Lactoferrin (LF) is a key modulator of inflammatory response. Since bone and immune systems are genetically and functionally linked, we were interested to know if LF could influence bone remodeling. Bovine LF (bLF) inhibited in vitro bone resorbing activity (IC50, 200 mug/ml) in a rabbit mixed bone cell culture, consisting of authentic osteoclasts in an environment of osteoblast and stromal cells. Using human CD14 selected cells committed toward osteoclasts, bLF (10 mug/ml) stimulated cell proliferation. however, led to an inhibition of calcitonin receptor mRNA expression, a main marker of osteoclast phenotype, and decreased the global resorbing activity. No modulation of RANK mRNA expression was observed and mRNA for RANKL and OPG were not detected, that bLF inhibits osteoclastogenesis and reduces bone resorption through a mechanism independent this culture system, suggesting of OPG/RANKL/RANK, In conclusion, bLF appears to modulate bone remodeling. Its mechanism of action remains to be elucidated. (C) 2002 Elsevier Science (USA). All rights reserved.