Cortical thinning and accumulation of large cortical pores in the tibia reflect local structural deterioration of the femoral neck

Iori, Gianluca; Schneider, Johannes; Reisinger, Andreas; Heyer, Frans; Peralta, Laura; Wyers, Caroline; Glüer, Claus C.; van den Bergh, J. P.; Pahr, Dieter; Raum, Kay

Affiliations

¹Berlin-Brandenburg Center for Regenerative Therapies, Charité – Universitätsmedizin Berlin, Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany

²Division Biomechanics, Karl Landsteiner University of Health Sciences, Krems, Austria

³Department of Internal Medicine, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University Medical Center, Maastricht, the Netherlands

⁴Department of Internal Medicine, VieCuri Medical Center, Venlo, the Netherlands

⁵Laboratoire d'Imagerie Biomédicale, Sorbonne Universités, INSERM UMR S 1146, CNRS UMR 7371, Paris, France

⁶Department of Biomedical Engineering, School of Biomedical Engineering & Imaging Sciences, King's College London, London, UK

⁷Sektion Biomedizinische Bildgebung, Klinik für Radiologie und Neuroradiologie, Christian-Albrechts-Universität zu Kiel, Kiel, Germany

⁸Institute for Lightweight Design and Structural Biomechanics, TU Wien, Vienna, Austria

Abstract and keywords

Introduction: Cortical bone thinning and a rarefaction of the trabecular architecture represent possible causes of increased femoral neck (FN) fracture risk. Due to X-ray exposure limits, the bone microstructure is rarely measurable in the FN of subjects but can be assessed at the tibia. Here, we studied whether changes of the tibial cortical microstructure, which were previously reported to be associated with femur strength, are also associated with structural deteriorations of the femoral neck.

Methods: The cortical and trabecular architectures in the FN of 19 humans were analyzed ex vivo on 3D microcomputed tomography images with 30.3 μm voxel size. Cortical thickness (Ct.Th_tibia), porosity (Ct.Po_tibia) and pore size distribution in the tibiae of the same subjects were measured using scanning acoustic microscopy (12 μm pixel size). Femur strength during sideways falls was simulated with homogenized voxel finite element models.

Results: Femur strength was associated with the total (vBMDtot; R² = 0.23, p < 0.01) and trabecular (vBMDtrab; R² = 0.26, p < 0.01) volumetric bone mineral density (vBMD), with the cortical thickness (Ct.Th_FN; R² = 0.29, p < 0.001) and with the trabecular bone volume fraction (Tb.BV/TV_FN; R² = 0.34, p < 0.001), separation (Tb.Sp_FN; R² = 0.25, p < 0.01) and number (Tb.NFN; R² = 0.32, p < 0.001) of the femoral neck. Moreover, smaller Ct.Th_tibia was associated with smaller Ct.Th_FN (R² = 0.31, p < 0.05), lower Tb.BV/TV_FN (R² = 0.29, p < 0.05), higher Tb.Sp_FN (R² = 0.33, p < 0.05) and lower Tb.NFN (R² = 0.42, p < 0.01). A higher prevalence of pores with diameter > 100 μm in tibial cortical bone (relCt.Po100_μm-tibia) indicated higher Tb.Sp_FN (R² = 0.36, p < 0.01) and lower Tb.NFN (R² = 0.45, p < 0.01).

Conclusion: Bone resorption and structural decline of the femoral neck may be identified in vivo by measuring cortical bone thickness and large pores in the tibia.

Keywords: Cortical bone; Porosity; Bone strength; Finite element analysis; Hip fragility

Links

DOI: 10.1016/j.bone.2020.115446

PubMed: 32450342

WoS: 000547005800049

History

Received: 2020-01-26

Revised: 2020-05-19

Accepted: 2020-05-19

Online: 2020-05-22

Cited Works (29)

