Calcitropic hormones and IGF-I are influenced by dietary protein

Endocrinology. 2011 May;152(5):1839-47. doi: 10.1210/en.2010-1079. Epub 2011 Feb 22.


Elderly men and women with protein deficiencies have low levels of circulating IGF-I, and it is likely this contributes to reduced bone formation and increased bone resorption. We hypothesized that calcitropic hormones are involved in this effect and are affected by dietary protein. We therefore investigated the influence of a low-protein diet on the PTH-1,25-dihydroxyvitamin D3 [1,25(OH)₂D₃] axis and IGF-I in rats, using pamidronate to block resorption that normally contributes to mineral homeostasis. We fed 6-month-old Sprague Dawley female rats isocaloric diets containing 2.5% or 15% casein for 2 wk. Pamidronate was then administered sc (0.6 mg/kg/) for 5 d. Blood samples were collected at different time points. Serum 1,25(OH)₂D₃, IGF-I, PTH, calcium, and phosphorus were determined in all rats; vertebral bone strength and histomorphometric analysis were performed in rats subject to the longest low-protein diets. We found 2 wk of low protein increased PTH levels, decreased 1,25(OH)₂D₃, calcium, and IGF-I, suggesting that increased PTH compensates for low-protein-induced decreases in 1,25(OH)₂D₃. Pamidronate augmented the increased PTH after 8 wk of low protein and prevented the 1,25(OH)₂D₃ decrease. IGF-I remained low. Protein malnutrition induced decreases in relative bone volume and trabecular thickness, which was prevented by pamidronate. Maximal load was reduced by protein restriction, but rescued by pamidronate. In summary, the low protein diet resulted in hyperparathyroidism, a reduction in circulating levels of IGF-I, and reduced 1,25(OH)₂D₃ despite hyperparathyroidism. Blocking resorption resulted in further increases in PTH and improved microarchitecture and biomechanical properties, irrespective of vitamin D status or protein intake.

MeSH terms

  • Animals
  • Bone Resorption / blood
  • Bone Resorption / etiology
  • Bone Resorption / prevention & control
  • Bone and Bones / drug effects
  • Bone and Bones / metabolism
  • Bone and Bones / pathology
  • Calcitriol / blood*
  • Calcium / blood
  • Caseins / administration & dosage
  • Caseins / adverse effects
  • Dietary Proteins / administration & dosage*
  • Dietary Proteins / adverse effects
  • Diphosphonates / pharmacology
  • Dose-Response Relationship, Drug
  • Female
  • Hyperparathyroidism / blood
  • Hyperparathyroidism / etiology
  • Hyperparathyroidism / prevention & control
  • Immunoassay / methods
  • Insulin-Like Growth Factor I / analysis*
  • Lumbar Vertebrae / drug effects
  • Lumbar Vertebrae / metabolism
  • Lumbar Vertebrae / pathology
  • Pamidronate
  • Parathyroid Hormone / blood*
  • Rats
  • Rats, Sprague-Dawley
  • Time Factors
  • Vitamin D / analogs & derivatives


  • Caseins
  • Dietary Proteins
  • Diphosphonates
  • Parathyroid Hormone
  • dihydroxy-vitamin D3
  • Vitamin D
  • Insulin-Like Growth Factor I
  • Calcitriol
  • Pamidronate
  • Calcium