Cortical and trabecular bone density in X-linked hypophosphatemic rickets

Area of Science:

• Bone Metabolism and Genetics
• Pediatric Endocrinology
• Skeletal Radiology

Background:

• X-linked hypophosphatemic rickets (XLH) is a genetic disorder caused by mutations in the PHEX gene.
• XLH is characterized by impaired skeletal mineralization, but detailed bone densitometry data are limited.
• Understanding bone density in XLH is crucial for assessing disease severity and treatment efficacy.

Purpose of the Study:

• To evaluate volumetric bone mineral density (vBMD) in patients with X-linked hypophosphatemic rickets.
• To utilize forearm peripheral quantitative computed tomography (pQCT) for precise vBMD assessment.
• To investigate the impact of PHEX mutations on trabecular and cortical bone density.

Main Methods:

• The study included 34 patients with PHEX mutations, aged 6 to 60 years.
• Peripheral quantitative computed tomography (pQCT) was used to measure trabecular and cortical vBMD of the radius.
• Patients were categorized based on current treatment status: actively treated, previously treated, or never treated.

Main Results:

• Overall, patients exhibited elevated trabecular vBMD (z-score +1.0), significantly higher in those actively treated (z-score +2.4).
• Cortical vBMD was generally low (z-score -3.3), with higher values in actively treated patients (z-score -1.3) compared to untreated groups.
• Active treatment correlated with better, though still reduced, cortical vBMD compared to discontinued or never-treated patients.

Conclusions:

• Patients with PHEX mutations demonstrate elevated trabecular vBMD and reduced cortical vBMD at the distal radius.
• Calcitriol and phosphate supplementation appear to increase trabecular vBMD but only partially improve cortical vBMD.
• The persistent low cortical vBMD suggests that current treatments do not fully resolve the underlying mineralization defect in XLH.