Raman microspectroscopy for study of genetic and metabolic disorders of bone tissue.

Abstract

We used Raman spectroscopy to examine chemical composition of bone in two diseases, osteogenesis imperfecta and osteoporosis, representing genetic and metabolic disorder of the bone respectively. The chemical properties as well as trends in the chemical alterations caused by the diseases were obtained. In a study of fracture susceptibility in osteoporosis, we showed that femoral head of fracture specimens had a higher carbonate-to-phosphate ratio than controls. Investigation of tissue from a different anatomical location, the iliac crest, showed similar changes in bone mineral. Our interpretation is that differences in mineral composition report changes in trabecular bone architecture that are correlated with fracture risk. In a study of the Brtl mouse models of osteogenesis imperfecta, we observed changes both in the mineral crystallinity and in collagen structure. We observed reduced mineral crystallinity in the heterozygous mouse. In the homozygous mouse, we confirmed the observed disulfide collagen crosslinks and found near-normal mineral crystallinity. Blunt guillotine fractures on mouse tibia were used to show that chemical composition changes were caused by tissue failure, independent of any local abnormalities that might weaken the tissue. We have observed changes in the carbonate-to-phosphate and phosphate-to-amide III ratios, within ∼ 300 gm of the fracture front but not at longer distances from the damage site. Overall, this dissertation explores possible Raman makers that are indicative of chemical composition changes associated with bone diseases and concluded that there is potentially unique information that can be used in evaluation of bone health.