Quantifying the material and structural determinants of bone strength

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746 M.L. Bouxsein, E. Seeman / Best Practice & Research Clinical Rheumatology 23 (2009) 741–753 ranelate is incorporated into the mineral substance of bone [86], it is not known whether these observations are true changes in bone morphology or artefacts due to altered edge-detection and/or partial volume effects. Altogether, HR-pQCT is promising for assessment of trabecular and cortical architecture in vivo with high precision. The disadvantages are that it requires specialised scanners, and measurements are limited to peripheral skeletal sites. Furthermore, motion artefacts are common, requiring re-scanning of many patients. Magnetic resonance imaging (MRI) Magnetic resonance (MR) imaging is a non-ionising method that uses a strong magnetic field in combination with specialised sequences of radio-frequency pulses to generate 3D images of bone structure [87]. Because free hydrogen in water provides the ‘signal’ in this type of MR imaging and since the water content of bone is minimal, there is generally little signal provided by bone in standard MR imaging. As a result, the bone structure is assessed indirectly via measurements of the surrounding marrow and other soft tissues (Fig. 4). Advances in the past decade have focussed on image acquisition and analysis techniques to overcome inherent obstacles in MR imaging of bone [88]. High-resolution MR imaging is performed at peripheral skeletal sites (e.g., distal radius, distal tibia and calcaneus) using clinical MR scanners combined with specially designed coils. In vivo resolutions of 150–300 mm in plane and a slice thickness of 300–500 mm have been achieved [89,90]. With this resolution, it is not possible to produce accurate values for most features of trabecular architecture. Nonetheless, the ‘apparent’ trabecular properties that are derived from these images correlate with trabecular architecture obtained with higher-resolution techniques [91,92]. Until recently, evaluation of trabecular bone morphology was limited to appendicular sites. However, innovative surface coils and pulse sequences show potential for MR-based assessments of trabecular structure in the proximal femur [93–95] (Fig. 5). MR-derived trabecular microarchitecture measurements reflect age- and disease-specific differences [96,97], and differentiate patients with hip and vertebral fractures from controls with the best performance achieved by combinations of structural parameters and BMD [98–103]. There are no studies demonstrating prospective fracture risk prediction, and there are limited data on treatmentrelated changes [104,105]. Fig. 4. Magnetic resonance image of the distal tibia (voxel size: 156 156 500 mm). Trabecular bone appears dark on a light background of marrow. Image courtesy of Dr. Sharmila Majumdar, UCSF.
M.L. Bouxsein, E. Seeman / Best Practice & Research Clinical Rheumatology 23 (2009) 741–753 747 Fig. 5. Magnetic resonance image of the proximal femur. Image courtesy of Dr. Sharmila Majumdar, UCSF. There are currently no non-invasive techniques available for clinical use that assess bone matrix properties, such as the degree of mineralisation, collagen content and/or the degree of collagen crosslinking. Yet, one particularly novel aspect of MRI is that it may allow non-invasive assessment of bone matrix properties in addition to bone structure. Solid-state MR imaging uses the resonant signals of the phosphorus ( [31] P) constituent of the bone mineral phase to determine the mineral content of bone [106–110]. Bone tissue mineral density measurements acquired through [31] P solid-state MR discriminate osteoporotic and osteomalacic animal models better than X-ray-based imaging methods [108]. Wu and colleagues[109] report that combined 31 P and 1 H water- and fat-suppressed solid-state imaging give MRI the unique ability to assess the organic and inorganic solid-phase densities of bone, as well as the solid bone matrix density (organic þ inorganic). Although 31 P solid-state MRI has been implemented in vivo with human subjects on a clinical 1.5 T system [111], solid-state MRI is still a research tool. Solid-state imaging may become an excellent tool for longitudinal bone tissue density evaluations (without consequence of radiation exposure), but currently, this method requires excessively long imaging times (w1 h or more), most studies have used non-clinical scanners with strong magnetic fields (4.7 T or greater) and custom-made coils. Thus, MRI is a non-ionising method that allows 3D assessment of cortical and trabecular bone structure. Image data can be acquired in any arbitrary axis with acquisition times of 10–15 min [88]. Finite element analysis (FEA) based on QCT- or hr-pQCT images The finite element (FE) method was first applied to structural analysis in the 1950s, and it has since been widely used in nearly every engineering and engineering-related field. In solid and structural mechanics (bone mechanics included), it is the method of choice for evaluating the how a structure with complex geometrical shape and heterogeneous distribution of material properties (e.g., a whole bone) behaves when subjected to external loads. The finite element approach begins by representing the object as a collection of building blocks, or elements, each of which is defined by reference points, or nodes. The FE method can provide ‘estimates’ of quantities that are commonly obtained through mechanical testing (e.g., whole bone stiffness and failure load), as well as quantities that are difficult, if not impossible, to measure experimentally (e.g., strain distribution). However, the ability of the finite element solution to approximate the actual biomechanical phenomenon depends on the quality of the input. For example, the choice of material
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