Improvements in Bone Disorganization and Pseudo‐Fracture Healing in Hypophosphatasia Following Asfotase Alfa Therapy May Be Detectable by the ALIGNOGRAM Before Changes in Bone Radiography or Scintigraphy

Hypophosphatasia (HPP) is a rare genetic disorder characterized by bone fragility due to defective bone mineralization resulting in impaired alignment of bone components (bone disorganization). Current challenges in the management of HPP include accurately quantifying bone disease severity, monitoring disease progression, and assessing treatment response, particularly in pseudo-fracture healing. Conventional tools such as bone mineral density (BMD) and architecture assessments do not adequately address these issues as they do not assess bone disorganization, limiting their utility in HPP. In this study, we use the ALIGNOGRAM software to reanalyze pseudo-fracture healing in a previously presented case report of an 18-year-old female with benign HPP treated with asfotase alfa. We show that improvements in bone disorganization were detectable as early as 3 months after treatment initiation-before changes on X-ray or bone scintigraphy were detected. As such, assessment of the degree of bone disorganization could serve as an early indicator of treatment efficacy in HPP.