In integrative biomedical research, methods assessing the clinical or even socio-economic impact of more complex technologies such as Information and Communication Technology (ICT)-based tools for modelling and simulation of human physiology have rarely been applied. The EU funded Osteoporotic Virtual Physiological Human (VPHOP) research project, part of the Virtual Physiological Human (VPH) European initiative, will create a patient-specific hypermodel to predict the absolute risk of bone fracture much more accurately than predictions based on current clinical practice. The project has developed an innovative, multilevel generic methodological framework to assess the clinical and socio-economic impact of biocomputational models. The assessment framework consists of three components: a socio-economic cost benefit analysis, health economic analysis of care pathways, and disease cost simulation models. Through its holistic perspective, the method provides a tool to appraise the overall value of biocomputational models for society.
|Lippuner, K., et al., FRAX(R) assessment of osteoporotic fracture probability in Switzerland. Osteoporos Int, 2009 (2009)|
|Cristofolini, L., et al., Strain distribution in the proximal human femoral metaphysis. Proc Inst Mech Eng H, 2009. 223(3): p. 273-88 (2009)|
|Lenaerts, L. and G.H. van Lenthe, Multi-level patient-specific modelling of the proximal femur. A promising tool to quantify the effect of osteoporosis treatment. Philosophical Transactions of the Royal Society A, 2009. 367: p. 2079-2093 (2009)|
|Taddei, F., et al., Tibia adaptation after fibula harvesting: an in vivo quantitative study. Clin Orthop Relat Res, 2009. 467(8): p. 2149-58 (2009)|
|Thiel, R., Stroetmann, K. A., Stroetmann, V. N., Viceconti, M., 2009. Designing a socio-economic assessment method for integrative biomedical research: the Osteoporotic Virtual Physiological Human project. Stud Health Technol Inform 150, 876-80 (2009) View|
|Chevalley, T., et al., Deleterious effect of late menarche on distal tibia microstructure in healthy 20-year-old and premenopausal middle-aged women. J Bone Miner Res, 2009. 24(1): p. 144-52 (2009)|
|P. A. Hulme, S. K. Boyd, P. F. Heini and S. J. Ferguson. Differences in endplate deformation of the adjacent and augmented vertebra following cement augmentation. Journal Eur Spine J, 2009. 18: p. 614-623 (2009)|
|Gerhard, F.A., et al., In silico biology of bone modelling and remodelling - Adaptation. Philosophical Transactions of the Royal Society A, 2009. 367: p. 2011-2030 (2009)|
|Lippuner, K., et al., Remaining lifetime and absolute 10-year probabilities of osteoporotic fracture in Swiss men and women. Osteoporos Int, 2009. 20(7): p. 1131-40 (2009)|
|Mueller, T.L., et al., Non-invasive bone monitoring by high-resolution pQCT: A reproducibility study on structural and mechanical properties at the human radius. Bone, 2009. 44: p. 364-371 (2009)|
|Beraudi, A., Stea, S., Bordini, B., Baleani, M., Viceconti, M., 2010. Osteon classification in human fibular shaft by circularly polarized light. Cells Tissues Organs 191(3), 260-8 (2010) View|
Pattern of osteonal classification referred to collagen fiber orientation in a human fibula was studied. Along the length of the whole bone, serial 100-microm parallel cross sections were obtained and analyzed by circularly polarized light microscopy. The distribution of 3 different kinds of osteons (transversal, alternated and longitudinal-hooped) depending on their collagen fiber orientation were analyzed to determine the effect of length, anatomical quadrant and cortical thickness. Referring to length, the 3 types of osteons appeared with approximately the same relative frequency, but when the symmetry of the fibula was considered and the length was expressed as distance from the bone mid-section, the alternated osteons are predominant in the mid-section. On the contrary, moving toward the epiphyses, the balance is inverted, and transversal together with longitudinal-hooped types become more frequent than the alternated type. Osteonal pattern distribution was not significantly affected by the anatomical quadrant of each section or by the thickness of the cortex. This observation seems to confirm that along the fibula shaft the orientation of collagen fibers within the osteons is consistent with the loading conditions which the bone undergoes. 2009 S. Karger AG, Basel.
