Title:Diagnostic and New Therapeutic Approaches to Two Challenging
Pediatric Metabolic Bone Disorders: Hypophosphatasia and X-linked
Hypophosphatemic Rickets
Volume: 20
Issue: 4
Author(s): Fahad Aljuraibah*, Ibrahim Alalwan and Abdelhadi Habeb
Affiliation:
- Department of Pediatrics, King Abdullah Specialist Children’s Hospital, King Abdulaziz Medical City, Ministry of National
Guard Health Affairs, Riyadh, Saudi Arabia
- College of Medicine, King Saud bin Abdul-Aziz University for
Health Sciences, Ministry of National Guard Health Affairs, Riyadh, Saudi Arabia
- King Abdullah International Medical
Research Center, Ministry of National Guard Health Affairs Riyadh, Saudi Arabia
Keywords:
Metabolic bone disorders, hypophosphatasia, X-linked hypophosphatemic rickets, monoclonal anti-FGF23 antibody, skeletal mineralization, secondary skeletal dysplasia, renal osteodystrophy .
Abstract: The diagnosis and management of metabolic bone disease among children can be challenging.
This difficulty could be due to many factors, including limited awareness of these rare
conditions, the complex pathophysiology of calcium and phosphate homeostasis, the overlapping
phenotype with more common disorders (such as rickets), and the lack of specific treatments for
these rare disorders. As a result, affected individuals could experience delayed diagnosis or misdiagnosis,
leading to improper management. In this review, we describe the challenges facing diagnostic
and therapeutic approaches to two metabolic bone disorders (MBD) among children: hypophosphatasia
(HPP) and X-linked hypophosphatemia (XLH). We focus on explaining the pathophysiological
processes that conceptually underpin novel therapeutic approaches, as well as these
conditions’ clinical or radiological similarity to nutritional rickets. Particularly in areas with limited
sun exposure and among patients not supplementing vitamin D, nutritional rickets are still
more common than HPP and XLH, and pediatricians and primary physicians frequently encounter
this disorder in their practices. More recently, our understanding of these disorders has significantly
improved, leading to the development of novel therapies. Asfotas alfa, a recombinant, human-
tissue, nonspecific alkaline phosphatase, improved the survival of patients with HPP. Burosumab,
a human monoclonal anti-FGF23 antibody, was recently approved as a specific therapy for
XLH. We also highlight the current evidence on these two specific therapies’ safety and effectiveness,
though long-term data are still needed. Both HPP and XLH are multisystemic disorders that
should be managed by multidisciplinary teams. Finally, recognizing these conditions in early
stages will enable affected children and young adults to benefit from newly introduced, specific
therapies.
