Sprouty proteins are modulators of the MAPK/ERK pathway. Amongst these, Sprouty2 (SPRY2) has been investigated as a possible factor that takes part in the initial phases of osteogenesis. However, the context has not yet been investigated and the underlying mechanisms taking place remain unknown. Therefore, in this study, the impact of deficiency was examined in the developing tibias of deficient () mouse. The investigation was performed when the osteogenic zone became clearly visible and when all three basic bone cells types were present. The main markers of osteoblasts, osteocytes and osteoclasts were evaluated by immunohistochemistry and RT-PCR. RT-PCR showed that the expression of was 3.5 times higher in than in the wild-type bone, which pointed to a still unknown mechanism of action of SPRY2 on the differentiation of osteocytes. The up-regulation of was independent of expression and could not be related to its positive regulator, , since none of these factors showed an increased expression in the bone of mice. Regarding the RANK/RANKL/OPG pathway, the showed an increased expression of , but no significant change in the expression of and . Thanks to these results, the impact of deletion is shown for the first time in the developing bone as a complex organ including, particularly, an effect on osteoblasts () and osteocytes (). This might explain the previously reported decrease in bone formation in postnatal mice.