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J Bone Miner Res, 2017; 32(7): 1537-1545, PMID: 28300329

Insulin Resistance and the IGF-I-Cortical Bone Relationship in Children Ages 9-13 Years.

Year: 2017

Kindler JM, Pollock NK, Laing EM, Oshri A, Jenkins NT, Isales CM, Hamrick MW, Ding KH, Hausman DB, McCabe GP, Martin BR, Hill Gallant KM, Warden SJ, Weaver CM, Peacock M, Lewis RD
Department of Foods and Nutrition, The University of Georgia, Athens, GA, USA.


IGF-I is a pivotal hormone in pediatric musculoskeletal development. Though recent data suggest that the role of IGF-I in total body lean mass and total body bone mass accrual may be compromised in children with insulin resistance, cortical bone geometric outcomes have not been studied in this context. Therefore, we explored the influence of insulin resistance on the relationship between IGF-I and cortical bone in children. A secondary aim was to examine the influence of insulin resistance on the lean mass-dependent relationship between IGF-I and cortical bone. Children were otherwise healthy, early adolescent black and white boys and girls (ages 9-13 years) and were classified as having high (n = 147) or normal (n = 168) insulin resistance based on the homeostasis model assessment of insulin resistance (HOMA-IR). Cortical bone at the tibia diaphysis (66% site) and total body fat-free soft tissue mass (FFST) were measured by pQCT and DXA, respectively. IGF-I, insulin and glucose were measured in fasting sera and HOMA-IR was calculated. Children with high HOMA-IR had greater unadjusted IGF-I (p < 0.001). HOMA-IR was a negative predictor of cortical bone mineral content, cortical bone area (Ct.Ar) and polar strength strain index (pSSI; all p</=0.01) after adjusting for race, sex, age, maturation, fat mass, and FFST. IGF-I was a positive predictor of most musculoskeletal endpoints (all p < 0.05) after adjusting for race, sex, age, and maturation. However, these relationships were moderated by HOMA-IR (pInteraction < 0.05). FFST positively correlated with most cortical bone outcomes (all p < 0.05). Path analyses demonstrated a positive relationship between IGF-I and Ct.Ar via FFST in the total cohort (betaIndirect Effect = 0.321, p < 0.001). However, this relationship was moderated in the children with high (betaIndirect Effect = 0.200, p < 0.001) versus normal (betaIndirect Effect = 0.408, p < 0.001) HOMA-IR. These data implicate insulin resistance as a potential suppressor of IGF-I-dependent cortical bone development, though prospective studies are needed. This article is protected by copyright. All rights reserved.

GID: 4384; Last update: 20.03.2017