ISSN 1662-4009 (online)

ESPE Yearbook of Paediatric Endocrinology (2021) 18 5 | DOI: 10.1530/ey.18.5

1Division of Pediatric Endocrinology and Center for Molecular Medicine, Karolinska Institutet and University Hospital, Stockholm, Sweden; 2Department of Pediatrics and Adolescent Medicine, Medical University of Vienna, Vienna, Austria; 3Department of Pediatric Endocrinology, Royal Manchester Children’s Hospital, Manchester University NHS Foundation Trust, Manchester, UK; 4School of Medical Sciences, Örebro University and University Hospital, Örebro, Sweden.


The 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 antagonize the overactivity of the FGFR3 pathway in achondroplasia continues to be a subject of high interest and excitement and we here highlight the double-blind, randomized placebo-controlled phase 3 study of a CNP analogue (vosoritide) in children with achondroplasia. We also highlight the identification of a novel gene for autosomal dominant hypophosphatemic rickets, publication of new growth charts for X-linked hypophosphatemia and two large well-designed paediatric vitamin D trials for the prevention of tuberculosis and asthma exacerbation, respectively.

Translational highlights include an update on the current understanding and knowledge gaps in mineral metabolism and biomineralization, a Nature Medicine article presenting in vivo data suggesting that modification of the synovial microenvironment can allow endogenous skeletal stem cells to form hyalin cartilage and thereby heal articular cartilage injuries, as well as a study using gene targeting in zebra fish to reveal the pathogenic mechanism by which mutations in CRTAP and P3H1 causes osteogenesis imperfecta type VII and VIII, respectively.

In the section of skeletal biology, a study by McDonald et al., published in Cell, challenges the current dogma on the origin and fate of osteoclasts as they show evidence that multinucleated osteoclasts can fission into daughter cells, a.k.a. osteomorphs, that subsequently are recycled into bone resorbing osteoclasts via a RANKL-dependent process. Additional articles in this section directly and indirectly highlight the critical role of loading and mechanical stress on the growing skeleton. The findings by Hendrickx et al. indicates that mechano-sensing of growth plate chondrocytes is critical to bone formation in the secondary spongiosa. These findings in addition to Xie et al.’s findings that growth plates and especially hypertrophic chondrocytes are critically sensitive to mechanical stress and their hypothesis that secondary ossification centers have evolved to protect the growth plates are exciting and have direct implications to the discussion on the type of sport activities that should be recommended to growing children.

In addition, the chapter highlights several other important findings, including the high risk of hypoparathyroidism after total thyroidectomy in children, insights into the molecular mechanism by which PTHrP signalling prevents growth plate chondrocyte hypertrophy, as well as the critical role of Sox9 to prevent epiphyseal fusion and articular cartilage degeneration.

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