Year	Entry
2010	Chen H, Zhou X, Shoumura S, Emura S, Bunai Y. Age- and gender-dependent changes in three-dimensional microstructure of cortical and trabecular bone at the human femoral neck. Osteoporos Int. April 2010;21(4):627-636.
2015	Manske SL, Zhu Y, Sandino C, Boyd SK. Human trabecular bone microarchitecture can be assessed independently of density with second generation HR-pQCT. Bone. October 2015;79:213-221.
2014	Andersen TL, Hauge EM, Rolighed L, Bollerslev J, Kjærsgaard-Andersen P, Delaisse J-M. Correlation between absence of bone remodeling compartment canopies, reversal phase arrest, and deficient bone formation in post-menopausal osteoporosis. Am J Pathol. April 2014;184(4):1142-1151.
2014	Nawathe S, Akhlaghpour H, Bouxsein ML, Keaveny TM. Microstructural failure mechanisms in the human proximal femur for sideways fall loading. J Bone Miner Res. February 2014;29(2):507-515.
2001	Keyak JH, Skinner HB, Fleming JA. Effect of force direction on femoral fracture load for two types of loading conditions. J Orthop Res. July 2001;19(4):539-544.
2009	de Bakker PM, Manske SL, Ebacher V, Oxland TR, Cripton PA, Guy P. During sideways falls proximal femur fractures initiate in the superolateral cortex: evidence from high-speed video of simulated fractures. J Biomech. August 25, 2009;42(12):1917-1925.
2018	Bakalova LP, Andreasen CM, Thomsen JS, Brüel A, Hauge E-M, Kiil BJ, Delaisse J-M, Andersen TL, Kersh ME. Intracortical bone mechanics are related to pore morphology and remodeling in human bone. J Bone Miner Res. December 2018;33(12):2177-2185.
2013	Patsch JM, Burghardt AJ, Yap SP, Baum T, Schwartz AV, Joseph GB, Link TM. Increased cortical porosity in type 2 diabetic postmenopausal women with fragility fractures. J Bone Miner Res. February 2013;28(2):313-324.
2009	Dalzell N, Kaptoge S, Morris N, Berthier A, Koller B, Braak L, van Rietbergen B, Reeve J. Bone micro-architecture and determinants of strength in the radius and tibia: age-related changes in a population-based study of normal adults measured with high-resolution pQCT. Osteoporos Int. October 2009;20(10):1683-1694.
2017	Lassen NE, Andersen TL, Pløen GG, Søe K, Hauge EM, Harving S, Eschen GET, Delaisse J-M. Coupling of bone resorption and formation in real time: new knowledge gained from human Haversian BMUs. J Bone Miner Res. July 2017;32(7):1395-1405.
2020	Iori G, Peralta L, Reisinger A, Heyer F, Wyers C, van den Bergh J, Pahr D, Raum K. Femur strength predictions by nonlinear homogenized voxel finite element models reflect the microarchitecture of the femoral neck. Med Eng Phys. May 2020;79:60-66.
2010	Burghardt AJ, Buie HR, Laib A, Majumdar S, Boyd SK. Reproducibility of direct quantitative measures of cortical bone microarchitecture of the distal radius and tibia by HR-pQCT. Bone. September 2010;47(3):519-528.
2009	Holzer G, von Skrbensky G, Holzer LA, Pichl W. Hip fractures and the contribution of cortical versustrabecular bone to femoral neck strength. J Bone Miner Res. March 2009;24(3):468-474.
2010	Nishiyama KK, Macdonald HM, Buie HR, Hanley DA, Boyd SK. Postmenopausal women with osteopenia have higher cortical porosity and thinner cortices at the distal radius and tibia than women with normal aBMD: an in vivo HR-pQCT study. J Bone Miner Res. April 2010;25(4):882-890.
1999	Bell KL, Loveridge N, Power J, Garrahan N, Meggitt BF, Reeve J. Regional differences in cortical porosity in the fractured femoral neck. Bone. January 1999;24(1):57-64.
2007	Fratzl P, Weinkamer R. Nature’s hierarchical materials. Prog Mater Sci. November 2007;52(8):1263-1334.
2016	Shanbhogue VV, Brixen K, Hansen S. Age- and sex-related changes in bone microarchitecture and estimated strength: a three-year prospective study using HRpQCT. J Bone Miner Res. August 2016;31(8):1541-1549.
2013	Zebaze R, Ghasem-Zadeh A, Mbala A, Seeman E. A new method of segmentation of compact-appearing, transitional and trabecular compartments and quantification of cortical porosity from high resolution peripheral quantitative computed tomographic images. Bone. May 2013;54(1):8-20.
1997	Hildebrand T, Rüegsegger P. A new method for the model-independent assessment of thickness in three-dimensional images. J Microsc (Oxford). 1997;185(1):67-75.
1978	Ridler TW, Calvard S. Picture thresholding using an iterative selection method. IEEE Trans Sys Man Cyb. 1978;8(8):630-632.
1999	Bell KL, Loveridge N, Power J, Garrahan N, Stanton M, Lunt M, Meggitt BF, Reeve J. Structure of the femoral neck in hip fracture: cortical bone loss in the inferoanterior to superoposterior axis. J Bone Miner Res. January 1999;14(1):111-119.
2008	Verhulp E, van Rietbergen B, Huiskes R. Load distribution in the healthy and osteoporotic human proximal femur during a fall to the side. Bone. January 2008;42(1):30-35.
2003	Van Rietbergen B, Huiskes R, Eckstein F, Rüegsegger P. Trabecular bone tissue strains in the healthy and osteoporotic human femur. J Bone Miner Res. October 2003;18(10):1781-1788.
1997	Lang TF, Keyak JH, Heitz MW, Augat P, Liu Y, Mathur A, Genant HK. Volumetric quantitative computed tomography of the proximal femur: precision and relation to bone strength. Bone. July 1997;21(1):101-108.
2008	Boyd SK. Site-specific variation of bone micro-architecture in the distal radius and tibia. J Clin Densitom. July–September 2008;11(3):424-430.
2002	Seeman E. Pathogenesis of bone fragility in women and men. Lancet. May 25, 2002;359(9320):1841-1850.
2013	Dall'Ara E, Luisier B, Schmidt R, Kainberger F, Zysset P, Pahr D. A nonlinear QCT-based finite element model validation study for the human femur tested in two configurations in vitro. Bone. January 2013;52(1):27-38.
2000	Jordan GR, Loveridge N, Bell KL, Power J, Rushton N, Reeve J. Spatial clustering of remodeling osteons in the femoral neck cortex: a cause of weakness in hip fracture? Bone. March 2000;26(3):305-313.
2015	Zani L, Erani P, Grassi L, Taddei F, Cristofolini L. Strain distribution in the proximal human femur during in vitro simulated sideways fall. J Biomech. July 16, 2015;48(10):2130-2143.