Bone Material Quality at Osteoporotic Fractures

Osteoporotic femoral neck fractures are becoming a socioeconomic important cause of morbidity and mortality in the elderly. In women an osteoporotic hip bone is defined by a mineral density level of more than 2.5 standard deviations (SD) below the mean of young, adult women (T-score -2.5). However, the bone density (BMD) of the femoral neck do not determine the fracture risk alone, hence, these T-scores do not really provide a good basis for establishing general diagnostic thresholds. Consequently, it can result in misclassification and or unnecessary therapies. In principle, three structural levels might be involved in the deterioration of the mechanical properties of the femoral neck: 1) the amount of bone material, 2) the bone architecture and 3) the quality of the bone material. Up to now no comprehensive study, where all the three aspects were simultaneously evaluated has been performed. However, for targeting preventative care, methods have to be found, which enable to predict fracture risk more precisely. In close collaboration with the Medical Department at the Cambridge University (Dr. J. Reeve and Dr. N. Loveridge), the relation between osteoporotic femoral neck fractures and alterations of bone properties at all three structural levels mentioned above will be studied. For this purpose femoral neck bone samples from normal individuals (autopsies, n=12) and cases of osteoporotic femoral neck fractures (n>12), will be determined by: a) quantitative backscattered electron imaging (qBEI) for the quantification of the calcium concentration distribution, b) polarized light microscopy (pLM) to visualize the main collagen orientation of the lamellar bone. c) scanning- SAXS to characterize the collagen/mineral nanocomposite material of bone, d) nanoindentation by the AFM for the assessment of E-modulus and hardness of bone, e) three point bending tests of small compact bone specimens (3.0x0.5x0.5 mm). Finally, the data obtained by qBEI, pLM, scanning-SAXS and AFM will be correlated with the data revealed by the methods applied in Cambridge: Peripheral quantitative computed tomography (pQCT), histology of biopsy cross-sections including assessment of osteocytes and insitu biochemistry for alkaline phosphatase and acid phosphatase New insights in structural changes of bone caused by osteoporosis and its relation to increased fracture incidence can be expected These findings will provide the basis for new strategies of osteoporosis prevention and treatment.

Osteoporotic femoral neck fractures are becoming a socioeconomic important cause of morbidity and mortality in the elderly. In women an osteoporotic hip bone is defined by a mineral density level of more than 2.5 standard deviations (SD) below the mean of young, adult women (T-score -2.5). However, the bone density (BMD) of the femoral neck do not determine the fracture risk alone, hence, these T-scores do not really provide a good basis for establishing general diagnostic thresholds. Consequently, it can result in misclassification and or unnecessary therapies. In principle, three structural levels might be involved in the deterioration of the mechanical properties of the femoral neck: 1) the amount of bone material, 2) the bone architecture and 3) the quality of the bone material. Up to now no comprehensive study, where all the three aspects were simultaneously evaluated has been performed. However, for targeting preventative care, methods have to be found, which enable to predict fracture risk more precisely. In close collaboration with the Medical Department at the Cambridge University (Dr. J. Reeve and Dr. N. Loveridge), the relation between osteoporotic femoral neck fractures and alterations of bone properties at all three structural levels mentioned above will be studied. For this purpose femoral neck bone samples from normal individuals (autopsies, n=12) and cases of osteoporotic femoral neck fractures (n>12), will be determined by: a) quantitative backscattered electron imaging (qBEI) for the quantification of the calcium concentration distribution, b) polarized light microscopy (pLM) to visualize the main collagen orientation of the lamellar bone. c) scanning- SAXS to characterize the collagen/mineral nanocomposite material of bone, d) nanoindentation by the AFM for the assessment of E-modulus and hardness of bone, e) three point bending tests of small compact bone specimens (3.0x0.5x0.5 mm). Finally, the data obtained by qBEI, pLM, scanning-SAXS and AFM will be correlated with the data revealed by the methods applied in Cambridge: Peripheral quantitative computed tomography (pQCT), histology of biopsy cross-sections including assessment of osteocytes and insitu biochemistry for alkaline phosphatase and acid phosphatase New insights in structural changes of bone caused by osteoporosis and its relation to increased fracture incidence can be expected These findings will provide the basis for new strategies of osteoporosis prevention and treatment.