ESPE Yearbook of Paediatric Endocrinology

Preface: The skeletal research field continues to develop rapidly and produced several seminal findings during the last year, including advances in the treatment of rare skeletal disorders, and an ever deeper understanding of skeletal stem cell biology and hormone receptor signalling mechanisms. The targeting of the C-type natriuretic peptide (CNP) pathway as a way to antagonize the overactivity of the FGFR3 pathway in achondroplasia has been a subject of tremendous interest and excitement during the last couple of years and we here highlight the first phase 2 study with growth data up to 42 months of treatment with a CNP analogue (vosoritide) in children with achondroplasia. We also highlight skeletal outcomes after discontinuation of bisphosphonates in patients with osteogenesis imperfecta, as well as a clinical follow up study detailing the skeletal changes following hematopoietic stem cell transplantation in patients with osteopetrosis.

Additional highlights include a study from the Journal of Clinical Investigation unravelling the downstream mediators PTH/PTHrP receptor signalling in skeletal development and metabolism, a Nature article revealing that lipid availability is an important determinant of skeletal stem cell differentiation in fracture healing. In addition, the powerful technology of cell-tracing continues to reveal more details on the origin and fate of different skeletal cell populations. A report in the Journal of Bone and Mineral Research shows that Pthrp positive growth plate chondrocytes adjacent to the perichondrium act as mesenchymal stem cells providing metaphyseal osteoblast/osteocytes as well as reticular stromal cells to the bone marrow, confirming the stemness and versatility of growth plate chondrocyte.

In addition to these areas of progress, the chapter reports several exciting translational findings including a specific phosphate binding site in the calcium-sensing receptor that stabilizes the inactive conformation, thus increasing PTH expression during hyperphosphatemia, as well as promising results in a mouse model of fibrous dysplasia indicating that RANKL-inhibition can not only prevent the development of new fibrous dysplasia lesions, but also decrease the size and increase mineralization of existing lesions.