In conclusion, partial IGF-I deficiency alone is responsible for osteopenia, characterized by reduced bone mass determined by densitometry and histology, associated with a reduced expression of several proteins involved in osteoblastic/osteocyte activity (OPG, SOST, CTR, IGFBP-5 and RUNX2) and with an overexpression of proteins promoting osteoclastic actions, providing at least two mechanisms possibly contributing to the observed reduction on bone mass in Hz mice. Here, CALCR is linked to Osteopenia.