Dietary Protein Restriction Lowers Plasma Insulin-Like Growth Factor I (IGF-I), Impairs Cortical Bone Formation, and Induces Osteoblastic Resistance to IGF-I in Adult Female Rats

• Published in: Endocrinology (Philadelphia) 2000-09, Vol.141 (9), p.3149-3155
• Main Authors: Bourrin, S., Ammann, P., Bonjour, J. P., Rizzoli, R.
• Format: Article
• Language: English
• Subjects: Animals; Apposition; Biomarkers; Body Weight - drug effects; Bone and Bones - cytology; Bone Development - physiology; Bone growth; Bone mineral density; Bone resorption; Bone Resorption - pathology; Cancellous bone; Casein; Cortical bone; Deoxypyridinoline; Diaphysis; Diet; Dietary Proteins - administration & dosage; Dietary restrictions; Drug Resistance; Female; Females; Growth factors; Insulin; Insulin-Like Growth Factor Binding Protein 3 - pharmacology; Insulin-like growth factor I; Insulin-Like Growth Factor I - metabolism; Insulin-Like Growth Factor I - pharmacology; Insulin-like growth factor-binding protein 3; Insulin-like growth factors; Metaphysis; Organ Size - drug effects; Osteoblasts; Osteoblasts - drug effects; Osteocalcin; Osteogenesis; Plasma; Protein deficiency; Proteins; Rats; Rats, Sprague-Dawley; Recombinant Proteins - pharmacology; Tibia
• ISSN: 0013-7227; 1945-7170
• DOI: 10.1210/endo.141.9.7633

Abstract Dietary protein deficiency, common in elderly, is associated with decreased areal bone mineral density and plasma insulin-like growth factor I (IGF-I). To investigate the early adaptation of bone cells to protein restriction, 6-month-old female rats were pair-fed with isocaloric 15% (control) or 2.5% casein diets for 14 days. Animals were then treated daily with rhIGF-I/IGFBP-3 (1:4, 2.5 mg IGF-I/kg BW) or with vehicle for 10 days. After double-labeling, proximal metaphysis and mid-diaphysis of the tibia were analyzed histomorphometrically. Plasma osteocalcin, IGF-I, and urinary deoxypyridinoline were quantified. After 14 days of protein restriction, significant drops in plasma osteocalcin (13%) and IGF-I (37%), in periosteal formation (83%) and mineral apposition (49%) rates are observed, indicating a decreased osteoblast recruitment and activity. In cancellous bone, a significant decrease in active eroded surfaces (27%) and osteoclast number (24%) indicates a transient depression of resorption. In rats fed the 15% casein diet, rhIGF-I/IGFBP-3 increases cancellous (42%) and periosteal (600%) formation rates, indicating an increased osteoblast recruitment. In protein-restricted rats, rhIGF-I/IGFBP-3 fails to increase cancellous or periosteal bone formation and plasma osteocalcin is significantly lower than in 15% casein+rhIGF-I/IGFBP-3 rats. Protein restriction induces osteoblast resistance to rhIGF-I/IGFBP-3 in both bone envelopes. Low plasma IGF-I and osteoblast resistance to IGF-I, may contribute to the impaired periosteal formation.