Z Orthop Unfall 2016; 154(03): 254-268
DOI: 10.1055/s-0042-100478
Übersicht
Georg Thieme Verlag KG Stuttgart · New York

Frühdiagnose der Arthrose: klinische Realität und experimentelle Pipeline

Early Diagnosis of Osteoarthritis: Clinical Reality and Promising Experimental Techniques
C. Arnscheidt
1   Unfall- und Wiederherstellungschirurgie, Berufsgenossenschaftliche Unfallklinik Tübingen
,
A. Meder
1   Unfall- und Wiederherstellungschirurgie, Berufsgenossenschaftliche Unfallklinik Tübingen
,
B. Rolauffs
2   Siegfried-Weller-Institut für Unfallmedizinische Forschung, Berufsgenossenschaftliche Unfallklinik Tübingen
› Author Affiliations
Further Information

Publication History

Publication Date:
19 February 2016 (online)

Zusammenfassung

In der Frühphase der Arthrose wird das Ausmaß des strukturellen Schadens noch als gering und als theoretisch reversibel angesehen. Daher sind Entwicklungen zur Frühdiagnose der Arthrose für unser Fachgebiet von großer Bedeutung. Der vorliegende Review richtet sich an den klinisch tätigen Orthopäden und Unfallchirurgen und stellt anhand von 3 Fallbeispielen den gegenwärtigen Stand der klinischen Routineversorgung sowie experimentelle Strategien mit translationalem Charakter dar. Im Einzelnen werden nicht invasive bildgebende Verfahren wie die quantitative Magnetresonanztomografie (MRT), die MRT-Fusionsbildgebung, die Ultraschalltechnik sowie Ultraschallfusionsbildgebungen, die optische Kohärenztomografie (OCT), die Szintigrafie und das sog. Diffraction-Enhanced Synchrotron Imaging (DEI) sowie biochemische Verfahren und die Proteomik berücksichtigt. Anschließend werden minimalinvasive Verfahren wie die Arthroskopie sowie Fusionen der Arthroskopie mit Indentationstechniken, der Spektrometrie und der Multiphotonenmikroskopie und invasive Verfahren wie die Makroskopie und die Histologie in Bezug auf die Frühdiagnose der Arthrose diskutiert. Zuletzt werden Veränderungen in der räumlichen Organisation humaner Chondrozyten als Beispiel eines bildbasierten Biomarkers dargestellt. Dieser beruht nicht auf dem Nachweis struktureller Schäden, sondern berücksichtigt frühe Veränderungen der Gewebearchitektur potenziell vor dem Auftreten erster Schäden und außerhalb von Arthroseläsionen. Zusammenfassend sind viele relativ kliniknahe (translationale) Techniken bereits jetzt in der Lage, frühe strukturelle Schäden experimentell zu erkennen. Allerdings ist das Abschätzen der klinischen Relevanz dieser vielen Techniken aufgrund fehlender Daten noch nicht möglich und eine vergleichende Bewertung der einzelnen Verfahren ist derzeit kaum möglich. Diese vielen relativ kliniknahen Techniken werden unser Verständnis frühester Arthroseprozesse deutlich verbessern, was wiederum als Katalysator für die Entwicklung effektiver Strategien für die Frühdiagnose, Frühtherapie oder gar Prävention wirken kann. Nichtsdestotrotz bleibt die klinische Diagnose der Früharthrose eines der großen Ziele unseres Fachgebiets. Die Verwirklichung dieses Zieles ist am Horizont sichtbar, aber der Weg dorthin wird noch durch viele weiße Flecken auf der Karte führen.

