{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,11]],"date-time":"2026-11-11T23:58:47Z","timestamp":1794441527872,"version":"4.9.1"},"reference-count":41,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2020,3,4]],"date-time":"2020-03-04T00:00:00Z","timestamp":1583280000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2020,3,4]],"date-time":"2020-03-04T00:00:00Z","timestamp":1583280000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>At advanced knee osteoarthritis (OA) stages subchondral trabecular bone (STB) is altered. Lower limb alignment plays a role in OA progression and modify the macroscopic loading of the medial and lateral condyles of the tibial plateau. How the properties of the STB relate to alignment and OA stage is not well defined. OA stage (KL scores 2\u20134) and alignment (HKA from 17\u00b0 Varus to 8\u00b0 Valgus) of 30 patients were measured and their tibial plateau were collected after total knee arthroplasty. STB tissue elastic modulus, bone volume fraction (BV\/TV) and trabecula thickness (Tb.Th) were evaluated with nanoindentation and \u00b5CT scans (8.1\u2009\u00b5m voxel-size) of medial and lateral samples of each plateau. HKA and KL scores were statistically significantly associated with STB elastic modulus, BV\/TV and Tb.Th. Medial to lateral BV\/TV ratio correlated with HKA angle (R\u2009=\u2009\u22120.53, p\u2009=\u20090.016), revealing a higher ratio for varus than valgus subjects. STB properties showed lower values for KL stage 4 patients. Tissue elastic modulus ratios and BV.TV ratios were strongly correlated (R\u2009=\u20090.81, p\u2009&lt;\u20090.001). Results showed that both micromechanical and microarchitectural properties of STB are affected by macroscopic loading at late stage knee OA. For the first time, a strong association between tissue stiffness and quantity of OA STB was demonstrated.<\/jats:p>","DOI":"10.1038\/s41598-020-60464-x","type":"journal-article","created":{"date-parts":[[2020,3,4]],"date-time":"2020-03-04T11:02:30Z","timestamp":1583319750000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Tibial subchondral trabecular bone micromechanical and microarchitectural properties are affected by alignment and osteoarthritis stage"],"prefix":"10.1038","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8569-6075","authenticated-orcid":false,"given":"Jean-Baptiste","family":"Renault","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4595-2980","authenticated-orcid":false,"given":"Maximiliano","family":"Carmona","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3047-961X","authenticated-orcid":false,"given":"Chris","family":"Tzioupis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthieu","family":"Ollivier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean-No\u00ebl","family":"Argenson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S\u00e9bastien","family":"Parratte","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick","family":"Chabrand","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,3,4]]},"reference":[{"key":"60464_CR1","doi-asserted-by":"publisher","first-page":"188","DOI":"10.1001\/jama.286.2.188","volume":"286","author":"L Sharma","year":"2001","unstructured":"Sharma, L. et al. The Role of Knee Alignment in Disease Progression and Functional Decline in Knee Osteoarthritis. Jama 286, 188 (2001).","journal-title":"Jama"},{"key":"60464_CR2","doi-asserted-by":"publisher","first-page":"1204","DOI":"10.1002\/art.22515","volume":"56","author":"GM Brouwer","year":"2007","unstructured":"Brouwer, G. M. et al. Association between valgus and varus alignment and the development and progression of radiographic osteoarthritis of the knee. Arthritis Rheum. 56, 1204\u20131211 (2007).","journal-title":"Arthritis Rheum."},{"key":"60464_CR3","doi-asserted-by":"publisher","first-page":"617","DOI":"10.1136\/ard.61.7.617","volume":"61","author":"T Miyazaki","year":"2002","unstructured":"Miyazaki, T., Wada, M. & Kawahara, H. Dynamic load at baseline can predict radiographic disease progression in medial compartment knee osteoarthritis. Ann. Rheum. Dis. 61, 617\u2013622 (2002).","journal-title":"Ann. Rheum. Dis."