|Zwierzak, I., Baleani, M., Viceconti, M., 2009. Microindentation on cortical human bone: effects of tissue condition and indentation location on hardness values. Proc Inst Mech Eng H 223(7), 913-8 (2009) View|
The hardness of cortical human bone has been measured on osteons in different conditions. However, no data are reported in the literature regarding the effect of cortical tissue condition and indentation location on the measured hardness values. This study aimed to investigate whether the hardness of the human cortical bone evaluated by micro-indentation is influenced, first, by the tissue condition and, second, by the distance of the indentation from the edge of the Haversian canal. Two femura were collected from a subject without musculoskeletal disease. The Vickers hardness was measured by means of microindentation (applied load, 100 gf) on osteons with a cross-section greater than 200 microm. The tests were performed on wet and embedded tissue at different distances from the Haversian canal edge (30-150 microm). No significant differences were found in hardness values between the two contralateral femura. Embedded tissue was significantly harder (12 per cent) than wet tissue. No significant differences were found in hardness values measured at different distances from the Haversian canal edge except for those closer than 60 microm. Therefore, indentations cannot be performed on osteons small in cross-section, since the distance from the closer pore has to be controlled. They should be performed on wet tissue, to avoid an offset in the measured hardness.
|Cristofolini, L., et al., Multiscale investigation of the functional properties of the human femur. Philos Transact A Math Phys Eng Sci, 2008. 366(1879): p. 3319-41 (2008)|
|Guilley, E., et al., Reversal of the hip fracture secular trend is related to a decrease in the incidence in institution-dwelling elderly women. Osteoporos Int, 2008. 19(12): p. 1741-7 (2008)|
|Hijlkema, S., Osteoporose en biomechanica: het osteoporose-interview, in Osteoporose Journaal. 2008, DCHG: Haarlem. p. 2-5 (2008)|
|Hunter, P., et al., Meeting Report on the 2nd MEI International Symposium - The Worldwide Challenge to Physiome and Systems Biology and Osaka Accord. J Physiol Sci, 2008. 58(7): p. 425-31 (2008)|
|Kohl, P., et al., The virtual physiological human. Editorial. Philos Transact A Math Phys Eng Sci, 2008. 366(1879): p. 3223-4 (2008)|
|Rizzoli, R., Nutrition: its role in bone health. Best Pract Res Clin Endocrinol Metab, 2008. 22(5): p. 813-29 (2008)|
|Taddei, F., et al., A new meshless approach for subject-specific strain prediction in long bones: Evaluation of accuracy. Clin Biomech (Bristol, Avon), 2008. 23(9): p. 1192-9 (2008)|
|van Lenthe, G.H., et al., Quantification of bone structural parameters and mechanical competence at the distal radius. J. Orthop. Trauma, 2008. 22(8 Suppl.): p. S66-S72 (2008)|
|Viceconti, M., G. Clapworthy, and S. Van Sint Jan, The Virtual Physiological Human - a European initiative for in silico human modelling. J Physiol Sci, 2008. 58(7): p. 441-6 (2008)|
|Webster, D.J., et al., A novel in vivo model for mechanically stimulated bone adaptation - a combined experimental and computational study. Comp. Meth. Biomech. and Biomed. Eng., 2008. 11(5): p. 435-441 (2008)|
|Clapworthy, G., et al., The virtual physiological human: building a framework for computational biomedicine I. Editorial. Philos Transact A Math Phys Eng Sci, 2008. 366(1878): p. 2975-8 (2008)|
|Kriemler, S., et al., Weight-bearing bones are more sensitive to physical exercise in boys than in girls during pre- and early puberty: a cross-sectional study. Osteoporos Int, 2008. 19(12): p. 1749-58 (2008) View|
We carried out a cross-section study of the sex-specific relationship between bone mineral content and physical activity at sites with different loading in pre- and early pubertal girls and boys. There was significant sensitivity of bone mineral content of the hip to physical exercise in boys, but not in girls. BACKGROUND: Since little is known whether there are sex differences in sensitivity of bone to loading, we investigated sex differences in the cross-sectional association between measures of physical activity (PA) and bone mass and size in pre- and early pubertal children of both sexes. METHODS: We measured bone mineral content/density (BMC/BMD) and fat-free mass (FFM) in 269 6- to 13-year-old children from randomly selected schools by dual-energy X-ray absorptiometry. Physical activity (PA) was measured by accelerometers and lower extremity strength by a jump-and-reach test. RESULTS: Boys (n = 128) had higher hip and total body BMC and BMD, higher FFM, higher muscle strength and were more physically active than girls (n = 141). Total hip BMC was positively associated with time spent in total and vigorous PA in boys (r = 0.20-0.33, p < 0.01), but not in girls (r = 0.02-0.04, p = ns), even after adjusting for FFM and strength. While boys and girls in the lowest tertile of vigorous PA (22 min/day) did not differ in hip BMC (15.62 vs 15.52 g), boys in the highest tertile (72 min/day) had significantly higher values than the corresponding girls (16.84 vs 15.71 g, p < 0.05). CONCLUSIONS: Sex differences in BMC during pre- and early puberty may be related to a different sensitivity of bone to physical loading, irrespective of muscle mass.
