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 mi...

PrefaceThe skeletal research field continues to develop rapidly and has produced several seminal findings in the last year including advances in the treatment of rare skeletal disorders, and an even deeper understanding into the molecular mechanisms that control skeletal development, endochondral bone formation, mineralization of skeletal tissues and skeletal biology. The targeting of the C-type natriuretic peptide (CNP) pathway and options to directly a...

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 a...

Preface: It has been an exciting year for life science in the skeletal research field with several seminal findings ranging from basic science and genetics to novel successful treatments. The powerful technology of cell-tracing is developing and is bringing new understanding to the identity and behaviour of skeletal stem cells. Two reports in Nature have identified the perichondrial stem cell pool that contribute bone cells to the periosteum as well as the behaviour o...

Abstract: Endocrinology. 2018 Mar 1;159(3):1469–1478.In brief: In this article, a combination of microdissection, miroRNA profiling and transfection studies identify 3 microRNAs that are highly expressed in the proliferative zone and appear to be down-stream mediators of PTHrP signaling in the growth plate.Comment: In the growth plate, P...

To read the full abstract: Development 2018;145. pii:dev146829Branching morphogenesis is a key process during organogenesis of ductal and exocrine organs, e.g. lung, kidney, pancreas, and liver1. Regulatory components and local interactions for lung branching morphogenesis have been described in detail, mostly relying on receptor-ligand interactions between embryonic ...

To read the full abstract: J Endocr Soc 2017;1:1006-1011Besides its structural role in the extracellular matrix, aggrecan orchestrates a plethora of key mechanisms in endochondral ossification, such as embryonic morphogen distribution, regular indian hedgehog (IHH) / Sox9 expression and columnar chondrocyte orientation. Thus, homozygous loss-of-function mutations in the ACAN gene, encoding...

Premium research efforts, encompassing laboratory, translational, clinical studies and clinical trials, continually augment our understanding of skeletal biology, along with disorders associated with growth plate, bone, and mineral metabolism. This progression is currently offering innovative treatments for rare skeletal disorders. In this chapter, we underscore several promising clinical trials, notably: a phase 2 study investigating denosumab treatment for fibrous dysplasia,...

In Brief: Growth plate and articular cartilage have similar structures composed of distinct chondrocyte layers but they differ substantially with respect to their function and fate. This study combines transplantation experiments with cell tracing in rat with in vitrostudies to identify a novel mechanism by which synoviocytes act directly on chondrocytes to suppress endochondral and promote articular cartilage at the joint surface.Commentary: Gr...

In brief: This report describes the efficacy and safety of burosumab during the open-label extension period of the original Phase 3 study (weeks 64-88) in 21 children with X-linked hypophosphatemia (XLH) who continued to receive burosumab or crossed over from conventional therapy to burosumab.Commentary: X-linked hypophosphatemia (XLH) is a rare inherited disorder of phosphorus metabolism caused by loss-of-function mutations in the PHEX gene, re...