Poster Presentation ESA-SRB-ANZBMS 2024 in conjunction with ENSA

Improvement in Bone Material Disorganization and Pseudofracture Healing Is Detectable Early after Initiation of Asfotase Alfa Therapy before changes in Bone Scintigraphy. (#390)

Roger Zebaze 1 , Cat Shore-Lorenti 1 , Frances Milat 1 2 , Peter R Ebeling 1
  1. Monash University, School of Clinical Sciences, Clayton, VIC, Australia
  2. Hudson Institute of Medical Research, Clayton, Vic, Australia

Background:  Hypophosphatasia (HPP) is a rare but serious genetic disease.  Quantification of the severity of bone disease in patients with HPP, monitoring HPP progress and response to therapy remain major unmet challenges.  Current bone biomarkers (density and architecture) are of limited value.  However, bone health is not solely determined by its mass, density or structure.  In addition, to these important features, each structural component must be in the right place (well-aligned, organized) (1).

 

In HPP, we propose that defective bone mineralization leads to an impaired ability to properly arrange (organized) bone.  Consequently, an effective therapy should improve bone disorganization.  We, therefore, hypothesized that measurement of the extent of bone disorganization provides a robust tool for assessing therapeutic effectiveness in patients with HPP.

 

Methods: In an 18-year-old female with benign prenatal HPP and with non-healing tibial pseudofracture, asfotase alfa was initiated.  Images (X-rays and bone scintigraphy) were collected at baseline, 03, 06, 12, 24 and 48 months (2).  Disorganization studies require a detailed analysis. Hence, each tibia was subdivided into 09 subregions. Disorganization values (DV) were quantified in each subregion using the ALIGNOGRAM Software (3).

 

Results:   On X-rays and Scintigraphy, signs of pseudofracture healing were detectable only after 06 months of treatment.  In contrast, after only 03 months, a marked improvement in bone disorganization (15.7%) was already detectable; with the median DV decreasing from 9.64 (IQR 9.56–9.91) to 8.1 (IQR 7.84–8.91) (p<0.001) (Figure, middle Panel).

 

Conclusion:  In this unique first-ever study, we report that measurement of disorganization allowed a robust and earliest (within 03 months) detection of the therapeutic effectiveness of Asfostase; before any improvement was visible on X-rays or bone scintigraphy.

 

This novel bone biomarker (Disorganization) that analyses standard readily available X-rays may open new and cheap ways of assessing patients with HPP and monitoring therapeutic response.

 

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