Protein undernutrition-induced bone loss is associated with decreased IGF-I levels and estrogen deficiency

Protein undernutrition is a known factor in the pathogenesis of osteoporoti c fracture in the elderly, but the mechanisms of bone loss resulting from t his deficiency are still poorly understood. We investigated the effects of four isocaloric diets with varying levels of protein content (15, 7.5, 5, a nd 2.5 % casein) on areal bone mineral density (BMD), bone ultimate strengt h, histomorphometry, biochemical markers of bone remodeling, plasma IGF-I, and sex hormone status in adult female rats. After 16 weeks on a 2.5% casei n diet, BMD was significantly decreased at skeletal sites containing trabec ular or cortical bone. Plasma IGF-I was decreased by 29-34% and no estrus s ign in vaginal smear was observed. To investigate the roles of estrogen def iciency and protein undernutrition, the same protocol was used in ovariecto mized (OVX) or sham-operated (SHAM) rats, pair-fed isocaloric diets contain ing either 15 or 2.5% casein. Trabecular BMD was decreased by either manipu lation, with effects appearing to be additive. Cortical BMD was decreased o nly in rats on a low-protein diet. This was accompanied by an increased uri nary deoxypyridinoline excretion without any change in osteocalcin levels, suggesting an uncoupling between resorption and formation. Isocaloric prote in undernutrition decreased bone mineral mass and strength. This effect mig ht be related to decreased plasma IGF-I and/or estrogen deficiency with a c onsequent imbalance in bone remodeling.