What is drug-induced rickets?

Answer

Different medications may affect bone in different ways. Chronic anticonvulsant therapy (particularly with phenobarbital and phenytoin) may cause rickets, regardless of appropriate vitamin D intake. The main mechanism is related to induction of hepatic cytochrome P-450 hydroxylation, generating inactive metabolites. Levels of 25-hydroxyvitamin D₃ were reported to be low in children on long-term anticonvulsant therapy.

Fractures were associated with the use of anticonvulsants in patients with cerebral palsy.^[7]A down-regulation of 25-hydroxylation by phenobarbital may explain, at least in part, the increased risk of osteomalacia, bone loss, and fractures associated with long-term phenobarbital therapy.^[8]Conversely, calcitriol levels in plasma are reportedly not low in patients taking medication for seizures.

The dose of vitamin D required to prevent this type of rickets is unclear. Supplementation may not be needed. Approximately 800-1000 IU/day, plus good calcium intake, may be sufficient.

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Media Gallery

Radiograph in a 4-year-old girl with rickets depicts bowing of the legs caused by loading.
Findings in patients with rickets.

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Author

Horacio B Plotkin, MD, FAAP Chief Medical Officer, Retrophin, Inc; Adjunct Associate Professor of Pediatrics and Orthopedic Surgery, University of Nebraska College of Medicine

Horacio B Plotkin, MD, FAAP is a member of the following medical societies: American Academy of Pediatrics

Disclosure: Received salary from PPD, Inc for: PPD.

Coauthor(s)

Laurence Finberg, MD Clinical Professor, Department of Pediatrics, University of California, San Francisco, School of Medicine and Stanford University School of Medicine

Laurence Finberg, MD is a member of the following medical societies: American Medical Association

Disclosure: Nothing to disclose.

Chief Editor

Jatinder Bhatia, MBBS, FAAP Professor of Pediatrics, Medical College of Georgia, Georgia Regents University; Chief, Division of Neonatology, Director, Fellowship Program in Neonatal-Perinatal Medicine, Director, Transport/ECMO/Nutrition, Vice Chair, Clinical Research, Department of Pediatrics, Children's Hospital of Georgia

Jatinder Bhatia, MBBS, FAAP is a member of the following medical societies: Academy of Nutrition and Dietetics, American Academy of Pediatrics, American Association for the Advancement of Science, American Pediatric Society, American Society for Nutrition, American Society for Parenteral and Enteral Nutrition, Society for Pediatric Research, Southern Society for Pediatric Research

Disclosure: Serve(d) as a director, officer, partner, employee, advisor, consultant or trustee for: Nestle<br/>Serve(d) as a speaker or a member of a speakers bureau for: Nestle<br/>Received income in an amount equal to or greater than $250 from: Nestle.

Acknowledgements

Maria Rebello Mascarenhas, MBBS Associate Professor of Pediatrics, University of Pennsylvania School of Medicine; Section Chief Nutrition, Division of Gastroenterology and Nutrition, Director, Nutrition Support Service, Children's Hospital of Philadelphia

Maria Rebello Mascarenhas, MBBS is a member of the following medical societies: American Gastroenterological Association, American Society for Parenteral and Enteral Nutrition, and North American Society for Pediatric Gastroenterology and Nutrition

Disclosure: Nothing to disclose.

Mary L Windle, PharmD Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

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