Calcitropic Hormones and IGF-I Are Influenced by Dietary Protein

Abstract

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.

Low Calcium-Phosphate Intakes Modulate the Low-Protein Diet-Related Effect on Peak Bone Mass Acquisition: A Hormonal and Bone Strength Determinants Study in Female Growing Rats

“…Whereas previous studies have essentially focused on the impact of dietary protein level on bone geometry, mineral content, and midshaft bone strength (4 -6, 36), to the best of our knowledge, no studies have examined the effects of protein deficiency on trabecular bone microarchitecture during growth. Moreover, in agreement with the present results, we previously demonstrated that a low-protein diet impairs trabecular bone microarchitecture in mature rats (10,37).…”

“…However, little is known about their interaction on skeletal growth and the related endocrine regulation. Besides, we know that dietary protein may modulate the secretion and action of calciotropic hormones, (10) and interestingly, the response to calcium supplementation in prepubertal children appears to be influenced by the spontaneous protein intake (23). In this study, we hypothesized that a lowCa/Pi diet may magnify the harmful effect of a low-protein diet on bone growth.…”

Uncarboxylated osteocalcin inhibits high glucose-induced ROS production and stimulates osteoblastic differentiation by preventing the activation of PI3K/Akt in MC3T3-E1 cells

“…Certain studies have also suggested that carboxylated osteocalcin has no effect on mineralization (3)(4)(5). Others have provided evidence that carboxylated osteocalcin may play a role in bone turnover (6,7). Moreover, serum concentrations of osteocalcin have been established as the main marker of bone turnover (8).…”

Modulation of growth hormone receptor-insulin-like growth factor 1 axis by dietary protein in young ruminants

“…However, it was shown that decreased dietary protein intake caused massive changes in mineral homoeostasis and vitamin D metabolism in young goats (4,5) ; this being reflected by reduced levels of blood Ca, 1,25-dihydroxyvitamin D 3 (calcitriol) and insulin-like growth factor 1 (IGF1). Protein restriction was also shown to have an impact on Ca homoeostasis, IGF1 and vitamin D metabolism in monogastric species like humans and rats (6)(7)(8) .…”