},{"key":"60464_CR4","doi-asserted-by":"publisher","first-page":"499","DOI":"10.1093\/rheumatology\/40.5.499","volume":"40","author":"M Wada","year":"2001","unstructured":"Wada, M. et al. Relationships among bone mineral densities, static alignment and dynamic load in patients with medial compartment knee osteoarthritis. Rheumatology 40, 499\u2013505 (2001).","journal-title":"Rheumatology"},{"key":"60464_CR5","doi-asserted-by":"publisher","first-page":"101","DOI":"10.1016\/S0736-0266(01)00081-X","volume":"20","author":"DE Hurwitz","year":"2002","unstructured":"Hurwitz, D. E., Ryals, A. R., Karar, A., Case, J. P. & Andriacchi, T. P. Static Alignment is a Better Indicator of the Dynamic Knee Joint Loads During Gait in Subjects with Knee Osteoarthritis Than Radiographic Disease Severity, Toe Out Angle and Pain. Orthop. Res. Soc. 20, 101\u2013107 (2002).","journal-title":"Orthop. Res. Soc."},{"key":"60464_CR6","doi-asserted-by":"publisher","first-page":"1047","DOI":"10.1016\/j.otsr.2017.07.010","volume":"103","author":"C Rivi\u00e8re","year":"2017","unstructured":"Rivi\u00e8re, C. et al. Alignment options for total knee arthroplasty: A systematic review. Orthop. Traumatol. Surg. Res. 103, 1047\u20131056 (2017).","journal-title":"Orthop. Traumatol. Surg. Res."},{"issue":"11","key":"60464_CR7","doi-asserted-by":"publisher","first-page":"665","DOI":"10.1038\/nrrheum.2012.130","volume":"8","author":"David B. Burr","year":"2012","unstructured":"Burr, D. B. & Gallant, M. A. Bone remodelling in osteoarthritis. Nature Reviews Rheumatology, https:\/\/doi.org\/10.1038\/nrrheum.2012.130 (2012).","journal-title":"Nature Reviews Rheumatology"},{"key":"60464_CR8","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/ar2601","volume":"11","author":"DJ Hunter","year":"2009","unstructured":"Hunter, D. J. et al. Bone marrow lesions from osteoarthritis knees are characterized by sclerotic bone that is less well mineralized. Arthritis Res. Ther. 11, 1\u20139 (2009).","journal-title":"Arthritis Res. Ther."},{"key":"60464_CR9","doi-asserted-by":"publisher","first-page":"94","DOI":"10.1016\/j.joca.2012.09.008","volume":"21","author":"GJ Kazakia","year":"2013","unstructured":"Kazakia, G. J. et al. Bone and cartilage demonstrate changes localized to bone marrow edema-like lesions within osteoarthritic knees. Osteoarthr. Cartil. 21, 94\u2013101 (2013).","journal-title":"Osteoarthr. Cartil."},{"key":"60464_CR10","doi-asserted-by":"publisher","first-page":"2413","DOI":"10.1093\/rheumatology\/keq286","volume":"49","author":"SK Tanamas","year":"2010","unstructured":"Tanamas, S. K. et al. Bone marrow lesions in people with knee osteoarthritis predict progression of disease and joint replacement: A longitudinal study. Rheumatology 49, 2413\u20132419 (2010).","journal-title":"Rheumatology"},{"key":"60464_CR11","doi-asserted-by":"publisher","first-page":"855","DOI":"10.1148\/radiol.10091467","volume":"256","author":"MD Crema","year":"2010","unstructured":"Crema, M. D. et al. Subchondral Cystlike Lesions Develop Longitudinally in Areas of Bone Marrow Edema\u2013like Lesions in Patients with or at Risk for Knee Osteoarthritis: Detection with MR Imaging\u2014The MOST Study. Radiology 256, 855\u2013862 (2010).","journal-title":"Radiology"},{"key":"60464_CR12","doi-asserted-by":"publisher","first-page":"1927","DOI":"10.1002\/jor.23474","volume":"35","author":"BC Roberts","year":"2017","unstructured":"Roberts, B. C. et al. Systematic mapping of the subchondral bone 3D microarchitecture in the human tibial plateau: Variations with joint alignment. J. Orthop. Res. 35, 1927\u20131941 (2017).","journal-title":"J. Orthop. Res."