Raman spectroscopy detects deterioration in biomechanical properties of bone in a glucocorticoid-treated mouse model of rheumatoid arthritis

Abstract

Abstract. Although glucocorticoids are frequently prescribed for the symptomatic management of inflammatory disorders such as rheumatoid arthritis, extended glucocorticoid exposure is the leading cause of physician-induced osteoporosis and leaves patients at a high risk of fracture. To study the biochemical effects of glucocorticoid exposure and how they might affect biomechanical properties of the bone, Raman spectra were acquired from ex vivo tibiae of glucocorticoid-and placebo-treated wild-type mice and a transgenic mouse model of rheumatoid arthritis. Statistically significant spectral differences were observed due to both treatment regimen and mouse genotype. These differences are attributed to changes in the overall bone mineral composition, as well as the degree of phosphate mineralization in tibial cortical bone. In addition, partial least squares regression was used to generate a Raman-based prediction of each tibia's biomechanical strength as quantified by a torsion test. The Raman-based predictions were as accurate as those produced by microcomputed tomography derived parameters, and more accurate than the clinically-used parameter of bone mineral density. These results suggest that Raman spectroscopy could be a valuable tool for monitoring bone biochemistry in studies of bone diseases such as osteoporosis, including tests of drugs being developed to combat these diseases. C 2011 Society of Photo-Optical Instrumentation Engineers (SPIE).

Polarization control of Raman spectroscopy optimizes the assessment of bone tissue

“…RS sensitivity to glucocorticoid-treatment in rheumatoid arthritis bone shows compositional difference despite normalization to Amide I when using a fiber optic (polarization insensitive) system. 26 These biomechanical correlations are likely separate and distinct from RS correlations to collagen tension changes seen in formal polarization analysis. 36 Given low instrument polarization and results from less polarization sensitive carbonate and Amide III bands, analysis of bone from osteoarthritic patients on different load bearing surfaces can be interpreted as a largely compositional effect.…”

“…Spectra were then binned to a resolution of 3 cm −1 , and processed via least squares modified polynomial fit 39 and smoothed for noise using an 2nd order Savitsky-Golay filter. 26,40 After fluorescence subtraction, a linear baseline subtraction (based on derivative zero-crossings neighboring the peak) was conducted on peaks that overlap with other constituents to ensure no residual fluorescence, namely Proline, Hydroxyproline, ν1 Phosphate, and Carbonate. Spatial resolution for each objective used was approximated via edge detection on a polished silicon standard.…”

“…25 On the other hand, strength of bone from vehicle-and glucocorticoid-treated mice was correlated to various RS peaks when normalized to Amide I in a fiber optic system. 26 Despite differences in modes of biomechanical testing among these studies, the polarization state of the instrument likely influences which RS biomarkers are sensitive to experimental groups.…”

Raman spectroscopy: techniques and applications in the life sciences

“…PLS can also be trained to predict non-chemical properties of the sample. For example, Maher et al used PLS and Raman spectroscopy to measure bone strength [502] and Duraipandian et al estimated the probability of future development of cancer [503].…”

Co-localized confocal Raman spectroscopy and optical coherence tomography (CRS-OCT) for depth-resolved analyte detection in tissue

“…For instance, optical coherence tomography (OCT) can measure depth-resolved tissue morphology up to one millimeter below the tissue surface [3,4] depending upon the type of tissue and its associated optical properties. Chemically-sensitive optical methods, such as Raman spectroscopy (RS) [5][6][7][8][9][10][11], can measure spatiotemporal distributions of analytes with up to micron-level spatial resolution when utilizing confocal detection [12]. In fact, confocal Raman spectroscopy has been recently applied, using commercially-available instrumentation, to detect Tenofovir in tissue samples ex vivo [13].…”