A Quantification Method for Disorganized Bone Components: Application to the Femoral Shaft

Area of Science:

• Orthopedics and Bone Biology
• Medical Imaging and Diagnostics
• Biomarker Discovery

Background:

• Bone health is traditionally defined by mass and microarchitecture, but component organization is crucial for structural integrity.
• Bone disorganization is implicated in various skeletal abnormalities, including osteogenesis imperfecta, hypophosphatasia, and atypical femur fractures (AFFs).
• Current methods lack tools to quantify bone disorganization in vivo, representing a significant unmet clinical need.

Purpose of the Study:

• To develop and validate a novel method for quantifying bone disorganization using X-ray images.
• To assess the utility of this disorganization biomarker in identifying patients at risk for fractures, particularly those with AFFs.
• To explore the role of bone disorganization as an independent contributor to bone abnormalities beyond bone mineral density (BMD) and microarchitecture.

Main Methods:

• A novel method was developed to quantify bone disorganization by measuring variations in bone component orientation relative to a reference point.
• The method's accuracy was validated against a 'gold standard' using artificially disarranged bone pixels.
• Disorganization levels were compared in femurs from women with AFFs, fracture-free contralateral femurs, and fracture-free control femurs.

Main Results:

• The developed method demonstrated excellent agreement with the 'gold standard' (R² values 0.84–0.99) and high precision (1.72%–4.69% error).
• Significantly increasing levels of bone disorganization were observed in femurs with AFFs, followed by contralateral femurs, and then control femurs (p < 0.0001).
• The quantification of disorganization accurately captured abnormalities associated with AFFs.

Conclusions:

• Quantification of bone disorganization from X-ray images is a feasible and accurate novel biomarker.
• Bone disorganization is a significant factor in bone fragility and fracture risk, especially in conditions like AFFs.
• This novel biomarker offers insights into bone pathogenesis beyond traditional BMD and microarchitecture assessments, aiding in fracture risk stratification.