Raman spectroscopy as a tool for monitoring osteoporosis therapy in postmenopausal osteoporosis

Bisphosphonate-based pharmacological therapy of osteoporosis reduces risk of fracture, but modulation of bone mineral density does not solely explain this. Additional bone quality aspects affecting fragility need to be better understood, alongside methods to monitor them. Systemic factors that influence bone collagen remodelling also remodel keratin in parallel processes. In this study, human fingernail clippings from subjects with and without bone active pharmaceutical intervention are compared. A discriminant model was able to distinguish between the nails from patients that were treatment-naive and treated with an area under the curve of 71% in the test set. A time series of changes relative to baseline revealed that after 1 year, the scores of the treated group (95 confidence interval 37% to 377% change) differed from both the 12 week measurements (-198% to 34%) and scores from untreated subjects (-92% to -674%). Analysis of the spectral differences and model coefficients revealed features that were inverse to those observed in three previous osteoporosis models, indicating that treatment was reverting damaged protein structure. This study provides preliminary evidence that bone active medication systemically influences keratin structure in humans and provides some discussion on the underlying mechanism. The study demonstrates that bisphosphonates have a direct influence on protein structure, warranting further investigation of these effects. Bone active medication systemically influences keratin structure in humans. Model based on Raman spectra of human fingernails can discriminate between treated and untreated individuals. Model is correlated with previous models of osteoporosis. Over time, untreated individuals show a trend suggestive of increasing osteoporosis risk, whereas treated individuals show a reversal suggesting lowering of risk.image