Oral Presentation 33rd ASM of the Australian & New Zealand Bone & Mineral Society 2023

Bone Disorganization:  A Novel Biomarker Unrelated to Bone Density and Structure that May Hold the Key to The Diagnosis of Atypical, Stress Fractures, and Other Unexplained Bone Diseases.   (#55)

Roger Zebaze 1 , Cat Shore-Lorenti 1 , Cherie Chiang 2 , Hanh Nguyen 1 , Simon Zheng 1 , Kevin Djopseu 3 , Tessa Makebeh 3 , Frances Milat 4 , Peter Ebeling 1
  1. Monash University, School of Clinical Sciences, Clayton, VIC, Australia
  2. Endocrinology and Medicine, Austin Health, Heidelberg, VIC
  3. ZEZE co, Yaounde
  4. Hudson Institute of Medical Research, Clayton, Vic, Australia

64b911e44589b-Figure_AFF+Abstract_2023_RZ+et+al.pngBackground–The cause of many bone diseases and fractures remains a mystery. To address this enigma, we recently proposed that the abnormality in these patients is an incorrect arrangement (or disorganization) of an otherwise sufficient or even high amount of bone which by abnormally transferring loads cause damage; triggering inflammation, and a vicious cascade of events leading to diseases including fractures1. Hence, we developed and validated a tool to quantify this novel biomarker (disorganization)2.  Here, we test the hypothesis that measures of disorganization are unrelated BMD or decay, YET identifies patients with diseases such as Atypical Femoral Fractures (AFFs), Paget Disease of Bone (PDB), and Hypophosphatasia (HPP).

 

Methods–We studied 45 women (10 AFFs and fracture-free peers) mean(SEM) age 68.1(1.83) years. In addition, we studied patients PDBs(02) and HPPs(02).  Curves displaying the extent disorganization along the femoral shaft(ALIGNOGRAM) were produced. Metrics of disorganization metrics were quantified as previously reported2. Correlations between disorganization metrics, bone structure, and density were assessed.

 

Results– In normal subjects, ALIGNOGRAMs were relatively flat, regular with low Disorganization values (DVs); no abrupt or striking peaks. In all patients with AFFs, PDBs, and HPPs ALIGNOGRAMs were irregular, chaotic with higher DVs and spike-shaped peaks corresponding to the most disorganized sites within the bones (Fig 1).   The mean DV (MDV) distinguished AFFs from controls [36.3 (IQR 23.9-60.8) vs 3139 (IQR 1212-14788)]; p<0.0001. However, the MDV was not correlated with lateral and medial cortical thicknesses, or periosteal diameter (All R2<0.001; NS).  The MDV was also unrelated to density (R2=0.0002; p=0.17).

 

Conclusion– Disorganization is a novel mechanism and biomarker completely unrelated to bone mass and microarchitecture. This novel biomarker, readily quantifiable from standard X-rays, may hold the key to the identification of fractures that occur in individuals without reduced bone density or structural decay such as AFFs, HPP or PDB.

  1. 1. Zebaze R, Ebeling PR. Disorganization and Musculoskeletal Diseases: Novel Insights into the Enigma of Unexplained Bone Abnormalities and Fragility Fractures. Curr Osteoporos Rep. 2022 Dec 10. doi: 10.1007/s11914-022-00759-2. 2. Zebaze R, Shore-Lorenti C, Nguyen HH, Chiang C, Milat F, Ebeling PR. A Quantification Method for Disorganized Bone Components: Application to the Femoral Shaft. JBMR Plus. 2023;7(2):e10713.