Generation of a subject-specific model requires a lot of manual work and time in segmentation of soft tissues, meshing and making models to converge. In future studies, the methodology presented in this thesis should be coupled with semi-automatic or fully automatic segmentation techniques [197, 260, 261, 338–344]
and automated meshing tools [262]. In a recent automated model generation approach the only required inputs to generate the entire FE model are the anatomical dimensions from MRI or CT [195]. As motion capture systems are not readily available in clinical settings, a simple and fast method should be developed to obtain and implement patient’s gait. For instance, differences between patient-specific and population-specific (e.g. normal/early/advanced OA populations) motions could be studied [293, 345]. If the population-specific approach would produce similar results with the patient-specific method, it could be used without motion capture. These aforementioned methods would ease the applications of the FE models in large cohort studies to identify areas susceptible to OA development [37–39, 197, 239, 321]. In patients with traumatic knee joint injuries, this methodology may help identify optimal surgical or conservative rehabilitation options to delay the OA onset and progression.
9 Summary and Conclusion
In this thesis, a methodology for rapidly identifying areas prone to OA onset and progression using subject-specific computational knee joint modeling is presented.
The areas identified to have an elevated risk of cartilage degeneration were verified against patient follow-up information. The following conclusions can be drawn based on the present findings:
1. Subject-specific FE models with a simplified geometry and motion, including only cartilage menisci and ligaments, can produce similar cartilage responses as more complicated FE models, which include more tissue structures and complicated motion implementation. These models are much faster and easier to implement (Study I).
2. The FE model predictions match MRI follow-up information both qualitatively and quantitatively for both healthy controls and ACL reconstructed patients.
There is a strong relationship between the predicted maximum principal stress and the measured change inT2relaxation time (Studies IIandIII). For rapid assessment of OA risk level, excessive maximum principal stresses may be a good initial indicator for OA onset and progression at the compartment level.
3. Cartilage lesions following ACL injury and reconstruction should be included in FE models, since they may contribute to OA onset and development. Large tissue deformations around cartilage lesions and/or extensive PG leakage through damaged surfaces may lead to a decrease in FCD content (Study IV).
Subject-specific FE models with simplified geometry, motion and materials can rapidly identify patients at risk of developing OA. In addition, the effect of surgical intervention, such as ACL reconstruction, on OA progression, could be estimated.
If coupled with automatic FE model generation methods, this could be applied as a clinical tool to personalize and optimize OA treatment plans. This could delay the need for total knee replacement surgery, decreasing the financial burden on both the patient and society and increase patient quality of life.
BIBLIOGRAPHY
[1] V. C. Mow and R. Huiskes, Basic orthopaedic biomechanics & mechanobiology (Lippincott Williams & Wilkins, 2005).
[2] Arthritis Foundation, “Osteoarthritis,” (2019).
[3] World Health Organisation, “Priority diseases and reasons for inclusion,”
(2019).
[4] World Health Organization, “Chronic rheumatic conditions,” (2016).
[5] UK National Health Service, “Osteoarthritis,” (2019).
[6] M. A. Risberg, B. E. Oiestad, R. Gunderson, A. K. Aune, L. Engebretsen, A. Culvenor, and I. Holm, “Changes in knee osteoarthritis, symptoms, and function after anterior cruciate ligament reconstruction,”The American Journal of Sports Medicine44, 1215–1224 (2016).
[7] B. Barenius, S. Ponzer, A. Shalabi, R. Bujak, L. Norlén, and K. Eriksson,
“Increased risk of osteoarthritis after anterior cruciate ligament reconstruction:
A 14-year follow-up study of a randomized controlled trial,”American Journal of Sports Medicine42, 1049–1057 (2014).
[8] F. Eckstein, W. Wirth, L. S. Lohmander, M. I. Hudelmaier, and R. B. Frobell,
“Five-year follow-up of knee joint cartilage thickness changes after acute rupture of the anterior cruciate ligament,” Arthritis & Rheumatology 67, 152–
161 (2015).
