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Glucocorticoid (GC) therapy remains the cornerstone of treatment for many conditions of childhood and an important cause of skeletal and endocrine morbidity. Here, we discuss cases that bring to life the most important concepts in the management of pediatric GC-induced osteoporosis (pGIO). Given the wide variety of underlying conditions linked to pGIO, we focus on the fundamental clinical–biological principles that provide a blueprint for management in any clinical context. In so doing, we underscore the importance of longitudinal vertebral fracture phenotyping, how knowledge about the timing and risk of fractures influences monitoring, the role of bone mineral density in pGIO assessments, and the impact of growth-mediated "vertebral body reshaping" after spine fractures on the therapeutic approach. Overall, pGIO management is predicated upon early identification of fractures (including vertebral) in those at risk, and timely intervention when there is limited potential for spontaneous recovery. Even a single, low-trauma long bone or vertebral fracture can signal an osteoporotic event in an at-risk child. The most widely used treatments for pediatric osteoporosis, intravenous bisphosphonates, are currently recommended first-line for the treatment of pGIO. It is recognized, however, that even early identification of bone fragility, combined with timely introduction of the most potent bisphosphonate therapies, may not completely prevent osteoporosis progression in all contexts. Therefore, prevention of first-ever fractures in the highest-risk settings is on the horizon, where there is also a need to move beyond antiresorptives to the study of anabolic agents. [ABSTRACT FROM AUTHOR]

Context X-linked hypophosphatemia (XLH) is the most common form of inherited hypophosphatemic rickets (HR), caused by pathogenic variants in the PHEX gene. Genetic diagnosis of XLH facilitates early treatment optimization, especially for patients suitable for burosumab, a recombinant anti-fibroblast growth factor-23 monoclonal antibody. Objective This study aimed to use whole-exome sequencing (WES) and pedigree analysis to identify patients with XLH. Methods Medical records at a single center in Saudi Arabia were screened between 2014 and 2024 to identify patients with suggested HR. Of the 800 patients identified, 27 had had suspected XLH. The genetic study comprised 100 patients drawn from these 27 families. Results Clinical manifestations were widespread and variable within families. Severe disease was reported in 55% of children and 25% of adults. At presentation, all children were receiving either conventional therapy (60%) or burosumab (40%); however, 53% of adults were not treated. WES provided a genetic diagnosis in 23 families: alterations in the PHEX gene (20 families), with homozygous ENPP1 and DMP1 variants detected in 2 and 1 families, respectively. Pathogenic/likely pathogenic variants were detected in 23 families (diagnostic yield 85%). Ten novel likely pathogenic variants were detected. Pedigree analysis provided information to support disease-specific patient management. Conclusion WES detected a diagnostic molecular abnormality in 85% of families with HR phenotypes; PHEX variants were the most common. Combined use of WES and pedigree analysis highlighted the underdiagnosis of adult XLH in this population, with most family members being diagnosed after the pedigree analysis. [ABSTRACT FROM AUTHOR]

Context: X-linked hypophosphatemia (XLH) is the most common form of inherited hypophosphatemic rickets (HR), caused by pathogenic variants in the PHEX gene. Genetic diagnosis of XLH facilitates early treatment optimization, especially for patients suitable for burosumab, a recombinant anti-fibroblast growth factor-23 monoclonal antibody., Objective: This study aimed to use whole-exome sequencing (WES) and pedigree analysis to identify patients with XLH., Methods: Medical records at a single center in Saudi Arabia were screened between 2014 and 2024 to identify patients with suggested HR. Of the 800 patients identified, 27 had had suspected XLH. The genetic study comprised 100 patients drawn from these 27 families., Results: Clinical manifestations were widespread and variable within families. Severe disease was reported in 55% of children and 25% of adults. At presentation, all children were receiving either conventional therapy (60%) or burosumab (40%); however, 53% of adults were not treated. WES provided a genetic diagnosis in 23 families: alterations in the PHEX gene (20 families), with homozygous ENPP1 and DMP1 variants detected in 2 and 1 families, respectively. Pathogenic/likely pathogenic variants were detected in 23 families (diagnostic yield 85%). Ten novel likely pathogenic variants were detected. Pedigree analysis provided information to support disease-specific patient management., Conclusion: WES detected a diagnostic molecular abnormality in 85% of families with HR phenotypes; PHEX variants were the most common. Combined use of WES and pedigree analysis highlighted the underdiagnosis of adult XLH in this population, with most family members being diagnosed after the pedigree analysis., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society.)