Abstract

It is considered that the structural damage in early osteoarthritis (OA) is potentially reversible. It is therefore particularly important for orthopaedic and trauma surgery to develop strategies and technologies for diagnosing early OA processes. This review presents 3 case reports to illustrate the current clinical diagnostic procedure for OA. Experimental techniques with translational character are discussed in the context of the detection of early degenerative processes relevant to OA. Non-invasive imaging methods such as quantitative MRI, ultrasound, optical coherence tomography (OCT), scintigraphy and diffraction-enhanced synchrotron imaging (DEI), as well as biochemical methods and proteomics, are considered. Early detection of OA is reviewed with minimally invasive techniques, such as arthroscopy, as well as the combination of arthroscopic techniques with indentation, spectrometry, and multiphoton microscopy. In addition, a brief summary of macroscopic and histologic scores is presented. Finally, the spatial organisation of joint surface chondrocytes as an image-based biomarker is used to illustrate an early OA detection strategy that focusses on early changes in tissue architecture potentially prior to damage. In summary, multiple translational techniques are able to detect early OA processes but we do not know whether they truly represent the initial events. Moreover, at this point it is difficult to judge the future clinical relevance of these procedures and to compare their efficacy, as there have been comparative studies. However, the expected gain in knowledge will hopefully help us top attain a more comprehensive understanding of early OA and to develop novel methods for its early diagnosis, therapy, and prevention. Overall, the clinical diagnosis of early OA remains one of the greatest challenges of our field. We still face uncharted territory.

 
  • Literatur

  • 1 Woolf AD, Pfleger B. Burden of major musculoskeletal conditions. Bull World Health Organ 2003; 81: 646-656
  • 2 Mobasheri A. The future of osteoarthritis therapeutics: targeted pharmacological therapy. Curr Rheumatol Rep 2013; 15: 364
  • 3 Felson DT. The epidemiology of knee osteoarthritis: results from the Framingham Osteoarthritis Study. Semin Arthritis Rheum 1990; 20: 42-50
  • 4 Saltzman CL, Zimmerman MB, OʼRourke M et al. Impact of comorbidities on the measurement of health in patients with ankle osteoarthritis. J Bone Joint Surg Am 2006; 88: 2366-2372
  • 5 Bitton R. The economic burden of osteoarthritis. Am J Manag Care 2009; 15: S230-235
  • 6 Chu CR, Williams AA, Coyle CH et al. Early diagnosis to enable early treatment of pre-osteoarthritis. Arthritis Res Ther 2012; 14: 212
  • 7 Chevalier X, Eymard F, Richette P. Biologic agents in osteoarthritis: hopes and disappointments. Nat Rev Rheumatol 2013; 9: 400-410
  • 8 Goldring MB. Update on the biology of the chondrocyte and new approaches to treating cartilage diseases. Best Pract Res Clin Rheumatol 2006; 20: 1003-1025
  • 9 Palmer AJ, Brown CP, McNally EG et al. Non-invasive imaging of cartilage in early osteoarthritis. Bone Joint J 2013; 95-B: 738-746
  • 10 Loeser RF, Goldring SR, Scanzello CR et al. Osteoarthritis: a disease of the joint as an organ. Arthritis Rheum 2012; 64: 1697-1707
  • 11 Zacher J, Carl HD, Swoboda B et al. [Imaging of osteoarthritis of the peripheral joints]. Z Rheumatol 2007; 66: 257-258 260–264, 266
  • 12 Zacher J, Gursche A. [Diagnosis of arthrosis]. Orthopade 2001; 30: 841-847