[9] B. E. Øiestad, I. Holm, L. Engebretsen, A. K. Aune, R. Gunderson, and M. A. Risberg, “The prevalence of patellofemoral osteoarthritis 12 years after anterior cruciate ligament reconstruction,” Knee Surgery, Sports Traumatology, Arthroscopy21, 942–949 (2013).
[10] T. Järvelä, T. Paakkala, P. Kannus, and M. Järvinen, “The incidence of patellofemoral osteoarthritis and associated findings 7 years after anterior cruciate ligament reconstruction with a bone-patellar tendon-bone autograft,”
The American Journal of Sports Medicine29, 18–24 (2001).
[11] R. P. A. Janssen, A. W. F. du Mée, J. van Valkenburg, H. A. G. M. Sala, and C. M. Tseng, “Anterior cruciate ligament reconstruction with 4-strand hamstring autograft and accelerated rehabilitation: a 10-year prospective study on clinical results, knee osteoarthritis and its predictors,”Knee Surgery, Sports Traumatology, Arthroscopy21, 1977–1988 (2013).
[12] L. S. Lohmander, A. Östenberg, M. Englund, and H. Roos, “High prevalence of knee osteoarthritis, pain, and functional limitations in female soccer players twelve years after anterior cruciate ligament injury,” Arthritis & Rheumatism 50, 3145–3152 (2004).
[13] A. G. Culvenor, J. L. Cook, N. J. Collins, and K. M. Crossley, “Is patellofemoral joint osteoarthritis an under-recognised outcome of anterior cruciate ligament reconstruction? A narrative literature review,”British Journal of Sports Medicine 47, 66–70 (2013).
[14] A. Williams, C. S. Winalski, and C. R. Chu, “Early articular cartilage MRI T2 changes after anterior cruciate ligament reconstruction correlate with later changes in T2 and cartilage thickness,”Journal of Orthopaedic Research35, 699–
706 (2017).
[15] E. S. Gardinier, K. Manal, T. S. Buchanan, and L. Snyder-Mackler, “Altered loading in the injured knee after ACL rupture,”Journal of Orthopaedic Research 31, 458–464 (2013).
[16] J. M. Konrath, D. J. Saxby, B. A. Killen, C. Pizzolato, C. J. Vertullo, R. S. Barrett, and D. G. Lloyd, “Muscle contributions to medial tibiofemoral compartment contact loading following ACL reconstruction using semitendinosus and gracilis tendon grafts,”Plos ONE12, e0176016 (2017).
[17] E. Wellsandt, E. S. Gardinier, K. Manal, M. J. Axe, T. S. Buchanan, and L. Snyder-Mackler, “Decreased knee joint loading associated with early knee osteoarthritis after anterior cruciate ligament injury,” The American Journal of Sports Medicine44, 143–151 (2016).
[18] J. H. Salmon, A. C. Rat, J. Sellam, M. Michel, J. P. Eschard, F. Guillemin, D. Jolly, and B. Fautrel, “Economic impact of lower-limb osteoarthritis worldwide: a systematic review of cost-of-illness studies,” Osteoarthritis and Cartilage24, 1500–1508 (2016).
[19] P. Kannus, “UKK-instituutti - Liikunta ja nivelrikko,” (2016).
[20] L. B. Murphy, M. G. Cisternas, D. J. Pasta, C. G. Helmick, and E. H. Yelin,
“Medical expenditures and earnings losses among us adults with arthritis in 2013,”Arthritis Care & Research70, 869–876 (2018).
[21] J. H. Kellgren and J. S. Lawrence, “Radiological assessment of Osteoarthrosis,”
Annals of the Rheumatic Diseases16, 494–502 (1957).
[22] C. Peterfy, A. Guermazi, S. Zaim, P. Tirman, Y. Miaux, D. White, M. Kothari, Y. Lu, K. Fye, S. Zhao, and H. Genant, “Whole-Organ Magnetic Resonance Imaging Score (WORMS) of the knee in osteoarthritis,” Osteoarthritis and Cartilage12, 177–190 (2004).
