Bovine lactoferrin is efficient for improving bone characteristics: a study based on a new preclinical model of marked bone fragility

Abstract

Osteoporosis is associated with postmenopausal estrogen deficiency in women. Reduction of protein intake further decreases bone quality in these individuals. In this study, a new experimental model using ovariectomized mice with moderate alimentary protein restriction was used to evaluate the efficiency of lactoferrin, a protein present in milk, on bone mineral density (BMD), 3D-microarchitecture, and different physiological and biochemical parameters. Twelve-week-old female C3H mice were ovariectomized (OVX) or sham-operated (SHAM), and a group of mice were then fed for 3 months with a normal protein diet (NP: 20% of total energy as soy protein), while another group of mice were fed with a low protein diet (LP: 6% of total energy as soy protein) in which 10 g of soy protein was replaced by 10 g of bovine lactoferrin (bLF). Casein was used as a control for bLF. BMD was measured by dual energy X-ray absorptiometry, and the femurs of mice were imaged by microtomography. The effects of the OVX procedure, which were found to depend on the protein level in the diet, were notably significant reduction of BMD and bone quality in both conditions of protein supply. Indeed, a 35% and 70% reduction of the bone volume/tissue ratio were found for the NP OVX and LP OVX mice respectively. The greater bone loss observed in LP OVX mice did not correlate with a change in the ratio of bone formation or resorption, but with a decrease in circulating IGF-1 level. Supplementation of both diets with bLF significantly improved bone quality in OVX mice. In conclusion, the model of ovariectomized mice with moderate protein restriction appears suitable to mimic the marked alteration of bone quality in postmenopausal women with insufficient protein supply. In such a preclinical model, supplementation with bLF is efficient for improving bone characteristics.