},{"key":"60464_CR13","doi-asserted-by":"publisher","first-page":"785","DOI":"10.1002\/jor.23312","volume":"35","author":"MAJ Finnil\u00e4","year":"2017","unstructured":"Finnil\u00e4, M. A. J. et al. Association between subchondral bone structure and osteoarthritis histopathological grade. J. Orthop. Res. 35, 785\u2013792 (2017).","journal-title":"J. Orthop. Res."},{"key":"60464_CR14","doi-asserted-by":"publisher","first-page":"1152","DOI":"10.1016\/j.bone.2012.01.024","volume":"50","author":"LGE Cox","year":"2012","unstructured":"Cox, L. G. E., van Donkelaar, C. C., van Rietbergen, B., Emans, P. J. & Ito, K. Decreased bone tissue mineralization can partly explain subchondral sclerosis observed in osteoarthritis. Bone 50, 1152\u20131161 (2012).","journal-title":"Bone"},{"key":"60464_CR15","doi-asserted-by":"publisher","first-page":"6","DOI":"10.1016\/S0736-0266(02)00093-1","volume":"21","author":"V Patel","year":"2003","unstructured":"Patel, V. et al. MicroCT evaluation of normal and osteoarthritic bone structure in human knee specimens. J. Orthropedic Res. 21, 6\u201313 (2003).","journal-title":"J. Orthropedic Res."},{"key":"60464_CR16","doi-asserted-by":"publisher","first-page":"906","DOI":"10.1302\/0301-620X.85B6.12595","volume":"85-B","author":"M Ding","year":"2003","unstructured":"Ding, M., Odgaard, A. & Hvid, I. Changes in the three-dimensional microstructure of human tibial cancellous bone in early osteoarthritis. J. Bone Joint Surg. Br. 85-B, 906\u2013912 (2003).","journal-title":"J. Bone Joint Surg. Br."},{"key":"60464_CR17","doi-asserted-by":"publisher","first-page":"547","DOI":"10.1016\/j.joca.2018.01.014","volume":"26","author":"BC Roberts","year":"2018","unstructured":"Roberts, B. C. et al. Relationships between in vivo dynamic knee joint loading, static alignment and tibial subchondral bone microarchitecture in end-stage knee osteoarthritis. Osteoarthr. Cartil. 26, 547\u2013556 (2018).","journal-title":"Osteoarthr. Cartil."},{"key":"60464_CR18","doi-asserted-by":"publisher","first-page":"203","DOI":"10.1016\/0883-5403(94)90070-1","volume":"9","author":"PI Zysset","year":"1994","unstructured":"Zysset, P. I., Sonny, M. & Hayes, W. C. Morphology-mechanical Property Relations in Trabecular Bone of the Osteoarthritic proximal Tibia. J. Arthroplasty 9, 203\u2013216 (1994).","journal-title":"J. Arthroplasty"},{"key":"60464_CR19","doi-asserted-by":"publisher","first-page":"641","DOI":"10.1359\/jbmr.1997.12.4.641","volume":"12","author":"B Li","year":"1997","unstructured":"Li, B. & Aspden, R. M. Composition and mechanical properties of cancellous bone from the femoral head of patients with osteoporosis or osteoarthritis. J. Bone Miner. Res. 12, 641\u201351 (1997).","journal-title":"J. Bone Miner. Res."},{"key":"60464_CR20","doi-asserted-by":"publisher","first-page":"914","DOI":"10.1016\/S0736-0266(01)00012-2","volume":"19","author":"JS Day","year":"2001","unstructured":"Day, J. S. et al. A decreased subchondral trabecular bone tissue elastic modulus is associated with pre-arthritic cartilage damage. J. Orthop. Res. 19, 914\u2013918 (2001).","journal-title":"J. Orthop. Res."},{"key":"60464_CR21","doi-asserted-by":"publisher","first-page":"181","DOI":"10.1080\/000164701317323444","volume":"72","author":"M Ding","year":"2001","unstructured":"Ding, M., Danielsen, C. C. & Hvid, I. Bone density does not reflect mechanical properties in early-stage arthrosis. Acta Orthop. Scand. 72, 181\u2013185 (2001).","journal-title":"Acta Orthop. Scand."},{"key":"60464_CR22","doi-asserted-by":"publisher","first-page":"1596","DOI":"10.1172\/JCI867","volume":"101","author":"JP Mansell","year":"1998","unstructured":"Mansell, J. P. & Bailey, A. J. Abnormal cancellous bone collagen metabolism in osteoarthritis. J. Clin. Invest. 101, 1596\u20131603 (1998).","journal-title":"J. Clin. Invest."