Evaluation of Raman Spectroscopy for Fracture Resistance Assessment

Abstract

The age-related risk of skeletal fracture is a significant problem in modern medicine, such that both hip fracture and osteoporotic fracture are listed in the World Health Organization top 12 sources of disease burden, with nearly 9 million osteoporotic fractures in the year 2000 alone. Dual energy X-ray absorptiometry or (DXA) is the clinical “gold standard” in the diagnosis of fracture risk for disease like osteoporosis. However, DXA based assessment of areal bone mineral density does not explain the age related increase in fracture risk. Despite the excellence in advances of X-ray based technologies and complementary etiological factors (FRAX), the DXA method is fundamentally limited to the assessment of the mineral phase of bone. Therefore growing efforts to improve fracture risk assessment have led to the development of several complementary tools to analyze bone quality beyond its mineral density. At the core of this interchange between laboratory science and clinical diagnosis, Raman Spectroscopy (RS) has become a critical tool for measuring bone composition. The stable chemical composition and crystalline nature of bone tissue makes RS a powerful tool suited for the needs of bone assessment. Despite significant work in identifying the RS features of bone tissue, little evidence correlates RS to fracture resistance of bone. This thesis focuses on the evaluation of RS as a clinically relevant tool for bone fracture resistance assessment. I will detail how I established the technique of manipulating light polarization to concurrently measure both the organization and composition of bone according to optical theory, despite the complications of biological tissue. Application of the methods will show how RS measures of organization explain bone brittleness when measures of composition do not. Finally, I will detail how multivariate expressions of RS describing the interplay between organization and composition led to the first nondestructive explanation of fracture toughness in the largest human sample study to date. The analysis reveals that fracture toughness is driven by microstructural heterogeneity and not bulk composition, with significant implications for our understanding of clinical fracture resistance and future designs applications of RS instruments to material quality.