[23] J. Lynch, F. Roemer, M. Nevitt, D. Felson, J. Niu, C. Eaton, and A. Guermazi,
“Comparison of BLOKS and WORMS scoring systems part I. Cross sectional comparison of methods to assess cartilage morphology, meniscal damage and bone marrow lesions on knee MRI: data from the osteoarthritis initiative,”
Osteoarthritis and Cartilage18, 1393–1401 (2010).
[24] F. Eckstein, D. Burstein, and T. M. Link, “Quantitative MRI of cartilage and bone: Degenerative changes in osteoarthritis,”NMR in Biomedicine19, 822–854 (2006).
[25] D. J. Hunter, G. H. Lo, D. Gale, A. J. Grainger, A. Guermazi, and P. G.
Conaghan, “The reliability of a new scoring system for knee osteoarthritis MRI and the validity of bone marrow lesion assessment: BLOKS (Boston–Leeds Osteoarthritis Knee Score),”Annals of the Rheumatic Diseases67, 206–211 (2008).
[26] A. Wang, V. Pedoia, F. Su, E. Abramson, M. Kretzschmar, L. Nardo, T. M. Link, C. E. McCulloch, C. Jin, C. B. Ma, and X. Li, “MR T1ρ and T2 of meniscus after acute anterior cruciate ligament injuries,”Osteoarthritis and Cartilage 24, 631–639 (2016).
[27] R. Stahl, A. Luke, X. Li, J. Carballido-Gamio, C. B. Ma, S. Majumdar, and T. M.
Link, “T1ρ, T2 and focal knee cartilage abnormalities in physically active and sedentary healthy subjects versus early OA patients—a 3.0-Tesla MRI study,”
European Radiology19, 132–143 (2009).
[28] F. Su, V. Pedoia, H.-L. Teng, M. Kretzschmar, B. Lau, C. McCulloch, T. Link, C. Ma, and X. Li, “The association between MR T1ρand T2 of cartilage and patient-reported outcomes after ACL injury and reconstruction,”Osteoarthritis and Cartilage24, 1180–1189 (2016).
[29] Y. Wang, A. E. Wluka, G. Jones, C. Ding, and F. M. Cicuttini, “Use magnetic resonance imaging to assess articular cartilage,”Therapeutic Advances in Musculoskeletal Disease4, 77–97 (2012).
[30] M. Jarraya, D. Hayashi, F. W. Roemer, and A. Guermazi, “MR imaging-based semi-quantitative methods for knee osteoarthritis,” Magnetic Resonance in Medical Sciences15, 153–164 (2016).
[31] E. H. G. Oei, J. van Tiel, W. H. Robinson, and G. E. Gold, “Quantitative radiologic imaging techniques for articular cartilage composition: toward early diagnosis and development of disease-modifying therapeutics for osteoarthritis,”Arthritis Care & Research66, 1129–1141 (2014).
[32] F. Su, J. Hilton, L. Nardo, S. Wu, F. Liang, T. Link, C. Ma, and X. Li, “Cartilage morphology and T1ρ and T2 quantification in ACL-reconstructed knees: a 2-year follow-up,”Osteoarthritis and Cartilage21, 1058–1067 (2013).
[33] E. Danso, J. Honkanen, S. Saarakkala, and R. Korhonen, “Comparison of nonlinear mechanical properties of bovine articular cartilage and meniscus,”
Journal of Biomechanics47, 200–206 (2014).
[34] L. Henao-Murillo, K. Ito, and C. C. van Donkelaar, “Collagen damage location in articular cartilage differs if damage is caused by excessive loading magnitude or rate,”Annals of Biomedical Engineering46, 605–615 (2018).
[35] S. Hosseini, M. Veldink, K. Ito, and C. van Donkelaar, “Is collagen fiber damage the cause of early softening in articular cartilage?,”Osteoarthritis and Cartilage21, 136–143 (2013).
[36] G. E. Kempson, “Relationship between the tensile properties of articular cartilage from the human knee and age.,”Annals of the Rheumatic Diseases41, 508–511 (1982).