},{"key":"60464_CR23","first-page":"349","volume":"41","author":"AJ Bailey","year":"2004","unstructured":"Bailey, A. J., Mansell, J. P., Sims, T. J. & Banse, X. Biochemical and mechanical properties of subchondral bone in osteoarthritis. Biorheology 41, 349\u2013358 (2004).","journal-title":"Biorheology"},{"key":"60464_CR24","doi-asserted-by":"publisher","first-page":"1593","DOI":"10.1016\/j.jbiomech.2010.12.022","volume":"44","author":"E Dall\u2019Ara","year":"2011","unstructured":"Dall\u2019Ara, E., \u00d6hman, C., Baleani, M. & Viceconti, M. Reduced tissue hardness of trabecular bone is associated with severe osteoarthritis. J. Biomech. 44, 1593\u20131598 (2011).","journal-title":"J. Biomech."},{"key":"60464_CR25","doi-asserted-by":"publisher","first-page":"66","DOI":"10.1007\/s00223-002-2080-8","volume":"73","author":"AM Coats","year":"2003","unstructured":"Coats, A. M., Zioupos, P. & Aspden, R. M. Material properties of subchondral bone from patients with osteoporosis or osteoarthritis by microindentation testing and electron probe microanalysis. Calcif. Tissue Int. 73, 66\u201371 (2003).","journal-title":"Calcif. Tissue Int."},{"key":"60464_CR26","doi-asserted-by":"publisher","first-page":"1191","DOI":"10.1016\/0021-9290(96)00020-6","volume":"29","author":"MB Gustafson","year":"1996","unstructured":"Gustafson, M. B. et al. Calcium buffering is required to maintain bone stiffness in saline solution. J. Biomech. 29, 1191\u20131194 (1996).","journal-title":"J. Biomech."},{"key":"60464_CR27","doi-asserted-by":"publisher","first-page":"1102","DOI":"10.1016\/j.arth.2015.11.002","volume":"31","author":"GF Tawy","year":"2016","unstructured":"Tawy, G. F., Rowe, P. J. & Riches, P. E. Thermal Damage Done to Bone by Burring and Sawing With and Without Irrigation in Knee Arthroplasty. J. Arthroplasty 31, 1102\u20131108 (2016).","journal-title":"J. Arthroplasty"},{"key":"60464_CR28","doi-asserted-by":"publisher","first-page":"1564","DOI":"10.1557\/JMR.1992.1564","volume":"7","author":"C Oliver","year":"1992","unstructured":"Oliver, C. & Pharr, M. An improved technique for determining hardness and elastic modulus using load and displacement sensing indentation experiments. Journal of Materials Research 7, 1564\u20131583 (1992).","journal-title":"Journal of Materials Research"},{"key":"60464_CR29","doi-asserted-by":"publisher","first-page":"90","DOI":"10.1016\/j.jmbbm.2012.11.005","volume":"18","author":"N Rodriguez-Florez","year":"2013","unstructured":"Rodriguez-Florez, N., Oyen, M. L. & Shefelbine, S. J. Insight into differences in nanoindentation properties of bone. J. Mech. Behav. Biomed. Mater. 18, 90\u201399 (2013).","journal-title":"J. Mech. Behav. Biomed. Mater."},{"key":"60464_CR30","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-018-24258-6","volume":"8","author":"AE Peters","year":"2018","unstructured":"Peters, A. E., Akhtar, R., Comerford, E. J. & Bates, K. T. The effect of ageing and osteoarthritis on the mechanical properties of cartilage and bone in the human knee joint. Sci. Rep. 8, 5931 (2018).","journal-title":"Sci. Rep."},{"key":"60464_CR31","doi-asserted-by":"publisher","first-page":"241","DOI":"10.1016\/j.jmbbm.2017.05.012","volume":"72","author":"X Cai","year":"2017","unstructured":"Cai, X. et al. Cortical bone elasticity measured by resonant ultrasound spectroscopy is not altered by defatting and synchrotron X-ray imaging. J. Mech. Behav. Biomed. Mater. 72, 241\u2013245 (2017).","journal-title":"J. Mech. Behav. Biomed. Mater."},{"key":"60464_CR32","doi-asserted-by":"publisher","first-page":"1653","DOI":"10.1002\/jor.23459","volume":"35","author":"N Reina","year":"2017","unstructured":"Reina, N. et al. BMI-related microstructural changes in the tibial subchondral trabecular bone of patients with knee osteoarthritis. J. Orthop. Res. 35, 1653\u20131660 (2017).","journal-title":"J. Orthop. Res."},{"key":"60464_CR33","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/s12891-016-1226-1","volume":"17","author":"Q Zuo","year":"2016","unstructured":"Zuo, Q. et al. Characterization of nano-structural and nano-mechanical properties of osteoarthritic subchondral bone. BMC Musculoskelet. Disord. 17, 1\u201313 (2016).","journal-title":"BMC Musculoskelet. Disord."