Pentosidine, an Advanced Glycation End Product, Is a Negative Predictor of Cortical Bone Geometric Endpoints in Children

• Published in: The FASEB journal 2017-04, Vol.31 (S1)
• Main Authors: Kindler, Joseph M, Liu, Weixi, Dain, Joel, Laing, Emma, Lewis, Richard M
• Format: Article
• Language: English
• ISSN: 0892-6638; 1530-6860
• DOI: 10.1096/fasebj.31.1_supplement.lb301

Abstract only Advanced glycation end products (AGEs) are suspected to contribute to the increased fracture risk in adults with type‐2 diabetes. In addition to being directly implicated in skeletal fragility, AGEs may adversely influence bone turnover, and consequently, bone mass and geometry. To date, no AGE and bone data have been reported in children. Therefore, the objective of this pilot study was to examine relationships between the AGE pentosidine and cortical bone geometric outcomes in children. Participants were 39 black and white boys and girls (ages 8–13 years) who were in the early stages of sexual maturation. Tibia and radius cortical bone (66% site relative to the distal growth plate) was assessed via peripheral quantitative computed tomography. In fasting sera, insulin (via RIA), glucose (via enzymatic Autokit glucose method), and pentosidine (via ELISA) were measured. The homeostasis model assessment of insulin resistance (HOMA‐IR) was calculated. Linear regression analyses were performed to predict metabolic and cortical bone endpoints from pentosidine. All analyses included race, sex, and sexual maturation rating stage as covariates. For analyses involving cortical bone, muscle cross‐sectional area was included as an additional covariate. Serum insulin (β = 0.346, P = 0.034), but not glucose (β = −0.03, P = 0.866) or HOMA‐IR (β = 0.317, P = 0.056), was a positive predictor of pentosidine. Pentosidine was a negative predictor of tibia cortical bone mineral content (β = −0.266, P = 0.043) and cortical bone area (β = −0.282, P = 0.028), as well as radius total bone area (β = −0.248, P = 0.024), cortical bone area (β = −0.254, P = 0.040), periosteal circumference (β = −0.236, P = 0.033), and polar strength strain index (β = −0.220, P = 0.048). In contrast, pentosidine was positively correlated with radius cortical volumetric bone mineral density (β = 0.347, P = 0.045). We report the first data in children to show inverse relationships between the AGE pentosidine and metabolic and cortical bone geometric endpoints. The role of AGEs, such as pentosidine, warrants further investigation within the context of the increased fracture risk in obese children. Support or Funding Information This research was supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development Grant RO1HD057126, by the Allen Foundation grant 2.008.319, and by the University of Georgia Agricultural Experiment Station, HATCH projects GEO00797 an