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

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, B-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/IG FBP-3 (1:4, 2.5 mg IGF-I/kg BW) or with vehicle for 10 days. After double-l abeling, proximal metaphysis and mid-diaphysis of the tibia were analyzed h istomorphometrically. Plasma ostcocalcin, IGF-I, and urinary deoxypyridinol ine were quantified. After 14 days of protein restriction, significant drop s in plasma osteocalcin (13%) and IGF-I (37%), in periosteal formation (83% ) and mineral apposition (49%) rates are observed, indicating a decreased o steoblast recruitment and activity. In cancellous bone, a significant decre ase 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 rat s, rhIGF-I/IGFBP-3 fails to increase cancellous or periosteal bone formatio n 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.