Insulin Resistance Is Associated With Smaller Cortical Bone Size in Nondiabetic Men at the Age of Peak Bone Mass

J Clin Endocrinol Metab. 2017 Jun 1;102(6):1807-1815. doi: 10.1210/jc.2016-3609.

Abstract

Context: In type 2 diabetes mellitus, fracture risk is increased despite preserved areal bone mineral density. Although this apparent paradox may in part be explained by insulin resistance affecting bone structure and/or material properties, few studies have investigated the association between insulin resistance and bone geometry.

Objective: We aimed to explore this association in a cohort of nondiabetic men at the age of peak bone mass.

Design, setting, and participants: Nine hundred ninety-six nondiabetic men aged 25 to 45 years were recruited in a cross-sectional, population-based sibling pair study at a university research center.

Main outcome measures: Insulin resistance was evaluated using the homeostasis model assessment of insulin resistance (HOMA-IR), with insulin and glucose measured from fasting serum samples. Bone geometry was assessed using peripheral quantitative computed tomography at the distal radius and the radial and tibial shafts.

Results: In age-, height-, and weight-adjusted analyses, HOMA-IR was inversely associated with trabecular area at the distal radius and with cortical area, periosteal and endosteal circumference, and polar strength strain index at the radial and tibial shafts (β ≤ -0.13, P < 0.001). These associations remained essentially unchanged after additional adjustment for dual-energy X-ray absorptiometry-derived body composition, bone turnover markers, muscle size or function measurements, or adiponectin, leptin, insulin-like growth factor 1, or sex steroid levels.

Conclusion: In this cohort of nondiabetic men at the age of peak bone mass, insulin resistance is inversely associated with trabecular and cortical bone size. These associations persist after adjustment for body composition, muscle size or function, or sex steroid levels, suggesting an independent effect of insulin resistance on bone geometry.

MeSH terms

  • Absorptiometry, Photon
  • Adiponectin / metabolism
  • Adult
  • Blood Glucose / metabolism
  • Body Composition
  • Bone Density
  • Chromatography, Liquid
  • Collagen Type I / metabolism
  • Cortical Bone / diagnostic imaging*
  • Cortical Bone / pathology
  • Estradiol / metabolism
  • Humans
  • Insulin / metabolism
  • Insulin Resistance*
  • Insulin-Like Growth Factor I / metabolism
  • Leptin / metabolism
  • Male
  • Middle Aged
  • Muscle Strength
  • Muscle, Skeletal / diagnostic imaging
  • Muscle, Skeletal / pathology
  • Organ Size
  • Osteocalcin / metabolism
  • Parathyroid Hormone / metabolism
  • Peptide Fragments / metabolism
  • Peptides / metabolism
  • Procollagen / metabolism
  • Radius / diagnostic imaging*
  • Radius / pathology
  • Serum Albumin / metabolism
  • Sex Hormone-Binding Globulin / metabolism
  • Tandem Mass Spectrometry
  • Testosterone / metabolism
  • Tibia / diagnostic imaging*
  • Tibia / pathology
  • Tomography, X-Ray Computed
  • Vitamin D / analogs & derivatives
  • Vitamin D / metabolism

Substances

  • ADIPOQ protein, human
  • Adiponectin
  • Blood Glucose
  • Collagen Type I
  • Insulin
  • Leptin
  • Parathyroid Hormone
  • Peptide Fragments
  • Peptides
  • Procollagen
  • Serum Albumin
  • Sex Hormone-Binding Globulin
  • collagen type I trimeric cross-linked peptide
  • procollagen type I carboxy terminal peptide
  • Osteocalcin
  • Vitamin D
  • Testosterone
  • Estradiol
  • Insulin-Like Growth Factor I
  • 25-hydroxyvitamin D