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 (pinteraction = 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.

Dysbiosis of Oral Microbiota and Metabolite Profiles Associated with Type 2 Diabetes Mellitus

“…The increase in cadaverine content leads to damage to the dental epithelial barrier, which aggravates periodontitis ( 36 ). As an advanced glycation end product (AGE), pentosidine may promote oxidative stress and endothelial dysfunction ( 37 ) and inhibit the formation of bone nodules, resulting in bone fragility ( 38 ). Campylobacter concisus abundance increased significantly among the supragingival plaque microorganisms of T2DM patients and showed a positive correlation with the levels of the metabolite n , n -dimethylarginine.…”

Effect of Antidiabetic Drugs on Bone Health in Patients with Normal Renal Function and in Chronic Kidney Disease (CKD): Insight into Clinical Challenges in the Treatment of Type 2 Diabetes

“…Other factors contributing to impaired bone strength in T2DM are the accumulation of advanced glycation end products (AGEs), particularly pentosidine, insulin resistance, inflammatory cytokines, oxidative stress, and microvascular damage [23]. Emerging evidence suggests that serum AGEs concentration is inversely associated with indexes of cortical bone quality; additionally, AGEs content in the cortical, but not in the trabecular bone, is increased in T2DM [24,25]. A higher concentration of AGEs was observed in the collagen matrix of trabecular specimens collected during hip arthroplasty in T2DM subjects and associated with impaired bone strength [26].…”

Glycemic Control and Bone in Diabetes

“…Accumulation of AGEs contributes to diabetes-related complications, including bone fragility [ 71 ]. Pentosidine and carboxy-methyl-lysine (CML) have been associated with bone structural deficits and increased risk for fracture and bone deficits in healthy and diabetic populations [ 80 , 83 – 85 ]. Most recently, Dhaliwal et al utilized data from the Health, Aging, and Body Composition (Health ABC) cohort of older adults, approximately 74 years of age, to assess associations between CML and incident and prevalent vertebral fractures [ 86 ••].…”