Development and validation of novel image-based bone strength measures

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Osteoporosis is defined as a skeletal disorder characterized by compromised bone strength predisposing to an increased risk of fracture. Wrist fractures of the distal radius are the most common fractures in older women and early indicators of future osteoporotic fracture risk. Wrist fracture occurs when the external forces applied to bone—usually due to fall-related impact—exceeds whole bone strength. Whole bone strength can only be directly determined via destructive mechanical testing ex vivo. However, surrogate measures of bone structure and material properties can be used to estimate bone strength in vivo, and are commonly obtained by medical imaging and computational micro-finite element (microFE) modeling. Peripheral quantitative computed tomography (pQCT) images of distal radius structure and material properties offer unique potential to estimate bone strength in vivo. Standard pQCT can be used to calculate strength indices to estimate whole bone strength using engineering-based beam theory. However, commonly used bone strength indices have only been validated at the tibia (our previous work), not the fracture-prone distal radius. High resolution pQCT (HR-pQCT) images, with small (82 micron) isotropic voxels, provide detailed information of bone microarchitecture and when combined with microFE modeling, have been used to estimates failure load of the whole or excised sections of distal radius undergoing axial compressive loading. A common limitation in these strength estimates is that they have been validated in mechanical testing scenarios involving axial compression only. Loading conditions experienced during a fall on the outstretched hand, though, include a combination of axial compression and “off-axis” dorsal- and lateral-directed forces which create bending. It is unknown how to best predict bone strength resisting off-axis loading. The primary objective of this research program is to develop and validate pQCT, HR-pQCT and microFE imaging methods to estimate distal radius bone strength under combined axial compression and off-axis loading. We will first scan distal radii of 15 female cadaver arms with both pQCT and HR-pQCT scanners using standard imaging protocols. We will then mechanically test specimens in novel off-axis loading conditions and validate the new pQCT-derived strength indices and HR-pQCT microFE-derived failure load against mechanical properties (failure load, strain). The secondary objective, using a swine model, is to develop validated pQCT-derived muscle composition assessments. Information from this research program will add to the fundamental understanding of bone strength under combination of axial compression and off-axis loading. Validated muscle outcomes will complement future models of fracture risk assessment. Findings will be important for skeletal research, prevention and treatment of osteoporotic wrist fractures.