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.
