Prediction of biomechanical properties of ex vivo human femoral cortical bone using Raman spectroscopy and machine learning algorithms

This study applied Raman spectroscopy (RS) to ex vivo human cadaveric femoral mid-diaphysis cortical bone specimens (<i>n</i> = 118 donors; age range 21-101 years) to predict fracture toughness properties via machine learning (ML) models. Spectral features, together with demographic variables (age, sex) and structural parameters (cortical porosity, volumetric bone mineral density), were fed into support vector regression (SVR), extreme tree regression (ETR), extreme gradient boosting (XGB), and ensemble models to predict fracture-toughness metrics such as crack-initiation toughness (K_init) and energy-to-fracture (J-integral). Feature selection was based on Raman-derived mineral and organic matrix parameters, such as ν₁Phosphate (PO₄)/CH₂-wag, ν₁PO₄/Amide I, and others, to capture the complex composition of bone. Our results indicate that ensemble models consistently outperformed individual models, with the best performance for crack initiation toughness (K_init) prediction being achieved using the ensemble approach. This yielded a coefficient of determination (R²) of 0.623, root-mean squared error (RMSE) of 1.320, mean absolute error (MAE) of 1.015, and mean percentage absolute error (MAPE) of 0.134. For prediction of the overall energy to propagate a crack (J-integral), the XGB model achieved an R² of 0.737, RMSE of 2.634, MAE of 2.283, and MAPE of 0.240. This study highlights the importance of incorporating mineral quality properties (MP) and organic matrix properties (OMP) for enhanced prediction accuracy. This work represents the first-ever study combining Raman spectroscopy with other clinical and structural features to predict fracture toughness of human cortical bone, demonstrating the potential of artificial intelligence (AI) and ML in advancing bone research. Future studies could focus on larger datasets and more advanced modeling techniques to further improve predictive capabilities.