ESPE Yearbook of Paediatric Endocrinology

Introduction: The skeletal research field has produced several important findings during the past year, including advances in the treatment of rare skeletal disorders and an ever deeper understanding of skeletal biology and disorders of mineral metabolism. This year we highlight several advances in the field of skeletal mineralization, ranging from basic mechanisms of tissue mineralization to clinical advances in the understanding of rare disorders characterized by aberrant mineralization.

Translational highlights include several exciting studies including a study demonstrating that retinoic acid inhibition can block hedgehog induced epiphyseal fusion, an article in Endocrinololgy showing that CNP-induced PKA activation promote growth plate chondrogenesis, and study reveling the mechanism by which Fibrillin-1- deficiency promote overgrowth in a mouse model of Marfan syndrome. Novel Advances in skeletal biology feature a Nature article visualizing the conformational changes that turn on and off the the calcium-sensing receptor, a Science article that report that mineralization creates contractile forces in collagen fibrils crucial to the mechanical properties of mineralized bone, and a genetic study explaining the lack of of rare variants to complex trait heritability from SNP-array based genome wide association studies as well as a GWAS show that adult height is predominantly associated with variants in genes that are enriched in the resting zone of the growth plate.

In addition to these areas of progress, the chapter reports several exciting clinical advances including a very large cohort study of fibrous dysplasia reporting fracture rates and fracture risk factors in fibrous dysplasia, a large cohort of patients with ENPP1- or ABCC6-related ectopic calcification and hypophosphatemic rickets, revealing that heterogenous calcification and multiple organ complications occur with both ENPP1 and ABCC6 variants, and thus suggesting overlapping pathology.