[37] B. S. Gardiner, F. G. Woodhouse, T. F. Besier, A. J. Grodzinsky, D. G. Lloyd, L. Zhang, and D. W. Smith, “Predicting knee osteoarthritis,” Annals of Biomedical Engineering44, 222–233 (2016).
[38] M. P. LaValley, G. H. Lo, L. L. Price, J. B. Driban, C. B. Eaton, and T. E. McAlindon, “Development of a clinical prediction algorithm for knee osteoarthritis structural progression in a cohort study: value of adding measurement of subchondral bone density,” Arthritis Research & Therapy 19, 95 (2017).
[39] M. E. Mononen, P. Tanska, H. Isaksson, and R. K. Korhonen, “New algorithm for simulation of proteoglycan loss and collagen degeneration in the knee joint: Data from the osteoarthritis initiative,”Journal of Orthopaedic Research36, 1673–1683 (2018).
[40] R. Mootanah, C. Imhauser, F. Reisse, D. Carpanen, R. Walker, M. Koff, M. Lenhoff, S. Rozbruch, A. Fragomen, Z. Dewan, Y. Kirane, K. Cheah, J. Dowell, and H. Hillstrom, “Development and validation of a computational model of the knee joint for the evaluation of surgical treatments for osteoarthritis,” Computer Methods in Biomechanics and Biomedical Engineering 17, 1502–1517 (2014).
[41] A. J. Sophia Fox, A. Bedi, and S. A. Rodeo, “The basic science of articular cartilage: Structure, composition, and function,” Sports Health 1, 461–468 (2009).
[42] S. D. Masouros, A. M. Bull, and A. A. Amis, “Biomechanics of the knee joint,”
Orthopaedics and Trauma24, 84–91 (2010).
[43] C. Adam, F. Eckstein, S. Milz, and R. Putz, “The distribution of cartilage thickness within the joints of the lower limb of elderly individuals,” (1998).
[44] S. Koo, G. E. Gold, and T. P. Andriacchi, “Considerations in measuring cartilage thickness using MRI: Factors influencing reproducibility and accuracy,”Osteoarthritis and Cartilage13, 782–789 (2005).
[45] D. E. Shepherd and B. B. Seedhom, “Thickness of human articular cartilage in joints of the lower limb,”Annals of the Rheumatic Diseases58, 27–34 (1999).
[46] S. Koo and T. Andriacchi, “A comparison of the influence of global functional loads vs. local contact anatomy on articular cartilage thickness at the knee,”
Journal of Biomechanics40, 2961–2966 (2007).
[47] G. Li, E. P. Sang, L. E. DeFrate, M. E. Schutzer, L. Ji, T. J. Gill, and H. E.
Rubash, “The cartilage thickness distribution in the tibiofemoral joint and its correlation with cartilage-to-cartilage contact,” Clinical Biomechanics 20, 736–
744 (2005).
[48] V. C. Mow, A. Ratcliffe, and A. Robin Poole, “Cartilage and diarthrodial joints as paradigms for hierarchical materials and structures,”Biomaterials13, 67–97 (1992).
[49] A. Maroudas and M. Venn, “Chemical composition and swelling of normal and osteoarthrotic femoral head cartilage. II. Swelling,”Annals of the Rheumatic Diseases36, 399–406 (1977).
[50] H. J. Mankin and A. Z. Thrasher, “Water content and binding in normal and osteoarthritic human cartilage,” Journal of Bone and Joint Surgery - Series A57, 76–80 (1975).
[51] G. W. Rong and Y. C. Wang, “The role of cruciate ligaments in maintaining knee joint stability.,” Clinical Orthopaedics and Related Sesearch &NA;, 65–71 (1987).
[52] A. Maroudas, “Physicochemical properties of cartilage in the light of ion exchange theory,”Biophysical Journal8, 575–595 (1968).
[53] M. F. Venn, “Variation of chemical composition with age in human femoral head cartilage,”Annals of the Rheumatic Diseases37, 168–174 (1978).
