Hypophosphatemia and Excess FGF23: Are They Causing Your Patient’s Bone Pain and Other Issues?

Hypophosphatemia and Excess FGF23: Are They Causing Your Patient’s Bone Pain and Other Issues?

Med-IQ Select
Released: 5/19/2021
Expires: 5/18/2022
Max Credits: 1.0
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Thomas O. Carpenter, MD
Professor of Pediatrics (Endocrinology)
Professor of Orthopaedics and Rehabilitation
Director, Yale Center for X-Linked Hypophosphatemia
Yale School of Medicine
New Haven, CT

Anthony A. Portale, MD
Professor, Department of Pediatrics
Division of Pediatric Nephrology
Benioff Children’s Hospital
University of California, San Francisco
San Francisco, CA

Activity Planners
Iwona Misiuta, PhD, MHA
Clinical Content Manager
Baltimore, MD

Rebecca L. Julian, MS, ELS
Senior Manager, Editorial
Baltimore, MD

Samantha Gordon, MS
Accreditation Manager 
Baltimore, MD

Amy Sison
Director of CME
Baltimore, MD 

Katherine Kahn
Holyoke, MA

Learning Objectives
Upon completion, participants should be able to:

  • Integrate the current evidence regarding the diagnosis of hereditary and acquired forms of hypophosphatemia related to excess FGF23
  • Identify the benefits and limitations associated with medical therapies for the management of hypophosphatemia related to excess FGF23, specifically XLH and TIO, in adults, adolescents, and children

Target Audience
This activity is intended for family physicians, rheumatologists, and endocrinologists practicing in the United States and Canada, as well as nephrologists, internal medicine specialists, pediatricians, nurses, and pharmacists practicing in the United States and Canada who manage patients with hypophosphatemia.
Statement of Need
X-linked hypophosphatemia (XLH) and tumor-induced osteomalacia (TIO) are two rare conditions attributed to hereditary and acquired forms of chronic hypophosphatemia, respectively, that are caused by excess levels of fibroblast growth factor 23 (FGF23). Both conditions are frequently misdiagnosed and subsequently mismanaged in adults, adolescents, and children due to their rarity, varying presentations, and nonspecific symptoms. Physicians, patients, and support groups have noted that a previous lack of treatment guidelines for XLH has also contributed to misdiagnosis and mismanagement. Research over the past 15 years has led to a greater understanding of phosphate metabolism, specifically the role of excess FGF23 and its contributions to renal phosphate wasting and chronic hypophosphatemia, and to the first FDA-approved and FGF23-targeted therapy for both XLH and TIO. To appropriately identify patients who may benefit from this therapy, clinicians need to recognize the symptoms of hereditary and acquired forms of hypophosphatemia early on and be familiar with the risks and benefits associated with current management strategies for patients with XLH and TIO.

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Provided by Med-IQ.

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Med-IQ is accredited by the Accreditation Council for Continuing Medical Education (ACCME) to provide continuing medical education for physicians.  

Med-IQ designates this enduring material for a maximum of 1.0 AMA PRA Category 1 Credit™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Nurse practitioners, physician assistants, and other healthcare professionals who successfully complete the activity will receive a Statement of Participation indicating the maximum credits available.
Medium/Method of Participation
This is a 1.0-credit CE activity. To receive credit, read the introductory CE material, complete all of the modules, and complete the evaluation, attestation, and post-test, answering at least 70% of the post-test questions correctly. 

Initial Release Date: May 19, 2021
Expiration Date: May 18, 2022
Estimated Time to Complete This Activity: 1 hour

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Off-label/unapproved drug uses or products are mentioned within this activity. 

Disclosure Statement
The content of this activity has been peer reviewed and has been approved for compliance. The faculty and contributors have indicated the following financial relationships, which have been resolved through an established COI resolution process, and have stated that these reported relationships will not have any impact on their ability to give an unbiased presentation.

Thomas O. Carpenter, MD
Consulting fees/advisory boards: Inozyme Pharma, Kyowa Kirin, Ultragenyx Pharmaceutical Inc.
Contracted research: Ultragenyx Pharmaceutical Inc.

Anthony A. Portale, MD
Fees received for promotional/non-CME activities: Ultragenyx Pharmaceutical Inc.
Contracted research: Ultragenyx Pharmaceutical Inc.
The writer, peer reviewers, and activity planners have no financial relationships to disclose.
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Complimentary CE
This activity is available free of charge to participants.

Acknowledgment of Commercial Support
This activity is supported by an educational grant from Ultragenyx Pharmaceutical Inc.


Here are the key takeaways from this activity. Deeper insights and evidence, plus an opportunity to receive credit, are available at the "Continue" button below.

  • Several causes of FGF23-mediated hypophosphatemia have been identified, including XLH, ADHR, ARHR, FD in MAS, CSHS, and TIO
  • Children with XLH usually develop clinical manifestations by 1 to 2 years of age that include rachitic skeletal deformities, impaired growth, delayed walking (during their second year), and dental abscesses (usually at age > 3 years); biochemical abnormalities are often evident by the third month of life, and radiographic abnormalities are evident by the second year of life
  • XLH symptoms and clinical abnormalities that present in childhood persist into adulthood and often include leg deformities, bone pain, gait abnormalities, short stature, muscle pain/weakness, fatigue, osteomalacia, fractures and pseudofractures, dental abscesses, tooth loss, and mild secondary hyperparathyroidism
  • In TIO, when a tumor cannot be identified or is unresectable or only partially resectable, the next options include pharmacologic intervention with either oral administration of 1,25(OH)2D and phosphate or a human monoclonal antibody that directly inhibits excess FGF23 activity
  • Medical therapy for XLH and TIO has historically consisted of oral administration of active vitamin D analogues (eg, calcitriol, alfacalcidol) and phosphate salts; however, burosumab, a recombinant human monoclonal antibody that directly inhibits excess FGF23 activity, was recently approved for the treatment of XLH in adults and children 6 months of age and older and for the treatment of TIO in individuals 2 years of age and older

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