Background: X-linked hypophosphatemia (XLH) is a rare genetic disorder of phosphate metabolism caused by mutations in the PHEX gene. XLH patients exhibit short stature and skeletal deformities, which are caused by defective bone mineralization site leading to increased porosity and decreased matrix stiffness. Bone mineral density measurements have been shown to be insensitive to the cumulative bone alterations. The velocity of the first arriving signal (vFAS) measured in bi-directional axial transmission (BDAT) is determined by cortical thickness, cortical porosity and matrix stiffness. Therefore, we hypothesized that ultrasound may be a potential alternative to quantify the onset and severity of the disease.
Methods: Following study approval by institutional review and written informed consent, we performed quantitative bone ultrasound in children, adolescents and young adults with XLH (N=8) and healthy controls (N = 13). A sub-group majority of patients (n = 4) and controls (n = 4) also underwent high-resolution peripheral quantitative computed tomography (HR-pQCT) of the ultra-distal radius and tibia. Bone ultrasound was performed at the distal radius and the central distal tibia according to a structured examination protocol, using a certified BDAT system (Althais, France) equipped with a 1.2 MHz linear transducer array with 2 x 5 transmit elements and a central 24 element receiver array. The velocity of the first arriving signal (vFAS) was determined from 100 measurement cycles at each measurement location. HR-pQCT images were reviewed by a board-certified radiologist, cortical and trabecular parameters were evaluated using the manufacturer's software.
Results: BDAT measurements were conducted successfully in all study participants. The velocity of the first arriving signal (VFAS) in BDAT ultrasound was significantly lower in XLH patients compared to healthy controls: In the radius, mean VFAS of XLH patients and controls was 3553 ± 196 and 3873 ± 143 m/s, respectively (-8.3 %; P < 0.001). In the tibia, it was 3531 ± 156 and 3757 ± 119 m/s, respectively (-6.0 %; P = 0.019). HR-pQCT revealed a slightly increased trabecular thickness in XLH patients (XLH: 0.07 mm, controls: 0.06 mm, P = 0.02).
Discussion and Conclusion: These preliminary results suggest that sound velocity is a suitable indicator for XLH associated bone alterations. Regular monitoring of XLH patients by a radiation-free technology such as BDAT might provide valuable information on bone quality and contribute to the optimization of treatment. Further studies are needed to establish this affordable and time efficient method in the XLH patient cohort.
19 - 21 Sep 2019
European Society for Paediatric Endocrinology