Mechanisms underlying growth impairment and bone deformities in X-linked hypophosphatemia are not fully understood. We here describe marked alterations in the structure, dynamics and maturation of growth plate in growth-retarded young Hyp mice, in comparison with wild type mice. Hyp mice exhibited reduced proliferation and apoptosis rates of chondrocytes as well as severe disturbance in the process of chondrocyte hypertrophy disclosed by abnormal expression of proteins likely involved in cell enlargement, irregular chondro-osseous junction and disordered bone trabecular pattern and vascular invasion in the primary spongiosa. (Hyp mice had elevated circulating FGF23 levels and over activation of ERK in the growth plate.) All these findings provide a basis to explain growth impairment and metaphyseal deformities in XLH. Hyp mice were compared with wild type mice serum parameters, nutritional status and growth impairment by evaluation of growth cartilage and bone structures. Hyp mice presented hyphosphatemia with high FGF23 levels. Weight gain and longitudinal growth resulted reduced in them with numerous skeletal abnormalities at cortical bone. It was also observed aberrant trabecular organization at primary spongiosa and atypical growth plate organization with abnormal proliferation and hypertrophy of chondrocytes and diminished apoptosis and vascular invasion processes. The present results show for the first time the abnormalities present in the growth plate of young Hyp mice and suggest that both cartilage and bone alterations may be involved in the growth impairment and the long bone deformities of XLH.