High-resolution MRI and micro-FE for the evaluation of changes in bone mechanical properties during longitudinal clinical trials: application to calcaneal bone in postmenopausal women after one year of idoxifene treatment

wbldb

van Rietbergen, B.¹; Majumdar, S.²; Newitt, D.²; MacDonald, B.³

High-resolution MRI and micro-FE for the evaluation of changes in bone mechanical properties during longitudinal clinical trials: application to calcaneal bone in postmenopausal women after one year of idoxifene treatment

Clin Biomech (Bristol, Avon). February 2002;17(2):81-88

©2002 Elsevier Science Ltd. All rights reserved

Affiliations

¹Department of Biomedical Engineering, Eindhoven University of Technology, P.O. Box 513, 5600 MB Eindhoven, Netherlands

²Department of Radiology, MRSC, UCSF, San Francisco, CA, USA

³GlaxoSmithKline Pharmaceuticals, Collegeville, PA, USA
Abstract and keywords

Objective: To investigate whether recently developed in vivo high-resolution magnetic resonance-imaging and micro-finite element techniques can monitor changes in bone mechanical properties during long-term clinical trials aiming at evaluating the efficacy of new drugs for the treatment of osteoporosis.

Design: Comparison of baseline and follow-up mechanical parameters calculated using micro-finite element analysis of the calcaneus for subjects participating in a study investigating the effect of idoxifene.

Background: Contemporary measurements for the evaluation of bone mechanical properties, based on dual-energy X-ray absorptiometry measurements, are not very accurate and require large trial populations.

Methods: A total of 56 postmenopausal subjects received either a placebo, 5 mg or 10 mg per day of idoxifene. Magnetic resonance-images of the calcaneus were made at baseline and after one year. Mechanical parameters of a trabecular volume of interest in the calcaneus were calculated using micro-finite element analysis.

Results: Although there were no significant differences between the mean changes in the treated groups and the placebo group, there were significant changes from baseline within groups after one year of treatment. Significant changes, however, were found only for mechanical parameters and only in the treated groups.

Conclusions: The present study is the first demonstration that longitudinal changes in bone mechanical properties due to trabecular micro-architectural changes may be quantified in long-term clinical studies. Since significant changes in mechanical parameters were obtained for the treated groups whereas no significant change in bone mass was found we conclude that the application of these techniques may increase the clinical significance of these trials.

Relevance: A precise diagnosis of in vivo bone mechanical properties that accounts for (changes in) trabecular bone architecture is of particular importance for longitudinal clinical trials aiming at evaluating the efficacy of new drugs since it can lead to clinically relevant results from shorter follow-up intervals and may enable a reduction of the number of patients involved in the trial.

Keywords: Osteoporosis; Bone mechanical properties; Magnetic resonance imaging; Finite element analysis; Bone treatments
Links

DOI: 10.1016/S0268-0033(01)00110-3

PubMed: 11832257

WoS: 000174193700001
History

Received: 2001-07-27

Accepted: 2001-11-07

Cited Works (14)

Year	Entry
1998	Ladd AJC, Kinney JH, Haupt DL, Goldstein SA. Finite‐element modeling of trabecular bone: comparison with mechanical testing and determination of tissue modulus. J Orthop Res. September 1998;16(5):622-628.
1996	Van Rietbergen B, Weinans H, Huiskes R, Polman BJW. Computational strategies for iterative solutions of large FEM applications employing voxel data. Int J Num Meth Eng. August 30, 1996;39(16):2743-2767.
2001	Pistoia W, van Rietbergen B, Laib A, Rüegsegger P. High-resolution three-dimensional-pqct images can be an adequate basis for in-vivo μfe analysis of bone. J Biomech Eng. October 2001;123(2):176-183.
2000	Niebur GL, Feldstein MJ, Yuen JC, Chen TJ, Keaveny TM. High-resolution finite element models with tissue strength asymmetry accurately predict failure of trabecular bone. J Biomech. December 2000;33(12):1575-1583.
1995	Bouxsein ML, Courtney AC, Hayes WC. Ultrasound and densitometry of the calcaneus correlate with the failure loads of cadaveric femurs. Calcif Tiss Int. February 1995;56(2):99-103.
1999	Ulrich D, van Rietbergen B, Laib A, Rüegsegger P. Load transfer analysis of the distal radius from in-vivo high-resolution CT-imaging. J Biomech. August 1999;32(8):821-828.
1999	Van Rietbergen B, Müller R, Ulrich D, Rüegsegger P, Huiskes R. Tissue stresses and strain in trabeculae of a canine proximal femur can be quantified from computer reconstructions. J Biomech. February 1999;32(2):165-173.
1998	Laib A, Häuselmann HJ, Rüegsegger P. In vivo high resolution 3D-QCT of the human forearm. Technol Health Care. 1998;6(5-6):329-337.
1996	van Rietbergen B, Odgaard A, Kabel J, Huiskes R. Direct mechanics assessment of elastic symmetries and properties of trabecular bone architecture. J Biomech. December 1996;29(12):1653-1657.
1998	Ulrich D, van Rietbergen B, Weinans H, Rüegsegger P. Finite element analysis of trabecular bone structure: a comparison of image-based meshing techniques. J Biomech. December 1998;31(12):1187-1192.
1997	Laib A, Hildebrand T, Häuselmann HJ, Rüegsegger P. Ridge number density: a new parameter for in vivo bone structure analysis. Bone. December 1997;21(6):541-546.
1998	van Rietbergen B, Majumdar S, Pistoia W, Newitt DC, Kothari M, Laib A, Rüegsegger P. Assessment of cancellous bone mechanical properties from micro-FE models based on micro-CT, pQCT and MR images. Technol Health Care. December 1998;6(5-6):413-420.
1994	Hollister SJ, Brennan JM, Kikuchi N. A homogenization sampling procedure for calculating trabecular bone effective stiffness and tissue level stres. J Biomech. 1994;27(4):433-444.
1995	van Rietbergen B, Weinans H, Huiskes R, Odgaard A. A new method to determine trabecular bone elastic properties and loading using micromechanical finite-element models. J Biomech. January 1995;28(1):69-81.