[54] Y. Luo, D. Sinkeviciute, Y. He, M. Karsdal, Y. Henrotin, A. Mobasheri, P. Önnerfjord, and A. Bay-Jensen, “The minor collagens in articular cartilage,”
Protein and Cell8, 560–572 (2017).
[55] A. Benninghoff, “Form und Bau der Gelenkknorpel in ihren Beziehungen zur Funktion - Zweiter Teil: Der Aufbau des Gelenkknorpels in seinen Beziehungen zur Funktion,” Zeitschrift für Zellforschung und Mikroskopische Anatomie2, 783–862 (1925).
[56] S. Saarakkala, P. Julkunen, P. Kiviranta, J. Mäkitalo, J. S. Jurvelin, and R. K. Korhonen, “Depth-wise progression of osteoarthritis in human articular cartilage: investigation of composition, structure and biomechanics,”
Osteoarthritis and Cartilage18, 73–81 (2010).
[57] J. Yin, Y. Xia, and M. Lu, “Concentration profiles of collagen and proteoglycan in articular cartilage by Fourier transform infrared imaging and principal component regression,”Spectrochimica Acta - Part A: Molecular and Biomolecular Spectroscopy88, 90–96 (2012).
[58] T. E. Hardingham and A. J. Fosang, “Proteoglycans: Many forms and many functions,”FASEB Journal6, 861–870 (1992).
[59] R. A. Stockwell, “The cell density of human articular and costal cartilage.,”
Journal of Anatomy101, 753–63 (1967).
[60] I. Youn, J. B. Choi, L. Cao, L. A. Setton, and F. Guilak, “Zonal variations in the 3D morphology of the chondron measured in situ using serial confocal sections,”Osteoarthritis.Cartilage.14, 889–897 (2006).
[61] M. Wong, P. Wuethrich, P. Eggli, and E. Hunziker, “Zone-specific cell biosynthetic activity in mature bovine articular cartilage: A new method using confocal microscopic stereology and quantitative autoradiography,”Journal of Orthopaedic Research14, 424–432 (1996).
[62] L. Li, M. Buschmann, and A. Shirazi-Adl, “A fibril reinforced nonhomogeneous poroelastic model for articular cartilage: inhomogeneous response in unconfined compression,” Journal of Biomechanics 33, 1533–1541 (2000).
[63] R. K. Korhonen, M. S. Laasanen, J. Töyräs, R. Lappalainen, H. J. Helminen, and J. S. Jurvelin, “Fibril reinforced poroelastic model predicts specifically mechanical behavior of normal, proteoglycan depleted and collagen degraded articular cartilage,”Journal of Biomechanics36, 1373–1379 (2003).
[64] W. Wilson, J. Huyghe, and C. van Donkelaar, “A composition-based cartilage model for the assessment of compositional changes during cartilage damage and adaptation,”Osteoarthritis and Cartilage14, 554–560 (2006).
[65] J. L. Silverberg, S. Dillavou, L. Bonassar, and I. Cohen, “Anatomic variation of depth-dependent mechanical properties in neonatal bovine articular cartilage,”Journal of Orthopaedic Research31, 686–691 (2013).
[66] J. T. A. Mäkelä, Z. S. Rezaeian, S. Mikkonen, R. Madden, S. K. Han, J. S.
Jurvelin, W. Herzog, and R. K. Korhonen, “Site-dependent changes in structure and function of lapine articular cartilage 4 weeks after anterior cruciate ligament transection,”Osteoarthritis and Cartilage22, 869–878 (2014).
[67] W. Wilson, C. van Donkelaar, B. van Rietbergen, K. Ito, and R. Huiskes,
“Stresses in the local collagen network of articular cartilage: a poroviscoelastic fibril-reinforced finite element study,” Journal of Biomechanics 37, 357–366 (2004).
[68] T. M. Quinn, P. Dierickx, and A. J. Grodzinsky, “Glycosaminoglycan network geometry may contribute to anisotropic hydraulic permeability in cartilage under compression.,”Journal of biomechanics34, 1483–90 (2001).
