Predicting wrist osteoporosis from excised human finger bones using spatially offset Raman spectroscopy – a cadaveric study

Osteoporosis and osteopenia remain vastly underdiagnosed. Current clinical screening relies almost exclusively on dual-energy X-ray absorptiometry (DXA), which measures bone mineral density (BMD) but fails to capture the compositional changes that lead to BMD loss. We investigated whether spatially offset Raman spectroscopy (SORS) applied to excised finger bones can assess subsurface biochemical markers associated with bone health and estimate wrist DXA T-scores. Raman spectra were acquired <i>ex vivo</i> on the mid-shaft of the proximal phalanx of the second digit from 25 female cadavers spanning the three T-score categories (n = 8 normal, n = 6 osteopenic, and n = 11 osteoporotic) at spatial offsets of 0, 3, and 6 mm from a laser irradiation spot. After normalizing spectra to the PO₄ ^3- peak, group-averaged spectra of the three categories, measured at 3-mm offset, showed clear differences in the CO₃ ^2-, Amide III, CH₂, and Amide I bands. Quantitatively, four out of five mineral-to-matrix ratios discriminated (p ≤ 0.05) osteopenia from both normal and osteoporotic bone, and all five ratios showed significant differences between normal and osteoporotic bone. In contrast, the 0-mm offset showed reduced biochemical contrast in univariate analyses, while the 6-mm offset did not provide additional discrimination relative to 3-mm. Multivariate partial-least-squares regression (PLSR) models using 0-mm and 3-mm spectra predicted distal radius T-scores with comparable accuracy (Pearson r ≈ 0.90, RMSE_CV ≈ 0.8), but the 3-mm offset required fewer latent variables (1 vs. 9), consistent with the univariate analysis trends favoring 3-mm offset. These excised-bone findings justify future studies extending this approach to transcutaneous fingers for non-ionizing assessment of bone health.