Cited By (22)

Year	Entry
2007	McDonnell P, McHugh PE, O’Mahoney D. Vertebral osteoporosis and trabecular bone quality. Ann Biomed Eng. February 2007;35(2):170-189.
2003	Stölken JS, Kinney JH. On the importance of geometric nonlinearity in finite-element simulations of trabecular bone failure. Bone. October 2003;33(4):494-504.
2005	Shefelbine SJ, Simon U, Claes L, Gold A, Gabet Y, Bab I, Müller R, Augat P. Prediction of fracture callus mechanical properties using micro-CT images and voxel-based finite element analysis. Bone. March 2005;36(3):480-488.
2006	Hernandez CJ, Keaveny TM. A biomechanical perspective on bone quality. Bone. December 2006;39(6):1173-1181.
2004	Bourne BC, van der Meulen MCH. Finite element models predict cancellous apparent modulus when tissue modulus is scaled from specimen CT-attenuation. J Biomech. May 2004;37(5):613-621.
2006	Verhulp E, van Rietbergen B, Huiskes R. Comparison of micro-level and continuum-level voxel models of the proximal femur. J Biomech. 2006;39(16):2951-2957.
2008	Harrison NM, McDonnell PF, O’Mahoney DC, Kennedy OD, O’Brien FJ, McHugh PE. Heterogeneous linear elastic trabecular bone modelling using micro-CT attenuation data and experimentally measured heterogeneous tissue properties. J Biomech. August 7, 2008;41(11):2589-2596.
2009	Eswaran SK, Bevill G, Nagarathnam P, Allen MR, Burr DB, Keaveny TM. Effects of suppression of bone turnover on cortical and trabecular load sharing in the canine vertebral body. J Biomech. March 11, 2009;42(4):517-523.
2010	Cory E, Nazarian A, Entezari V, Vartanians V, Müller R, Snyder BD. Compressive axial mechanical properties of rat bone as functions of bone volume fraction, apparent density and micro-CT based mineral density. J Biomech. March 22, 2010;43(5):953-960.
2011	Nazarian A, Arroyo FJA, Rosso C, Aran S, Snyder BD. Tensile properties of rat femoral bone as functions of bone volume fraction, apparent density and volumetric bone mineral density. J Biomech. September 2, 2011;44(13):2482-2488.
2006	Zauel R, Yeni YN, Bay BK, Dong XN, Fyhrie DP. Comparison of the linear finite element prediction of deformation and strain of human cancellous bone to 3D digital volume correlation measurements. J Biomech Eng. February 2006;128(1):1-6.
2011	Jungmann R, Szabo ME, Schitter G, Tang RY-S, Vashishth D, Hansma PK, Thurner PJ. Local strain and damage mapping in single trabeculae during three-point bending tests. J Mech Behav Biomed Mater. May 2011;4(4):523-534.
2003	Bouxsein ML. Bone quality: where do we go from here? Osteoporos Int. September 2003;14(suppl 5):S118-S127.
2007	Liu XS. High-Resolution Image Based Micro-Mechanical Modeling of Trabecular Bone [PhD thesis]. Columbia University; 2007.
2010	Zhang XH. High Resolution Imaging Based Patient Specific Biomechanical Assessment of Bone Quality [PhD thesis]. New York, NY: Columbia University; 2010.
2015	Zhou B. Bone Quality Assessment Using High Resolution Peripheral Quantitative Computed Tomography (HR-PQCT) [PhD thesis]. Columbia University; 2015.
2008	Nazarian A. Relative Interaction of Material and Structure in Normal and Pathologic Bone [PhD thesis]. Swiss Federal Institute of Technology Zürich; 2008.
2002	Follet H. Caractérisation Biomécanique Et Modélisation 3D Par Imagerie X Et IRM Haute Résolution De L’os Spongieux Humain: Evaluation Du Risque Fracturaire [PhD thesis]. Institut national des sciences appliquées de Lyon (INSA Lyon); 2002.
2016	Chen Y. Verification and Validation of MicroCT-Based Finite Element Models of Bone Tissue Biomechanics [PhD thesis]. Sheffield, UK: University of Sheffield; July 2016.
2004	Mittra ES. Assessment of Trabecular Bone Quality Using Microstructure, Micro-Mechanics and Micro-Finite Element Modeling [PhD thesis]. Stony Brook, NY: Stony Brook University; May 2004.
2006	Verhulp E. Analyses of Trabecular Bone Failure [PhD thesis]. Eindhoven, The Netherlands: Eindhoven University of Technology; 2006.
2010	Wald MJ. Mapping Trabecular Bone Fabric Tensor by in Vivo Magnetic Resonance Imaging [PhD thesis]. Philadelphia, PA: University of Pennsylvania; 2010.