethodsThis was a prospective, cross-sectional, controlled study that was conducted in the department of pediatrics at Bagcilar training and research hospital in Istanbul, Turkey, between April and August 2015. The study was performed on 107 children with obesity and 37 controls aged 5 - 17 years. In the obese subset, 62 patients had NAFLD. Homeostatic model assessment-insulin resistance (HOMA-IR) was used to calculate insulin resistance. Insulin resistance was defined as a HOMA-IR value greater than 2.5. Plasma OPG levels were measured using enzyme-linked immunosorbent assays. NAFLD was diagnosed by hepatic ultrasound.ResultsThe mean age was 11.25 ± 3.38 years in the patient group and 10.41 ± 3.15 years in the control group. The OPG level in the obese group with the mean of 55.20 ± 24.55 pg/mL (median = 48.81 pg/mL) was significantly lower than that in the control group with the mean of 70.78 ± 33.41 pg/mL (median = 64.57 pg/mL) (P = 0.0001). The optimal cut-off point (sensitivity, specificity) of the OPG level for the diagnosis of obesity was ≤ 46, 19 pg/mL. According to logistic regression analysis, fasting insulin (P = 0.036) and OPG (P = 0.01) levels were most affected by obesity. In the obese patients, who had HOMA-IR < 2.5, the mean level of OPG was 58.91 ± 6.88729 pg/mL (median = 49.55). In the obese patients, who had HOMA-IR ≥ 2.5, the mean level of OPG was 54.19 ± 22.21 pg/mL (median = 48.47). No significant correlations were found between OPG and HOMA-IR (P = 0.791). No statistically significant difference was observed in the mean OPG between patients with hepatosteatosis (mean = 54.55 ± 25.01 pg/mL) (median = 49.46) and those without the disease (56.30 ± 24.02 pg/mL) (mean = 48.34) (P = 0.089).ConclusionsWe confirmed that serum OPG concentrations reduce in obese children. However, no correlation was identified between OPG and insulin resistance. OPG levels are not meaningful in the diagnosis of NAFLD in children with obesity.

The Bone Markers Sclerostin, Osteoprotegerin, and Bone-Specific Alkaline Phosphatase Are Related to Insulin Resistance in Children and Adolescents, Independent of Their Association with Growth and Obesity

“…Two previously published studies, involving a smaller number of adolescents ( n = 98) [13] and adults ( n = 74) [31], respectively, found associations of osteoprotegerin levels with fasting insulin and HOMA-IR, which we did not observe. Our results are consistent with those of Erol et al [14] in 174 children and adolescents; they failed to find an association of osteoprotegerin with HOMA-IR. Though there is a relationship between osteoprotegerin and liver fat in adults [11] which constitutes a risk factor for insulin resistance, the relevance of this bone marker for glucose metabolism, particularly in children and adolescents, remains unclear and is probably minimal.…”

“…In several studies, serum osteoprotegerin has been found to increase with liver fat content [11], and osteoprotegerin levels are higher in adults with diabetes or prediabetes than in those with normal glucose tolerance [12]. In obese adolescents, there was a positive correlation of osteoprotegerin with several parameters of insulin resistance (i.e., fasting serum insulin and HOMA-IR) [13], which was, however, not confirmed by another study including children and adolescents [14]. Another study [15] found that osteoprotegerin levels increased parallel with the physiological increase of insulin resistance during puberty [16].…”

Effects of Sweet Cherry Polyphenols on Enhanced Osteoclastogenesis Associated With Childhood Obesity

“…Previous studies demonstrated that obese subjects showed significantly lower OPG levels respect to the controls (33–35); however no correlation has been reported between OPG and BMI (36, 37). Otherwise, few studies measured higher levels of OPG in obese subjects compared with the controls (38, 39).…”

Body Fat Mass is Better Indicator than Indirect Measurement Methods in Obese Children for Fatty Liver and Metabolic Syndrome

“…This study was demonstrated fatty liver a high frequency seen in obese children and it was more frequency seen in cases with MS. Anthropometric measurements and BIA results was moderately correlated in obese children. Different studies have reported the prevalence of fatty liver in obese children to range from 24%-58% [15,16]. Although liver biopsy is the gold standard in the diagnosis of fatty liver, its invasive application prevents it from being used routinely as a diagnostic method [17].…”