Abstract

Dual X-ray absorptiometry (DEXA) is the current gold standard for the diagnosis of osteoporosis. However, patients can suffer osteoporotic fractures despite normal bone mineral density, partly because of unmeasured influences of both the protein and mineral phases of bone that are affected in osteoporosis. There is currently no clinically applicable method of evaluating the health of the protein phase. The proteins in human nail (keratin) and bone (collagen) require sulphation and disulphide bond (S-S) formation for structural integrity and disorders of either sulphur metabolism or cystathione beta-synthase can lead to structural abnormalities in these tissues. Raman protein spectra provide a method of non-invasive measurement of the degree of sulphation of structurally related proteins that may be indicative of bone health. Raman spectroscopy was used to evaluate the disulphide (S-S) content of fingernails. The nail samples came from from 169 women (84 pre- and 85 post-menopausal), of which 39 had a history of osteoporotic fracture. BMD was measured by DXA at the spine. Analyses included parametric and non-parametric tests, dependent on the distribution of the test variable. Mean disulphide content of the nail reduced with age and was slightly higher in pre-, compared to post-menopausal women (P = 0.187). Significantly lower disulphide content was observed in nails obtained from subjects with a history of fracture (P = 0.025). When either disulphide content or BMD was used as a predictor, the odds ratio of these two measures were found to be comparable predictors for fracture status. This suggests that measurements of change in the protein phase of structural proteins such as keratin in the human nail may be correlated with clinically relevant changes in bone proteins that are important in fracture risk.

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