},{"key":"60464_CR34","doi-asserted-by":"publisher","first-page":"348","DOI":"10.1016\/j.bone.2009.09.035","volume":"46","author":"U Wolfram","year":"2010","unstructured":"Wolfram, U., Wilke, H. J. & Zysset, P. K. Rehydration of vertebral trabecular bone: Influences on its anisotropy, its stiffness and the indentation work with a view to age, gender and vertebral level. Bone 46, 348\u2013354 (2010).","journal-title":"Bone"},{"key":"60464_CR35","doi-asserted-by":"publisher","first-page":"86","DOI":"10.1016\/j.jmbbm.2016.07.022","volume":"64","author":"M Tomanik","year":"2016","unstructured":"Tomanik, M., Nikodem, A. & Filipiak, J. Microhardness of human cancellous bone tissue in progressive hip osteoarthritis. J. Mech. Behav. Biomed. Mater. 64, 86\u201393 (2016).","journal-title":"J. Mech. Behav. Biomed. Mater."},{"key":"60464_CR36","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-642-59373-4","volume-title":"Principles of Deformity Correction","author":"Dror Paley","year":"2002","unstructured":"Paley, D. Principles of Deformity Correction., https:\/\/doi.org\/10.1007\/978-3-642-59373-4 (Springer Berlin Heidelberg, 2002)."},{"key":"60464_CR37","doi-asserted-by":"publisher","first-page":"45","DOI":"10.1007\/s11999-011-1936-5","volume":"470","author":"J Bellemans","year":"2011","unstructured":"Bellemans, J., Colyn, W., Vandenneucker, H. & Victor, J. The Chitranjan Ranawat Award: Is Neutral Mechanical Alignment Normal for All Patients?: The Concept of Constitutional Varus. Clin. Orthop. Relat. Res. 470, 45\u201353 (2011).","journal-title":"Clin. Orthop. Relat. Res."},{"key":"60464_CR38","doi-asserted-by":"publisher","first-page":"316","DOI":"10.1002\/jbmr.3313","volume":"33","author":"Y Chen","year":"2018","unstructured":"Chen, Y. et al. Subchondral Trabecular Rod Loss and Plate Thickening in the Development of Osteoarthritis. J. Bone Miner. Res. 33, 316\u2013327 (2018).","journal-title":"J. Bone Miner. Res."},{"key":"60464_CR39","doi-asserted-by":"publisher","first-page":"125","DOI":"10.1007\/s00223-014-9873-4","volume":"95","author":"G Kim","year":"2014","unstructured":"Kim, G., Cole, J. H., Boskey, A. L., Baker, S. P. & Van Der Meulen, M. C. H. Reduced tissue-level stiffness and mineralization in osteoporotic cancellous bone. Calcif. Tissue Int. 95, 125\u2013131 (2014).","journal-title":"Calcif. Tissue Int."},{"key":"60464_CR40","doi-asserted-by":"publisher","first-page":"1731","DOI":"10.1016\/j.jbiomech.2010.02.026","volume":"43","author":"U Wolfram","year":"2010","unstructured":"Wolfram, U., Wilke, H. J. & Zysset, P. K. Valid \u00b5 finite element models of vertebral trabecular bone can be obtained using tissue properties measured with nanoindentation under wet conditions. J. Biomech. 43, 1731\u20131737 (2010).","journal-title":"J. Biomech."},{"key":"60464_CR41","first-page":"1","volume":"3674","author":"BG Pijls","year":"2018","unstructured":"Pijls, B. G., Plevier, J. W. M. & Nelissen, R. G. H. H. RSA migration of total knee replacements. Acta Orthop. 3674, 1\u20139 (2018).","journal-title":"Acta Orthop."}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-020-60464-x.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-020-60464-x","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-020-60464-x.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,6]],"date-time":"2022-12-06T07:49:56Z","timestamp":1670312996000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-020-60464-x"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,3,4]]},"references-count":41,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2020,12]]}},"alternative-id":["60464"],"URL":"https:\/\/doi.org\/10.1038\/s41598-020-60464-x","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,3,4]]},"assertion":[{"value":"25 July 2019","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"4 December 2019","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"4 March 2020","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"3975"}}