Towards the in vivo prediction of fragility fractures with Raman spectroscopy

Abstract

Fragility fractures, those fractures which result from low level trauma, have a large and growing socio‐economic cost in countries with aging populations. Bone‐density‐based assessment techniques are vital for identifying populations that are at higher risk of fracture, but do not have high sensitivity when it comes to identifying individuals who will go on to have their first fragility fracture. We are developing Spatially Offset Raman Spectroscopy (SORS) as a tool for retrieving chemical information from bone non‐invasively in vivo. Unlike X‐ray‐based techniques SORS can retrieve chemical information from both the mineral and protein phases of the bone. This may enable better discrimination between those who will or will not go on to have a fragility fracture because both phases contribute to bone's mechanical properties. In this study we analyse excised bone with Raman spectroscopy and multivariate analysis, and then attempt to look for similar Raman signals in vivo using SORS. We show in the excised work that on average, bone fragments from the necks of fractured femora are more mineralised (by 5–10%) than (cadaveric) non‐fractured controls, but the mineralisation distributions of the two cohorts are largely overlapped. In our in vivo measurements, we observe similar, but as yet statistically underpowered, differences. After the SORS data (the first SORS measurements reported of healthy and diseased human cohorts), we identify methodological developments which will be used to improve the statistical significance of future experiments and may eventually lead to more sensitive prediction of fragility fractures. © 2015 The Authors. Journal of Raman Spectroscopy Published by John Wiley & Sons, Ltd.

Raman spectroscopy: techniques and applications in the life sciences

“…This is possible as hydroxyapatite (HA) is a major mineral component of bone, and contains a strong Raman peak at 962 cm −1 due to a phosphate mode which is used as a sub-layer indicator, whilst collagen peaks are typically used to identify the surface layer. These measurements were initially carried out on animals and cadavers [391], but have since progressed to preliminary trials for in-vivo measurements of bone-disease monitoring for fracture risk prediction [407].…”

Feasibility of Spatially Offset Raman Spectroscopy for in Vitro and in Vivo Monitoring Mineralization of Bone Tissue Engineering Scaffolds

“…SORS allowed the measurement of subsurface chemical information in diffusely scattering samples, typically from depths of 20 µm -5 mm range, which is beyond the reach of confocal RS. Furthermore, SORS has been used for in-vivo transcutaneous measurements of bone quality in small animals 22,23 and humans 24,25 .…”

Assessment of photon migration for subsurface probing in selected types of bone using spatially offset Raman spectroscopy

“…Transcutaneous bone characterization using SORS to identify potential markers for bone disease is currently a very active research area. [2][3][4][5] The bone volume probed by SORS is dependent on photon scattering inside the specimen, which is determined by its optical properties. Initial photon migration investigations on cortical bone have been conducted by our group to assess the effects of different spatial offsets on the interrogated sample depth.…”