[69] S. Federico and W. Herzog, “On the anisotropy and inhomogeneity of permeability in articular cartilage,” Biomechanics and Modeling in Mechanobiology7, 367–378 (2008).
[70] M. A. Soltz and G. A. Ateshian, “Experimental verification and theoretical prediction of cartilage interstitial fluid pressurization at an impermeable contact interface in confined compression,”Journal of Biomechanics31, 927–934 (1998).
[71] M. A. Soltz and G. A. Ateshian, “Interstitial fluid pressurization during confined compression cyclical loading of articular cartilage,” Annals of Biomedical Engineering28, 150–159 (2000).
[72] V. C. Mow, S. C. Kuei, W. M. Lai, and C. G. Armstrong, “Biphasic creep and stress relaxation of articular cartilage in compression: theory and experiments,”Journal of Biomechanical Engineering102, 73 (1980).
[73] B. Cohen, W. M. Lai, and V. C. Mow, “A transversely isotropic biphasic model for unconfined compression of growth olate and chondroepiphysis,” Journal of Biomechanical Engineering120, 491 (1998).
[74] R. Shirazi, A. Shirazi-Adl, and M. Hurtig, “Role of cartilage collagen fibrils networks in knee joint biomechanics under compression,” Journal of Biomechanics41, 3340–3348 (2008).
[75] R. K. Korhonen and J. S. Jurvelin, “Compressive and tensile properties of articular cartilage in axial loading are modulated differently by osmotic environment,”Medical Engineering and Physics32, 155–160 (2010).
[76] W. C. Bae, V. W. Wong, J. Hwang, J. M. Antonacci, G. E. Nugent-Derfus, M. E. Blewis, M. M. Temple-Wong, and R. L. Sah, “Wear-lines and split-lines of human patellar cartilage: relation to tensile biomechanical properties,”
Osteoarthritis and Cartilage16, 841–845 (2008).
[77] B. M. Nigg, W. Herzog, and W. Herzog, Biomechanics of the musculoskeletal system, Vol. 192, (Wiley, 1999).
[78] E. A. Makris, P. Hadidi, and K. A. Athanasiou, “The knee meniscus:
Structure-function, pathophysiology, current repair techniques, and prospects for regeneration,”Biomaterials32, 7411–7431 (2011).
[79] K. Messner and J. Gao, “The menisci of the knee joint. Anatomical and functional characteristics, and a rationale for clinical treatment,” Journal of Anatomy193, 161–178 (1998).
[80] I. McDermott, “Meniscal tears, repairs and replacement: Their relevance to osteoarthritis of the knee,”British Journal of Sports Medicine45, 292–297 (2011).
[81] P. G. Bullough, L. Munuera, J. Murphy, and A. M. Weinstein, “The strength of the menisci of the knee as it relates to their fine structure.,”Journal of Bone and Joint Surgery - Series B52, 564–567 (1970).
[82] P. G. Scott, T. Nakano, and C. M. Dodd, “Isolation and characterization of small proteoglycans from different zones of the porcine knee meniscus.,”
Biochimica et Biophysica Acta1336, 254–62 (1997).
[83] J. C. Gray, “Neural and vascular anatomy of the menisci of the human knee,”
Journal of Orthopaedic and Sports Physical Therapy29, 23–30 (1999).
[84] S. P. Arnoczky and R. F. Warren, “Microvasculature of the human meniscus,”
The American Journal of Sports Medicine10, 90–95 (1982).
[85] C. D. Harner, J. W. Xerogeanes, G. A. Livesay, G. J. Carlin, B. A. Smith, T. Kusayama, S. Kashiwaguchi, and S. L. Woo, “The human posterior cruciate ligament complex: An interdisciplinary study,”The American Journal of Sports Medicine23, 736–745 (1995).
[86] Y.-B. Song, K. Watanabe, E. Hogan, A. V. D’Antoni, A. C. Dilandro, N. Apaydin, M. Loukas, M. M. Shoja, and R. S. Tubbs, “The fibular collateral ligament of the knee,”Clinical Anatomy27, 789–797 (2014).