  • 13 Boegard T, Rudling O, Petersson IF et al. Correlation between radiographically diagnosed osteophytes and magnetic resonance detected cartilage defects in the tibiofemoral joint. Ann Rheum Dis 1998; 57: 401-407
  • 14 Chu Miow Lin D, Reichmann WM, Gossec L et al. Validity and responsiveness of radiographic joint space width metric measurement in hip osteoarthritis: a systematic review. Osteoarthritis Cartilage 2011; 19: 543-549
  • 15 Down C, Xu Y, Osagie LE et al. The lack of correlation between radiographic findings and cartilage integrity. J Arthroplasty 2011; 26: 949-954
  • 16 Kellgren JH, Lawrence JS. Radiological Assessment of Osteo-Arthrosis. Ann Rheum Dis 1957; 16: 494-502
  • 17 Schiphof D, Boers M, Bierma-Zeinstra SM. Differences in descriptions of Kellgren and Lawrence grades of knee osteoarthritis. Ann Rheum Dis 2008; 67: 1034-1036
  • 18 Saltzman CL, Salamon ML, Blanchard GM et al. Epidemiology of ankle arthritis: report of a consecutive series of 639 patients from a tertiary orthopaedic center. Iowa Orthop J 2005; 25: 44-46
  • 19 Stufkens SA, Knupp M, Horisberger M et al. Cartilage lesions and the development of osteoarthritis after internal fixation of ankle fractures: a prospective study. J Bone Joint Surg Am 2010; 92: 279-286
  • 20 Gold GE, Chen CA, Koo S et al. Recent advances in MRI of articular cartilage. AJR Am J Roentgenol 2009; 193: 628-638
  • 21 Smith TO, Drew BT, Toms AP et al. Accuracy of magnetic resonance imaging, magnetic resonance arthrography and computed tomography for the detection of chondral lesions of the knee. Knee Surg Sports Traumatol Arthrosc 2012; 20: 2367-2379
  • 22 Williams A, Sharma L, McKenzie CA et al. Delayed gadolinium-enhanced magnetic resonance imaging of cartilage in knee osteoarthritis: findings at different radiographic stages of disease and relationship to malalignment. Arthritis Rheum 2005; 52: 3528-3535
  • 23 Gatlin CC, Matheny LM, Ho CP et al. Diagnostic accuracy of 3.0 Tesla magnetic resonance imaging for the detection of articular cartilage lesions of the talus. Foot Ankle Int 2015; 36: 288-292
  • 24 Peterfy CG, Guermazi A, Zaim S et al. Whole-Organ Magnetic Resonance Imaging Score (WORMS) of the knee in osteoarthritis. Osteoarthritis Cartilage 2004; 12: 177-190
  • 25 Hani AF, Kumar D, Malik AS et al. Non-invasive and in vivo assessment of osteoarthritic articular cartilage: a review on MRI investigations. Rheumatol Int 2015; 35: 1-16
  • 26 von Engelhardt LV, Lahner M, Klussmann A et al. Arthroscopy vs. MRI for a detailed assessment of cartilage disease in osteoarthritis: diagnostic value of MRI in clinical practice. BMC Musculoskelet Disord 2010; 11: 75
  • 27 Casula V, Hirvasniemi J, Lehenkari P et al. Association between quantitative MRI and ICRS arthroscopic grading of articular cartilage. Knee Surg Sports Traumatol Arthrosc 2014; [Epub ahead of print]
  • 28 Hesper T, Hosalkar HS, Bittersohl D et al. T2* mapping for articular cartilage assessment: principles, current applications, and future prospects. Skeletal Radiol 2014; 43: 1429-1445
  • 29 Shapiro L, Harish M, Hargreaves B et al. Advances in musculoskeletal MRI: technical considerations. J Magn Reson Imaging 2012; 36: 775-787
  • 30 Buckwalter JA, Anderson DD, Brown TD et al. The roles of mechanical stresses in the pathogenesis of osteoarthritis: implications for treatment of joint injuries. Cartilage 2013; 4: 286-294
  • 31 Maly MR. Abnormal and cumulative loading in knee osteoarthritis. Curr Opin Rheumatol 2008; 20: 547-552
