Bone quality in pycnodysostosis: micropetrosis, locally distorted osteocyte lacuno-canalicular network, and heterogenous mineralization pattern in an adult female patient with multiple fractures.

Pycnodysostosis is a very rare skeletal dysplasia caused by biallelic loss-of-function mutations in cathepsin K, a proteolytic enzyme highly expressed by osteoclasts. Deficiency of cathepsin K impairs bone resorption and further bone remodeling leading to progressive osteosclerosis and bone fragility. Moreover, cathepsin K is also expressed by mature osteocytes. Whether the density, size, and viability of osteocytes and the osteocyte lacuno-canalicular network (OLCN) are also altered, thereby impacting bone quality in pycnodysostosis, has not been explored. We used light microscopy, quantitative backscattered electron imaging, and confocal laser scanning microscopy to examine bone material obtained from a 57-yr-old female patient during surgical correction after femoral head fracture. The cortex consisted of a compact shell of multilayered collagen fibrils oriented in parallel to the periosteum, reflecting vigorous primary bone apposition, multiple osteons with concentrically ordered lamellae, and scattered patches of woven bone. The trabecular area was very dense with trabecular bone volume, varying locally from 30.3% to 67.4%. The bone matrix was overmineralized (average calcium content: +7.5% versus reference values, with a 5-fold increase of highly mineralized areas >27 weight % calcium). Numerous multinucleated osteoclasts and fringes of demineralized matrix were viewed on bone surfaces. The density (number/mm