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 language | English (US) |
|---|---|
| Pages (from-to) | 1537-1545 |
| Number of pages | 9 |
| Journal | Journal of Bone and Mineral Research |
| Volume | 32 |
| Issue number | 7 |
| DOIs | |
| State | Published - Jul 2017 |
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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 journal › Article
}
TY - JOUR
T1 - Insulin Resistance and the IGF-I-Cortical Bone Relationship in Children Ages 9 to 13 Years
AU - Kindler, Joseph M.
AU - Pollock, Norman K.
AU - Laing, Emma M.
AU - Oshri, Assaf
AU - Jenkins, Nathan T.
AU - Isales, Carlos M.
AU - Hamrick, Mark W.
AU - Ding, Ke Hong
AU - Hausman, Dorothy B.
AU - McCabe, George P.
AU - Martin, Berdine R.
AU - Hill Gallant, Kathleen M.
AU - Warden, Stuart J.
AU - Weaver, Connie M.
AU - Peacock, Munro
AU - Lewis, Richard D.
PY - 2017/7
Y1 - 2017/7
N2 - 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.
AB - 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.
KW - BONE QCT/µCT
KW - GH/IGF-I
KW - SKELETAL MUSCLE
KW - pQCT
UR - http://www.scopus.com/inward/record.url?scp=85021322537&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85021322537&partnerID=8YFLogxK
U2 - 10.1002/jbmr.3132
DO - 10.1002/jbmr.3132
M3 - Article
C2 - 28300329
AN - SCOPUS:85021322537
VL - 32
SP - 1537
EP - 1545
JO - Journal of Bone and Mineral Research
JF - Journal of Bone and Mineral Research
SN - 0884-0431
IS - 7
ER -