Pentosidine Is Associated With Cortical Bone Geometry and Insulin Resistance in Otherwise Healthy Children

Abstract

Pentosidine is an advanced glycation end product (AGE) associated with fracture in adults with diabetes. AGE accumulation in bone collagen contributes to bone fragility but might also adversely influence bone turnover and, consequently, bone geometry. The relationships between AGEs and bone health have yet to be studied in children. Thus, the objective of this study was to assess relationships between pentosidine and cortical bone volumetric density, geometry, and estimated strength in children. Participants were otherwise healthy black and white boys and girls, ages 9 to 13 years, who were at sexual maturation stage 2 or 3 (N = 160). Tibia and radius cortical bone and muscle area (66% site) were assessed via pQCT. In fasting sera, insulin, glucose, and pentosidine were measured. The Quantitative Insulin Sensitivity Check Index (QUICKI), a measure of insulin sensitivity, was calculated. While controlling for race, sex, maturation, and height, pentosidine negatively correlated with QUICKI (P < 0.05). In unadjusted analyses, pentosidine was associated with lower radius and tibia cortical volumetric bone mineral density, bone mineral content (Ct.BMC), area (Ct.Ar), and thickness (Ct.Th); a larger radius endosteal circumference (Endo.Circ); and lower tibia polar strength strain index (all P < 0.05). While controlling for race, sex, maturation, height, and muscle area, pentosidine was negatively associated with tibia Ct.BMC, Ct.Ar, and Ct.Th but positively associated with Endo.Circ (all P < 0.05). Linear regression revealed a significant interaction between pentosidine and QUICKI in relation to tibia Ct.Th (p_interaction = 0.049), indicating that the negative relationship between pentosidine and Ct.Th was stronger in those with lower QUICKI (ie, greater insulin resistance). This is the first study to report evidence of a potentially adverse influence of AGEs on bone strength in otherwise healthy children. This relationship was strongest in children with the greatest insulin resistance, supporting further work in youth with chronic metabolic health conditions. © 2019 American Society for Bone and Mineral Research.

Keywords: ADVANCED GLYCATION END PRODUCT; BONE GEOMETRY IN CHILDREN; INSULIN RESISTANCE; PENTOSIDINE.