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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 Rats¹

Division of Bone Diseases, World Health Organization Collaborating Center for Osteoporosis and Bone Diseases, Department of Internal Medicine, University Hospital, Geneva CH-1211, Switzerland

Address all correspondence and requests for reprints to: Sandrine Bourrin, Ph.D., Division of Bone Diseases, Department of Internal Medicine, University Hospital of Geneva, Rue Micheli-du-Crest, 24, CH- 1211 Geneva 14, Switzerland.

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.

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