  • 32 Kuettner KE, Aydelotte MB, Thonar EJ. Articular cartilage matrix and structure: a minireview. J Rheumatol Suppl 1991; 27: 46-48
  • 33 Lu XL, Mow VC. Biomechanics of articular cartilage and determination of material properties. Med Sci Sports Exerc 2008; 40: 193-199
  • 34 Lu XL, Miller C, Chen FH et al. The generalized triphasic correspondence principle for simultaneous determination of the mechanical properties and proteoglycan content of articular cartilage by indentation. J Biomech 2007; 40: 2434-2441
  • 35 Buschmann MD, Grodzinsky AJ. A molecular model of proteoglycan-associated electrostatic forces in cartilage mechanics. J Biomech Eng 1995; 117: 179-192
  • 36 Lammentausta E, Kiviranta P, Nissi MJ et al. T2 relaxation time and delayed gadolinium-enhanced MRI of cartilage (dGEMRIC) of human patellar cartilage at 1.5 T and 9.4 T: Relationships with tissue mechanical properties. J Orthop Res 2006; 24: 366-374
  • 37 Kretzschmar M, Bieri O, Miska M et al. Characterization of the collagen component of cartilage repair tissue of the talus with quantitative MRI: comparison of T2 relaxation time measurements with a diffusion-weighted double-echo steady-state sequence (dwDESS). Eur Radiol 2015; 25: 980-986
  • 38 Hani AFM, Kumar D, Malik AS et al. Fusion of multinuclear magnetic resonance images of knee for the assessment of articular cartilage. Engineering in Medicine and Biology Society (EMBC). 35th Annual International Conference of the IEEE. 2013: 6466-6469
  • 39 Bittersohl B, Miese FR, Hosalkar HS et al. T2* mapping of hip joint cartilage in various histological grades of degeneration. Osteoarthritis Cartilage 2012; 20: 653-660
  • 40 Williams A, Qian Y, Bear D et al. Assessing degeneration of human articular cartilage with ultra-short echo time (UTE) T2* mapping. Osteoarthritis Cartilage 2010; 18: 539-546
  • 41 Bittersohl B, Hosalkar HS, Miese FR et al. Zonal T2* and T1Gd assessment of knee joint cartilage in various histological grades of cartilage degeneration: an observational in vitro study. BMJ Open 2015; 5: e006895
  • 42 Leumann A, Valderrabano V, Plaass C et al. A novel imaging method for osteochondral lesions of the talus–comparison of SPECT-CT with MRI. Am J Sports Med 2011; 39: 1095-1101
  • 43 Nakamura H, Masuko K, Yudoh K et al. Positron emission tomography with 18 F-FDG in osteoarthritic knee. Osteoarthritis Cartilage 2007; 15: 673-681
  • 44 Iagnocco A, Conaghan PG, Aegerter P et al. The reliability of musculoskeletal ultrasound in the detection of cartilage abnormalities at the metacarpo-phalangeal joints. Osteoarthritis Cartilage 2012; 20: 1142-1146
  • 45 Gutierrez M, Di Geso L, Salaffi F et al. Ultrasound detection of cartilage calcification at knee level in calcium pyrophosphate deposition disease. Arthritis Care Res (Hoboken) 2014; 66: 69-73
  • 46 Iagnocco A, Perricone C, Scirocco C et al. The interobserver reliability of ultrasound in knee osteoarthritis. Rheumatology (Oxford) 2012; 51: 2013-2019
  • 47 Bevers K, Zweers MC, van den Ende CH et al. Ultrasonographic analysis in knee osteoarthritis: evaluation of inter-observer reliability. Clin Exp Rheumatol 2012; 30: 673-678
  • 48 Klauser AS, Faschingbauer R, Kupferthaler K et al. Sonographic criteria for therapy follow-up in the course of ultrasound-guided intra-articular injections of hyaluronic acid in hand osteoarthritis. Eur J Radiol 2012; 81: 1607-1611
  • 49 Wittoek R, Jans L, Lambrecht V et al. Reliability and construct validity of ultrasonography of soft tissue and destructive changes in erosive osteoarthritis of the interphalangeal finger joints: a comparison with MRI. Ann Rheum Dis 2011; 70: 278-283
