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Rickets

Nature Reviews Disease Primers volume 3, Article number: 17101 (2017) | Download Citation

Abstract

Rickets is a bone disease associated with abnormal serum calcium and phosphate levels. The clinical presentation is heterogeneous and depends on the age of onset and pathogenesis but includes bowing deformities of the legs, short stature and widening of joints. The disorder can be caused by nutritional deficiencies or genetic defects. Mutations in genes encoding proteins involved in vitamin D metabolism or action, fibroblast growth factor 23 (FGF23) production or degradation, renal phosphate handling or bone mineralization have been identified. The prevalence of nutritional rickets has substantially declined compared with the prevalence 200 years ago, but the condition has been re-emerging even in some well-resourced countries; prematurely born infants or breastfed infants who have dark skin types are particularly at risk. Diagnosis is usually established by medical history, physical examination, biochemical tests and radiography. Prevention is possible only for nutritional rickets and includes supplementation or food fortification with calcium and vitamin D either alone or in combination with sunlight exposure. Treatment of typical nutritional rickets includes calcium and/or vitamin D supplementation, although instances infrequently occur in which phosphate repletion may be necessary. Management of heritable types of rickets associated with defects in vitamin D metabolism or activation involves the administration of vitamin D metabolites. Oral phosphate supplementation is usually indicated for FGF23-independent phosphopenic rickets, whereas the conventional treatment of FGF23-dependent types of rickets includes a combination of phosphate and activated vitamin D; an anti-FGF23 antibody has shown promising results and is under further study.

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Affiliations

  1. Department of Pediatrics (Endocrinology), School of Medicine, Yale University, PO Box 208064, New Haven, Connecticut 06520–8064, USA.

    • Thomas O. Carpenter
  2. Department of Endocrinology & Diabetes, Birmingham Children's Hospital, Birmingham, UK.

    • Nick J. Shaw
  3. Institute of Metabolism and Systems Research, University of Birmingham, Birmingham, UK.

    • Nick J. Shaw
  4. Department of Pediatrics, University of California, San Francisco, California, USA.

    • Anthony A. Portale
  5. Department of Pediatrics, University of Ottawa, Ottawa, Ontario, Canada.

    • Leanne M. Ward
  6. Department of Pediatrics, Dell Medical School at the University of Texas-Austin, Austin, Texas, USA.

    • Steven A. Abrams
  7. South African Medical Research Council–Wits Developmental Pathways for Health Research Unit, Department of Paediatrics, Faculty of Health Sciences, University of the Witwatersrand, 7 York Road, Parktown, Johannesburg 2194, South Africa.

    • John M. Pettifor

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Contributions

Introduction (T.O.C. and J.M.P.); Epidemiology (L.M.W. and S.A.A.); Mechanisms/pathophysiology (T.O.C., J.M.P., A.A.P. and S.A.A.); Diagnosis, screening and prevention (N.J.S.); Management (T.O.C. and J.M.P.); Quality of life (L.M.W.); Outlook (A.A.P.); Overview of Primer (T.O.C. and J.M.P.).

Competing interests

T.O.C. is a consultant for and is participating in clinical trials of burosumab with Ultragenyx Pharmaceutical and has served as a consultant for Alexion. A.A.P. has received honoraria from and is participating in a clinical trial of burosumab with Ultragenyx Pharmaceutical. L.M.W. has received honoraria from and is participating in a clinical trial of burosumab with Ultragenyx Pharmaceutical and has been a consultant to Alexion. J.M.P. is a consultant for Biomedical Systems Corporation. N.J.S. and S.A.A. declare no competing interests.

Corresponding authors

Correspondence to Thomas O. Carpenter or John M. Pettifor.

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https://doi.org/10.1038/nrdp.2017.101

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