Further studies suggest that Dkk-1 is a key inhibitor of systemic bone formation, like increased bone mass and osteoblast activity in Dkk-1 deficient mice [27,53] and osteopenia in mice over-expressing Dkk-1 [30]; in naïve normal growing female mice, human monoclonal anti-Dkk-1 antibodies are able to significantly improve both trabecular and cortical bone mineral densities [28]. This evidence concerns the gene DKK1 and Osteopenia.