  • 50 Abraham AM, Goff I, Pearce MS et al. Reliability and validity of ultrasound imaging of features of knee osteoarthritis in the community. BMC Musculoskelet Disord 2011; 12: 70
  • 51 Viren T, Saarakkala S, Kaleva E et al. Minimally invasive ultrasound method for intra-articular diagnostics of cartilage degeneration. Ultrasound Med Biol 2009; 35: 1546-1554
  • 52 Nishitani K, Kobayashi M, Kuroki H et al. Ultrasound can detect macroscopically undetectable changes in osteoarthritis reflecting the superficial histological and biochemical degeneration: ex vivo study of rabbit and human cartilage. PLoS One 2014; 9: e89484
  • 53 Viren T, Huang YP, Saarakkala S et al. Comparison of ultrasound and optical coherence tomography techniques for evaluation of integrity of spontaneously repaired horse cartilage. J Med Eng Technol 2012; 36: 185-192
  • 54 Chu CR, Williams A, Tolliver D et al. Clinical optical coherence tomography of early articular cartilage degeneration in patients with degenerative meniscal tears. Arthritis Rheum 2010; 62: 1412-1420
  • 55 Cernohorsky P, Kok AC, Bruin DM et al. Comparison of optical coherence tomography and histopathology in quantitative assessment of goat talus articular cartilage. Acta Orthop 2015; 86: 257-263
  • 56 te Moller NC, Brommer H, Liukkonen J et al. Arthroscopic optical coherence tomography provides detailed information on articular cartilage lesions in horses. Vet J 2013; 197: 589-595
  • 57 Pilge H, Huber-van der Velden K, Herten M et al. Comparison of hip joint cartilage degeneration assessed by histology and ex vivo optical coherence tomography. Orthop Rev (Pavia) 2014; 6: 5342
  • 58 Rashidifard C, Vercollone C, Martin S et al. The application of optical coherence tomography in musculoskeletal disease. Arthritis 2013; 2013: 563268
  • 59 Samuel AM, Jain H. Scintigraphic changes of osteoarthritis: an analysis of findings during routine bone scans to evaluate the incidence in an Indian population. Indian J Nucl Med 2012; 27: 73-80
  • 60 Addison S, Coleman RE, Feng S et al. Whole-body bone scintigraphy provides a measure of the total-body burden of osteoarthritis for the purpose of systemic biomarker validation. Arthritis Rheum 2009; 60: 3366-3373
  • 61 Vanharanta H, Kuusela T, Kiuru A. Early detection of developing osteoarthritis by scintigraphy: an experimental study on rabbits. Eur J Nucl Med 1984; 9: 426-428
  • 62 Mollenhauer J, Aurich ME, Zhong Z et al. Diffraction-enhanced X-ray imaging of articular cartilage. Osteoarthritis Cartilage 2002; 10: 163-171
  • 63 Muehleman C, Li J, Connor D et al. Diffraction-enhanced imaging of musculoskeletal tissues using a conventional x-ray tube. Acad Radiol 2009; 16: 918-923
  • 64 Rolauffs B, Muehleman C, Li J et al. Vulnerability of the superficial zone of immature articular cartilage to compressive injury. Arthritis Rheum 2010; 62: 3016-3027
  • 65 Rolauffs B, Kurz B, Felka T et al. Stress-vs-time signals allow the prediction of structurally catastrophic events during fracturing of immature cartilage and predetermine the biomechanical, biochemical, and structural impairment. J Struct Biol 2013; 183: 501-511
  • 66 Chapman D, Thomlinson W, Johnston RE et al. Diffraction enhanced x-ray imaging. Phys Med Biol 1997; 42: 2015-2025
  • 67 Li J, Wilson N, Zelazny A et al. Assessment of diffraction-enhanced synchrotron imaging for cartilage degeneration of the human knee joint. Clin Anat 2013; 26: 621-629
