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DISCUSSION


The aim of this project was to develop an algorithm which allows simulation of the response of the trabecular bone in age­related bone loss and to determine the biomechanical consequences of such a response based on realistic three­dimensional models of the trabecular microstructure Two groups of seven trabecular bone specimens were measured micro-tomographically including specimens from pre­menopausal and post­menopausal women respectively. In order to control bone loss over time, a novel algorithm to simulate bone resorption and adaptive processes was developed. Although the simulations were computationally very intensive, minimal user interaction was needed to build and analyse the models. All individual steps were fully automated. The algorithm, also referred to as simulated bone atrophy (SIBA), generated a set of microstructural models, iteratively derived from the original three-dimensional structure. Simulated bone atrophy was used to "age-match" the first and the second group incorporating an underlaying realistic time-frame for the simulation. Using quantitative bone morphometry and three-dimensional animation tools, the changes in bone density and bone architecture could be monitored over a average observation time of 43 years. The structures at the end-point of the simulations were then compared qualitatively and quantitatively to the structure of the post-menopausal group. In general, good correspondence was found between the two groups. Differences on the order of 10% can easily be accounted for given the huge biological variations of up to 50% in the different structural properties of trabecular bone as seen in the analysis of the BIOMED I study [1]. Although there are several limitations to this study, we believe that we were able to demonstrate that it is possible to simulate, at least certain aspects, of age-related bone loss using the proposed mechanism. The implemented approach in combination with micro-structural trabecular bone models allowed a successful transformation of "young-and-normal" to "old-and-osteopenic" bone on a microstructural level. Another advantage of the proposed model was that an identical remodeling law and time step was applied to both iliac and lumbar trabecular bone, which raises the question whether there is a universal law for all types of bone with respect to the effects on the cellular level. One of the limitations of simulated bone atrophy is that at the moment no experimental data is available to backup the proposed cellular mechanisms and that no mechanical feedback loop is included in the algorithm. This is especially important for simulation of bone modeling related to osteogenesis or fracture healing in healthy subject with the ability to react to such changes in the overall loading patterns. For this reason, one of the future goals must be a combination of load and hormone driven modeling and remodeling on a microstructural level. Nevertheless, it might well be that to describe the effects purely associated with age-related bone loss in a hormone deficiency model, where bone seems to have at least partly lost its ability to adapt to alterations in its mechanical environment, load-driven modeling and remodeling might not have that much of an importance anymore.

To our knowledge, this is the first time that age-related bone loss has been described and simulated directly based on three-dimensional measurements of trabecular bone with the incorporation of a realistic time-frame. Because it is the first time, discussion of the results is difficult. Nevertheless, validation will be of crucial importance for further application of simulated bone atrophy. The only way to really validate any remodeling theory would be the incorporation of in vivo follow-up measurements providing not only important experimental data on the time-scale and structural properties of atrophied bone but also allowing validation of each remodeling step in the simulation. Kinney et al. [2] developed a CT­scanning method demonstrating sequential changes in bone structure at a resolution of a few microns. However, this resolution is only possible in animal experiments due to dose considerations. Since we are interested in the prediction of the individual fracture risk of patients, the final aim must be the non­invasive assessment of the bone architecture in human subjects in vivo. In order to assess the structural changes in the progress of rapid bone loss, Müller et al. [3] introduced a method to assess and analyse cancellous bone based upon three-dimensional peripheral computed tomography in vivo. In their study, structural parameters could be reproduced in vivo with a coefficient of variation of less than 0.5% demonstrating the potential of high­resolution tomography to detect structural changes in trabecular bone during age-related bone loss or therapeutic and diagnostic trials. The nominal resolution provided by the system was 170 µm, which would not be sufficient for validation purposes. However, we strongly believe that in the future it will be possible to assess architectural information from in vivo follow­up measurements providing a resolution high enough to allow simulations of bone adaptation with the possibility to non­invasively follow bone remodeling and adaptation in vivo. This will allow to make assumptions for a more realistic time­scale of remodeling processes on an individual basis.

One of the future goals of the project will be to investigate the consequences of bone atrophy on the mechanical behavior of the trabecular bone over time. Generally, the influence of the microstructural adaptation on the biomechanical competence of the bone can be expressed as a function of its anisotropic bone properties on the continuum level. Recently, it has been shown that the mechanical properties of trabecular bone can be predicted using microstructural large-scale finite element analyses [4-6]. The application of such simulations in combination with FEA of non­destructively assessed trabecular bone structures will help to understand the influence of age-related bone loss on the mechanical behavior of trabecular bone and will also be used to validate similar findings from follow­up patient measurements in vivo.

References:

  1. R. Müller and P. Rüegsegger, "Micro­tomographic imaging for the nondestructive evaluation of trabecular bone architecture", Bone Research in Biomechanics, G. Lowet, P. Rüegsegger, H. Weinans, A. Meunier (eds.), pp. 61­79, IOS Press, Amsterdam, 1997.
  2. J. H. Kinney, N. E. Lane, and D. L. Haupt, "In vivo, three­dimensional microscopy of trabecular bone", J. Bone Min. Res. 10, pp. 264­270, 1995.
  3. R. Müller, T. Hildebrand, H. J. Häuselmann, and P. Rüegsegger, "In vivo reproducibility of three­dimensional structural properties of noninvasive bone biopsies using 3D­pQCT", J. Bone Min. Res. 11, pp. 1745­1750, 1996.
  4. B. Van Rietbergen, H. Weinans, R. Huiskes, and A. Odgaard, "A new method to determine trabecular bone elastic properties and loading using micromechanical finite­element models", J. Biomech. 28, pp. 69­81, 1995.
  5. R. Müller and P. Rüegsegger, "Three­dimensional finite element modeling of non­invasively assessed trabecular bone structures", J. Med. Eng. Phys. 17, pp. 126­133, 1995.
  6. D. Ulrich, T. Hildebrand, B. Van Rietbergen, R. Müller, and P. Rüegsegger, "The quality of trabecular bone evaluated with micro­computed tomography, FEA and mechanical testing", Bone Research in Biomechanics, G. Lowet, P.Rüegsegger, H. Weinans, A. Meunier (eds.), pp. 97­112, IOS Press, Amsterdam, 1997.

Ralph Müller · ESB'98 · Toulouse · 2-8 July 1998