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

Joseph M Kindler, Norman K Pollock, Emma M Laing, Assaf Oshri, Nathan T Jenkins, Carlos M Isales, Mark W Hamrick, Ke-Hong Ding, Dorothy B Hausman, George P McCabe, Berdine R Martin, Kathleen M Hill Gallant, Stuart J Warden, Connie M Weaver, Munro Peacock, Richard D Lewis

Research output: Contribution to journalArticlepeer-review

11 Scopus citations

Abstract

IGF-I is a pivotal hormone in pediatric musculoskeletal development. Although 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 to 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 peripheral quantitative computed tomography (pQCT) and dual-energy X-ray absorptiometry (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 (βIndirect Effect  = 0.321, p < 0.001). However, this relationship was moderated in the children with high (βIndirect Effect  = 0.200, p < 0.001) versus normal (βIndirect 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. © 2017 American Society for Bone and Mineral Research.

Original languageEnglish (US)
Pages (from-to)1537-1545
Number of pages9
JournalJournal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research
Volume32
Issue number7
DOIs
StatePublished - Jul 2017
Externally publishedYes

Bibliographical note

© 2017 American Society for Bone and Mineral Research.

Keywords

  • Absorptiometry, Photon
  • Adolescent
  • Blood Glucose/metabolism
  • Bone Density
  • Child
  • Cortical Bone/diagnostic imaging
  • Female
  • Humans
  • Insulin/blood
  • Insulin Resistance
  • Insulin-Like Growth Factor I/metabolism
  • Male
  • Tibia/diagnostic imaging
  • Tomography, X-Ray Computed

PubMed: MeSH publication types

  • Clinical Trial
  • Journal Article
  • Multicenter Study

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