  • 68 Li J, Williams JM, Zhong Z et al. Reliability of diffraction enhanced imaging for assessment of cartilage lesions, ex vivo. Osteoarthritis Cartilage 2005; 13: 187-197
  • 69 Lotz M, Martel-Pelletier J, Christiansen C et al. Value of biomarkers in osteoarthritis: current status and perspectives. Ann Rheum Dis 2013; 72: 1756-1763
  • 70 Fuchs S, Rolauffs B, Arndt S et al. CD44 H and the isoforms CD44v5 and CD44v6 in the synovial fluid of the osteoarthritic human knee joint. Osteoarthritis Cartilage 2003; 11: 839-844
  • 71 Ishijima M, Kaneko H, Kaneko K. The evolving role of biomarkers for osteoarthritis. Ther Adv Musculoskelet Dis 2014; 6: 144-153
  • 72 Balakrishnan L, Bhattacharjee M, Ahmad S et al. Differential proteomic analysis of synovial fluid from rheumatoid arthritis and osteoarthritis patients. Clin Proteomics 2014; 11: 1
  • 73 De Seny D, Sharif M, Fillet M et al. Discovery and biochemical characterisation of four novel biomarkers for osteoarthritis. Ann Rheum Dis 2011; 70: 1144-1152
  • 74 Dufield DR, Nemirovskiy OV, Jennings MG et al. An immunoaffinity liquid chromatography-tandem mass spectrometry assay for detection of endogenous aggrecan fragments in biological fluids: Use as a biomarker for aggrecanase activity and cartilage degradation. Anal Biochem 2010; 406: 113-123
  • 75 Fernandez-Puente P, Mateos J, Fernandez-Costa C et al. Identification of a panel of novel serum osteoarthritis biomarkers. J Proteome Res 2011; 10: 5095-5101
  • 76 Gobezie R, Kho A, Krastins B et al. High abundance synovial fluid proteome: distinct profiles in health and osteoarthritis. Arthritis Res Ther 2007; 9: R36
  • 77 Han MY, Dai JJ, Zhang Y et al. Identification of osteoarthritis biomarkers by proteomic analysis of synovial fluid. J Int Med Res 2012; 40: 2243-2250
  • 78 Henrotin Y, Gharbi M, Mazzucchelli G et al. Fibulin 3 peptides Fib3-1 and Fib3-2 are potential biomarkers of osteoarthritis. Arthritis Rheum 2012; 64: 2260-2267
  • 79 Hsueh MF, Onnerfjord P, Kraus VB. Biomarkers and proteomic analysis of osteoarthritis. Matrix Biol 2014; 39: 56-66
  • 80 Mateos J, Lourido L, Fernandez-Puente P et al. Differential protein profiling of synovial fluid from rheumatoid arthritis and osteoarthritis patients using LC-MALDI TOF/TOF. J Proteomics 2012; 75: 2869-2878
  • 81 Nemirovskiy O, Li WW, Szekely-Klepser G. Design and validation of an immunoaffinity LC-MS/MS assay for the quantification of a collagen type II neoepitope peptide in human urine: application as a biomarker of osteoarthritis. Methods Mol Biol 2010; 641: 253-270
  • 82 Nemirovskiy OV, Dufield DR, Sunyer T et al. Discovery and development of a type II collagen neoepitope (TIINE) biomarker for matrix metalloproteinase activity: from in vitro to in vivo. Anal Biochem 2007; 361: 93-101
  • 83 Ritter SY, Subbaiah R, Bebek G et al. Proteomic analysis of synovial fluid from the osteoarthritic knee: comparison with transcriptome analyses of joint tissues. Arthritis Rheum 2013; 65: 981-992
  • 84 Takinami Y, Yoshimatsu S, Uchiumi T et al. Identification of potential prognostic markers for knee osteoarthritis by serum proteomic analysis. Biomark Insights 2013; 8: 85-95
  • 85 Acebes C, Roman-Blas JA, Delgado-Baeza E et al. Correlation between arthroscopic and histopathological grading systems of articular cartilage lesions in knee osteoarthritis. Osteoarthritis Cartilage 2009; 17: 205-212
  • 86 Spahn G, Klinger HM, Baums M et al. Reliability in arthroscopic grading of cartilage lesions: results of a prospective blinded study for evaluation of inter-observer reliability. Arch Orthop Trauma Surg 2011; 131: 377-381
