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 journalArticle

6 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)1537-1545
Number of pages9
JournalJournal of Bone and Mineral Research
Volume32
Issue number7
DOIs
StatePublished - Jul 2017

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Insulin-Like Growth Factor I
Insulin Resistance
Homeostasis
Fats
Sexual Maturation
Musculoskeletal Development
Cortical Bone
Cohort Effect
Diaphyses
Bone Development
Photon Absorptiometry
Tibia
Bone Density
Adipose Tissue
Fasting
Tomography
Hormones
Prospective Studies
Insulin
Pediatrics

Keywords

  • BONE QCT/µCT
  • GH/IGF-I
  • SKELETAL MUSCLE
  • pQCT

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Orthopedics and Sports Medicine

Cite this

Insulin Resistance and the IGF-I-Cortical Bone Relationship in Children Ages 9 to 13 Years. / Kindler, Joseph M.; Pollock, Norman K.; Laing, Emma M.; Oshri, Assaf; Jenkins, Nathan T.; Isales, Carlos M.; Hamrick, Mark W.; Ding, Ke Hong; Hausman, Dorothy B.; McCabe, George P.; Martin, Berdine R.; Hill Gallant, Kathleen M.; Warden, Stuart J.; Weaver, Connie M.; Peacock, Munro; Lewis, Richard D.

In: Journal of Bone and Mineral Research, Vol. 32, No. 7, 07.2017, p. 1537-1545.

Research output: Contribution to journalArticle

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 2017, 'Insulin Resistance and the IGF-I-Cortical Bone Relationship in Children Ages 9 to 13 Years', Journal of Bone and Mineral Research, vol. 32, no. 7, pp. 1537-1545. https://doi.org/10.1002/jbmr.3132
Kindler, Joseph M. ; Pollock, Norman K. ; Laing, Emma M. ; Oshri, Assaf ; Jenkins, Nathan T. ; Isales, Carlos M. ; Hamrick, Mark W. ; Ding, Ke Hong ; Hausman, Dorothy B. ; McCabe, George P. ; Martin, Berdine R. ; Hill Gallant, Kathleen M. ; Warden, Stuart J. ; Weaver, Connie M. ; Peacock, Munro ; Lewis, Richard D. / Insulin Resistance and the IGF-I-Cortical Bone Relationship in Children Ages 9 to 13 Years. In: Journal of Bone and Mineral Research. 2017 ; Vol. 32, No. 7. pp. 1537-1545.
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