Metabolic phenotype in the mouse model of osteogenesis imperfecta

J Endocrinol. 2017 Sep;234(3):279-289. doi: 10.1530/JOE-17-0335. Epub 2017 Jul 17.


Osteogenesis imperfecta (OI) is the most common heritable bone fragility disorder, usually caused by dominant mutations in genes coding for collagen type I alpha chains, COL1A1 or COL1A2 Osteocalcin (OCN) is now recognized as a bone-derived regulator of insulin secretion and sensitivity and glucose homeostasis. Since OI is associated with increased rates of bone formation and resorption, we hypothesized that the levels of undercarboxylated OCN are increased in OI. The objective of this study was to determine changes in OCN and to elucidate the metabolic phenotype in the Col1a1Jrt/+ mouse, a model of dominant OI caused by a Col1a1 mutation. Circulating levels of undercarboxylated OCN were higher in 4-week-old OI mice and normal by 8 weeks of age. Young OI animals exhibited a sex-dependent metabolic phenotype, including increased insulin levels in males, improved glucose tolerance in females, lower levels of random glucose and low adiposity in both sexes. The rates of O2 consumption and CO2 production, as well as energy expenditure assessed using indirect calorimetry were significantly increased in OI animals of both sexes, whereas respiratory exchange ratio was significantly higher in OI males only. Although OI mice have significant physical impairment that may contribute to metabolic differences, we specifically accounted for movement and compared OI and WT animals during the periods of similar activity levels. Taken together, our data strongly suggest that OI animals have alterations in whole body energy metabolism that are consistent with the action of undercarboxylated osteocalcin.

Keywords: glucose homeostasis; indirect calorimetry; metabolism; osteogenesis imperfecta; undercarboxylated osteocalcin.

MeSH terms

  • Animals
  • Collagen Type I / genetics
  • Collagen Type I / metabolism
  • Disease Models, Animal
  • Female
  • Humans
  • Male
  • Mice
  • Osteocalcin / genetics
  • Osteocalcin / metabolism
  • Osteogenesis Imperfecta / genetics
  • Osteogenesis Imperfecta / metabolism*
  • Phenotype


  • Collagen Type I
  • Osteocalcin