[87] R. F. Loeser, “Aging processes and the development of osteoarthritis,”Current Opinion in Rheumatology25, 108–113 (2013).
[88] R. F. Loeser, “Aging and osteoarthritis,” Current Opinion in Rheumatology23, 492–496 (2011).
[89] D. Prieto-Alhambra, A. Judge, M. K. Javaid, C. Cooper, A. Diez-Perez, and N. K. Arden, “Incidence and risk factors for clinically diagnosed knee, hip and hand osteoarthritis: Influences of age, gender and osteoarthritis affecting other joints,”Annals of the Rheumatic Diseases73, 1659–1664 (2014).
[90] H. J. Cho, C. B. Chang, J. H. Yoo, S. J. Kim, and T. K. Kim, “Gender differences in the correlation between symptom and radiographic severity in patients with knee osteoarthritis,” Clinical Orthopaedics and Related Research468, 1749–1758 (2010).
[91] P. Manninen, H. Riihimäki, M. Heliövaara, and P. Mäkelä, “Overweight, gender and knee osteoarthritis.,” International journal of obesity and related metabolic disorders : journal of the International Association for the Study of Obesity 20, 595–7 (1996).
[92] M. E. Zabala, J. Favre, S. F. Scanlan, J. Donahue, and T. P. Andriacchi, “Three-dimensional knee moments of ACL reconstructed and control subjects during gait, stair ascent, and stair descent,”Journal of Biomechanics46, 515–520 (2013).
[93] K. A. McKean, S. C. Landry, C. L. Hubley-Kozey, M. J. Dunbar, W. D. Stanish, and K. J. Deluzio, “Gender differences exist in osteoarthritic gait,” Clinical Biomechanics22, 400–409 (2007).
[94] J. T. Blackburn, B. Pietrosimone, M. S. Harkey, B. A. Luc, and D. N.
Pamukoff, “Inter-limb differences in impulsive loading following anterior cruciate ligament reconstruction in females,” Journal of Biomechanics49, 3017–
3021 (2016).
[95] H. W. Wevers, D. W. Siu, and T. D. Cooke, “A quantitative method of assessing malalignment and joint space loss of the human knee,” Journal of Biomedical Engineering4, 319–324 (1982).
[96] J. R. Moreland, L. W. Bassett, and G. J. Hanker, “Radiographic analysis of the axial alignment of the lower extremity,” Journal of Bone and Joint Surgery -Series A69, 745–749 (1987).
[97] F. A. Khan, M. F. Koff, N. O. Noiseux, K. A. Bernhardt, M. M. O’Byrne, D. R. Larson, K. K. Amrami, and K. R. Kaufman, “Effect of local alignment on compartmental patterns of knee osteoarthritis,” Journal of Bone and Joint Surgery - Series A90, 1961–1969 (2008).
[98] G. M. Brouwer, A. W. V. Tol, A. P. Bergink, J. N. Belo, R. M. D. Bernsen, M. Reijman, H. A. P. Pols, and S. M. A. Bierma-Zeinstra, “Association between valgus and varus alignment and the development and progression of radiographic osteoarthritis of the knee,” Arthritis & Rheumatism 56, 1204–
1211 (2007).
[99] D. Cooke, A. Scudamore, J. Li, U. Wyss, T. Bryan, and P. Costigan, “Axial lower-limb alignment: Comparison of knee geometry in normal volunteers and osteoarthritis patients,”Osteoarthritis and Cartilage5, 39–47 (1997).
[100] D. J. Hunter, J. Niu, D. T. Felson, W. F. Harvey, K. D. Gross, P. McCree, P. Aliabadi, B. Sack, and Y. Zhang, “Knee alignment does not predict incident osteoarthritis: The Framingham osteoarthritis study,”Arthritis & Rheumatism 56, 1212–1218 (2007).
[101] D. J. Hunter, L. Sharma, and T. Skaife, “Alignment and osteoarthritis of the knee,”The Journal of Bone and Joint Surgery: American Volume91, 85–89 (2009).
