The osteoclasts of patients with PYCD are unable to degrade collagen I and other non-collagenous proteins that form the bone matrix, while these cells maintain their demineralizing activity, resulting in abnormal bone metabolism.24, 25 The absence of cathepsin K also seems to stimulate cortical bone formation through the negative control of periostin secreted by osteoblasts and osteocytes, a fact that explains the apparent contradictory effect of the increased bone density in PYCD,26, 27 demonstrated by the presence of osteosclerosis. This evidence concerns the gene POSTN and pycnodysostosis.