Decreased Compressional Sound Velocity Is an Indicator for Compromised Bone Stiffness in X-Linked Hypophosphatemic Rickets (XLH)

Abstract

Objectives: To assess the diagnostic potential of bidirectional axial transmission (BDAT) ultrasound, and high-resolution peripheral quantitative computed tomography (HR-pQCT) in X-linked hypophosphatemia (XLH, OMIM #307800), a rare genetic disorder of phosphate metabolism caused by mutations in the PHEX gene.Methods: BDAT bone ultrasound was performed at the non-dominant distal radius (33% relative to distal head) and the central left tibia (50%) in eight XLH patients aged between 4.2 and 20.8 years and compared to twenty-nine healthy controls aged between 5.8 and 22.4 years. In eighteen controls, only radius measurements were performed. Four patients and four controls opted to participate in HR-pQCT scanning of the ultradistal radius and tibia.Results: Bone ultrasound was feasible in patients and controls as young as 4 years of age. The velocity of the first arriving signal (ν FAS ) in BDAT ultrasound was significantly lower in XLH patients compared to healthy controls: In the radius, mean ν FAS of XLH patients and controls was 3599 ± 106 and 3866 ± 142 m/s, respectively (−6.9%; p < 0.001). In the tibia, it was 3578 ± 129 and 3762 ± 124 m/s, respectively (−4.9%; p = 0.006). HR-pQCT showed a higher trabecular thickness in the tibia of XLH patients (+16.7%; p = 0.021).Conclusions: Quantitative bone ultrasound revealed significant differences in cortical bone quality of young XLH patients as compared to controls. 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 patients.

Consensus Recommendations for the Diagnosis and Management of X-Linked Hypophosphatemia in Belgium

“…Although low Z- or T-scores may point to other diagnoses such as HHRH/NPHLOP or TIR/TIO, DXA is not recommended in the work-up nor in the follow-up of XLH. Bone ultrasound and high-resolution quantitative computed tomography have also shown increased cortical and trabecular bone mass in XLH patients, although these techniques are still considered investigational ( 100 ) and not clinically useful.…”

Defining a Growing and Maturing Skeleton and its Relevance in Diseases that Affect Skeletal Growth, Such as X-Linked Hypophosphataemia (XLH)

“…Trabecular thickness in the tibia was significantly higher in the patients with XLH compared with the control groups. In addition, cortical thickness in the tibia showed a tendency to be higher in patients with XLH compared with the control groups [74].…”

“…Bidirectional axial transmission (BDAT) bone ultrasound of the radius and tibia of children and young adults with XLH aged between 4.2 and 20.8 years revealed a poorer bone quality in terms of matrix stiffness and strength compared with healthy controls [74]. Trabecular thickness in the tibia was significantly higher in the patients with XLH compared with the control groups.…”

Potential influences on optimizing long-term musculoskeletal health in children and adolescents with X-linked hypophosphatemia (XLH)

“…Studies using dual-energy X-ray absorptiometry (DXA) in patients with XLH also suggest that bone mineral density (BMD) is increased at the spine, but not at cortical sites [ 45 ]. DXA is a two-dimensional measurement of a three-dimensional structure that only reflects BMD and does not provide information on compartment-specific BMD and bone quality [ 46 , 47 ]. Additional calcifications and enthesopathy may also influence these measurements, with resultant artefactual increases, and therefore DXA should be interpreted with caution in patients with XLH.…”