[102] M. B. Coventry, “Proximal tibial varus osteotomy for osteoarthritis of the lateral compartment of the knee,”Journal of Bone and Joint Surgery - Series A69, 32–38 (1987).
[103] D. B. Kettelkamp, D. R. Wenger, E. Y. Chao, and C. Thompson, “Results of proximal tibial osteotomy. The effects of tibiofemoral angle, stance phase flexion extension, and medial plateau force,”Journal of Bone and Joint Surgery -Series A58, 952–960 (1976).
[104] T. Benzakour, A. Hefti, M. Lemseffer, J. D. El Ahmadi, H. Bouyarmane, and A. Benzakour, “High tibial osteotomy for medial osteoarthritis of the knee: 15 years follow-up,”International Orthopaedics34, 209–215 (2010).
[105] S. Floerkemeier, A. E. Staubli, S. Schroeter, S. Goldhahn, and P. Lobenhoffer,
“Outcome after high tibial open-wedge osteotomy: A retrospective evaluation of 533 patients,” Knee Surgery, Sports Traumatology, Arthroscopy 21, 170–180 (2013).
[106] C. C. Prodromos, T. P. Andriacchi, and J. O. Galante, “A relationship between gait and clinical changes following high tibial osteotomy,”Journal of Bone and Joint Surgery - Series A67, 1188–1194 (1985).
[107] E. Wellsandt, A. Khandha, K. Manal, M. J. Axe, T. S. Buchanan, and L. Snyder-Mackler, “Predictors of knee joint loading after anterior cruciate ligament reconstruction,”Journal of Orthopaedic Research35, 651–656 (2017).
[108] M. Grotle, K. B. Hagen, B. Natvig, F. A. Dahl, and T. K. Kvien, “Obesity and osteoarthritis in knee, hip and/or hand: An epidemiological study in the general population with 10 years follow-up,”BMC Musculoskeletal Disorders9 (2008).
[109] D. T. Felson, J. J. Anderson, A. Naimark, A. M. Walker, and R. F. Meenan,
“Obesity and knee osteoarthritis. The Framingham Study,” Annals of Internal Medicine109, 18–24 (1988).
[110] P. W. Lementowski and S. B. Zelicof, “A Review Paper Obesity and Osteoarthritis "...even in nonmechanical sit-uations, obesity and increased adiposity have a prominent role in OA pathogenesis.",” American Journal of Orthopedics37, 148–151 (2008).
[111] S. P. Messier, “Obesity and Osteoarthritis: Disease Genesis and Nonpharmacologic Weight Management,” Rheumatic Disease Clinics of North America34, 713–729 (2008).
[112] P. Pottie, N. Presle, B. Terlain, P. Netter, D. Mainard, and F. Berenbaum,
“Obesity and osteoarthritis: More complex than predicted!,” Annals of the Rheumatic Diseases65, 1403–1405 (2006).
[113] D. T. Felson, Y. Zhang, J. M. Anthony, A. Naimark, and J. J. Anderson, “Weight loss reduces the risk for symptomatic knee osteoarthritis in women: The framingham study,”Annals of Internal Medicine116, 535–539 (1992).
[114] J. Kay, D. de SA, J. Karlsson, V. Musahl, and O. R. Ayeni, “Anterior cruciate ligament rupture,” Orthopaedic Journal of Sports Medicine 3, 232596711561678 (2015).
[115] M. Krause, K. H. Frosch, F. Freudenthaler, A. Achtnich, W. Petersen, and R. Akoto, “Operative versus conservative treatment of anterior cruciate ligament rupture a systematic review of functional improvement in adults,”
Deutsches Arzteblatt International115, 855–862 (2018).
[116] F. Sailhan and P. Ribinik, “Conservative versus operative treatment for anterior cruciate ligament tear: Results and risk factors for osteoarthritis,” Annals of Physical and Rehabilitation Medicine58, e63–e64 (2015).
[116] F. Sailhan and P. Ribinik, “Conservative versus operative treatment for anterior cruciate ligament tear: Results and risk factors for osteoarthritis,” Annals of Physical and Rehabilitation Medicine58, e63–e64 (2015).