|Tassani, S., Ohman, C., Baleani, M., Baruffaldi, F., Viceconti, M., 2010. Anisotropy and inhomogeneity of the trabecular structure can describe the mechanical strength of osteoarthritic cancellous bone. J Biomech (2010) View|
Osteoarthritic cancellous bone was studied to investigate the development of this pathology, and the functional changes it induces in the bone. In order to predict how the morphological alterations of the tissue induced by the pathology can change the mechanical properties of the structure, two different strategies have been used in the literature: (1) emphasising the influence of structural anisotropy; (2) stressing the highly inhomogeneous characteristics of cancellous bone. The aim of the present study was to verify the theory that mechanical strength of osteoarthritic cancellous bone depends both on tissue anisotropy and inhomogeneity. Twenty-five specimens were extracted from osteoarthritic femoral heads, along selected directions, and analysed by means of a microtomograph. The same specimens were mechanically tested in compression to determine the mechanical strength. The most representative structural parameters, confirmed by a stepwise analysis, were used to define four models to describe the measured mechanical strength. The models were applied neglecting (global analysis) or considering (local analysis) tissue inhomogeneities to verify whether the correlation with ultimate stress could be improved. The coefficient of determination increased from 0.53, considering only bone volume fraction, up to 0.88, combining it with off-axis angle and normalised eigenvalue. A further improvement was found performing a local analysis (R(2)=0.90), which corresponded to a decrease of 17% in the residual error. The proposed approach of considering both tissue anisotropy and inhomogeneity improved the accuracy in predicting the mechanical behaviour of cancellous bone tissue and should be suitable for more general loading conditions. Copyright 2009 Elsevier Ltd. All rights reserved.
|Cristofolini, L., Conti, G., Juszczyk, M., Cremonini, S., Van Sint Jan, S., Viceconti, M., 2010. Structural behaviour and strain distribution of the long bones of the human lower limbs. J Biomech 43(5), 826-35 (2010) View|
Although stiffness and strength of lower limb bones have been investigated in the past, information is not complete. While the femur has been extensively investigated, little information is available about the strain distribution in the tibia, and the fibula has not been tested in vitro. This study aimed at improving the understanding of the biomechanics of lower limb bones by: (i) measuring the stiffness and strain distributions of the different low limb bones; (ii) assessing the effect of viscoelasticity in whole bones within a physiological range of strain-rates; (iii) assessing the difference in the behaviour in relation to opposite directions of bending and torsion. The structural stiffness and strain distribution of paired femurs, tibias and fibulas from two donors were measured. Each region investigated of each bone was instrumented with 8-16 triaxial strain gauges (over 600 grids in total). Each bone was subjected to 6-12 different loading configurations. Tests were replicated at two different loading speeds covering the physiological range of strain-rates. Viscoelasticity did not have any pronounced effect on the structural stiffness and strain distribution, in the physiological range of loading rates explored in this study. The stiffness and strain distribution varied greatly between bone segments, but also between directions of loading. Different stiffness and strain distributions were observed when opposite directions of torque or opposite directions of bending (in the same plane) were applied. To our knowledge, this study represents the most extensive collection of whole-bone biomechanical properties of lower limb bones. Copyright (c) 2009 Elsevier Ltd. All rights reserved.