Machine learning reconstruction of digit bone Raman spectra enables noninvasive transcutaneous detection of systemic osteoporosis
Osteoporosis, a major global epidemic, often goes undetected until a fracture occurs, largely due to poor access to screening using gold standard methods, such as dual-energy X-ray absorptiometry (DXA). As a potential nonionizing radiation alternative, we present a transcutaneous spatially offset Raman spectroscopy (SORS) approach combined with machine learning (ML) to recover bone spectra through overlying soft tissue and extract diagnostic information. In a human cadaveric study spanning normal, osteopenic, and osteoporotic donors, we acquired paired Raman measurements from transcutaneous fingers at multiple spatial offsets (0, 3, and 6 mm) and from the corresponding exposed finger bones. Using this paired dataset, supervised machine-learning models were trained to reconstruct exposed-bone Raman spectra from transcutaneous measurements, enabling direct recovery of bone biochemical signatures from transcutaneous tissue. The ML predicted bone spectra preserved physiologically meaningful Raman features and demonstrated statistically significant differences between normal and osteoporotic groups across four key Raman-derived metrics (p < 0.05), representing, to our knowledge, the first demonstration of transcutaneous Raman discrimination between clinically established bone-health categories in a human cadaveric study. The ML-predicted spectra further correlated with distal-radius DXA T-scores (r = 0.73, RMSECV = 1.4), approaching the performance achieved using exposed-bone measurements (r = 0.9, RMSECV = 0.8). Finally, preliminary in vivo measurements from two volunteers revealed clear bone-related transcutaneous spectral features consistent with cadaveric data, supporting translational feasibility. Together, these results establish a foundation for nonionizing radiation, transcutaneous Raman assessment of bone health using supervised spectral extraction from accessible measurement sites