Osteoporosis is a disease of increased risk for bone fracture that is associated with low bone mass. Fractures in patients with osteoporosis commonly occur in the spine, hip, or wrist, and often cause pain and loss of mobility. Bisphosphonates are effective in preventing osteoporotic fractures and preventing bone loss. However, recently, there is concern that long-term treatment with bisphosphonates may be associated with rare cases of atypical fracture—fractures that occur at sites such as the femoral shaft that are uncommon for typical osteoporotic fractures, which are not caused by trauma and are unable to heal. Some patients have suppressed bone remodeling as evidenced by histomorphometry. While the pathogenesis of atypical fractures is poorly understood, there may be changes in the quality of the bone tissue that are associated with atypical fracture. The focus of this dissertation was to characterize the bone tissue-level mechanical properties of atypical fracture patients with severely suppressed bone turnover (SSBT).

We analyzed the intrinsic tissue properties of iliac bone biopsy specimens taken from SSBT patients (aged 49-77) , age-matched osteoporotic patients with vertebral fracture, age-matched normal subjects, and young subjects (aged 20-40) using nanoindentation. Backscattered electron microscopy was used to characterize the tissue mineral densities of bone tissues. Finite element models were developed using backscattered electron microscopy images to analyze the cracking behavior of bone tissues from fracture and non-fracture groups.

SSBT patients had cortical and trabecular bone tissue with greater plastic deformation resistance than osteoporotic patients and normal subjects. The trabecular bone of SSBT patients also had greater elastic modulus, contact hardness, and a trend of greater mineral density than the comparison groups, which is consistent with properties of advanced tissue age. The variability in cortical bone elastic modulus was lower in SSBT bone tissue compared to that of the other groups, which may indicate a lessened ability to prevent crack propagation. Tissue mineral density was a poor predictor of mechanical properties at the microscopic scale, indicating that the collagen matrix may contribute significantly to the determination of bone mechanical properties at the microscopic level. Cracking outcomes were not different among the groups when predicted using the computational model, but the cracks in SSBT bone may be more detrimental that those in normal bone due to the inhibited repair mechanisms in the former. In our model, bone tissue with greater variability in elastic properties had smaller cracks, indicating that heterogeneity may be protective of crack propagation.

In summary, we found that the bone quality of patients with atypical fractures with suppressed bone turnover differed from that of untreated vertebral fracture patients and non-fracture controls. Greater plastic deformation resistance properties in SSBT compared to controls may be associated with an increased risk for atypical fracture and the brittle nature of the fracture. Tissue mineral density changes indicate more aged tissue, and accumulation of cracks due to suppressed remodeling may contribute to fracture. These results support the hypothesis that atypical fractures are associated with changed hard tissue properties.