  • 87 Spahn G, Muckley T, Klinger HM et al. Whole-Organ Arthroscopic Knee Score (WOAKS). BMC Musculoskelet Disord 2008; 9: 155
  • 88 Timonen MA, Toyras J, Aula AS et al. Technical and practical improvements in arthroscopic indentation technique for diagnostics of articular cartilage softening. J Med Eng Technol 2011; 35: 40-46
  • 89 Huang YP, Wang SZ, Saarakkala S et al. Quantification of stiffness change in degenerated articular cartilage using optical coherence tomography-based air-jet indentation. Connect Tissue Res 2011; 52: 433-443
  • 90 Kiviranta P, Lammentausta E, Toyras J et al. Indentation diagnostics of cartilage degeneration. Osteoarthritis Cartilage 2008; 16: 796-804
  • 91 Wang Y, Huang YP, Liu A et al. An ultrasound biomicroscopic and water jet ultrasound indentation method for detecting the degenerative changes of articular cartilage in a rabbit model of progressive osteoarthritis. Ultrasound Med Biol 2014; 40: 1296-1306
  • 92 Bae WC, Temple MM, Amiel D et al. Indentation testing of human cartilage: sensitivity to articular surface degeneration. Arthritis Rheum 2003; 48: 3382-3394
  • 93 Changoor A, Coutu JP, Garon M et al. Streaming potential-based arthroscopic device is sensitive to cartilage changes immediately post-impact in an equine cartilage injury model. J Biomech Eng 2011; 133: 061005
  • 94 Kinnunen J, Saarakkala S, Hauta-Kasari M et al. Optical spectral reflectance of human articular cartilage – relationships with tissue structure, composition and mechanical properties. Biomed Opt Express 2011; 2: 1394-1402
  • 95 Afara I, Prasadam I, Crawford R et al. Non-destructive evaluation of articular cartilage defects using near-infrared (NIR) spectroscopy in osteoarthritic rat models and its direct relation to Mankin score. Osteoarthritis Cartilage 2012; 20: 1367-1373
  • 96 Spahn G, Felmet G, Hofmann GO. Traumatic and degenerative cartilage lesions: arthroscopic differentiation using near-infrared spectroscopy (NIRS). Arch Orthop Trauma Surg 2013; 133: 997-1002
  • 97 Spahn G, Plettenberg H, Kahl E et al. Near-infrared (NIR) spectroscopy. A new method for arthroscopic evaluation of low grade degenerated cartilage lesions. Results of a pilot study. BMC Musculoskelet Disord 2007; 8: 47
  • 98 Pester JK, Stumpfe ST, Steinert S et al. [Histological, biochemical and spectroscopic changes of articular cartilage in osteoarthritis: is there a chance for spectroscopic evaluation?]. Z Orthop Unfall 2014; 152: 469-479
  • 99 Spahn G, Plettenberg H, Nagel H et al. Evaluation of cartilage defects with near-infrared spectroscopy (NIR): an ex vivo study. Med Eng Phys 2008; 30: 285-292
  • 100 Hofmann GO, Marticke J, Grossstuck R et al. Detection and evaluation of initial cartilage pathology in man: A comparison between MRT, arthroscopy and near-infrared spectroscopy (NIR) in their relation to initial knee pain. Pathophysiology 2010; 17: 1-8
  • 101 Johansson A, Kuiper JH, Sundqvist T et al. Spectroscopic measurement of cartilage thickness in arthroscopy: ex vivo validation in human knee condyles. Arthroscopy 2012; 28: 1513-1523
  • 102 Novakofski KD, Williams RM, Fortier LA et al. Identification of cartilage injury using quantitative multiphoton microscopy. Osteoarthritis Cartilage 2014; 22: 355-362
  • 103 Konig K, Speicher M, Kohler MJ et al. Clinical application of multiphoton tomography in combination with high-frequency ultrasound for evaluation of skin diseases. J Biophotonics 2010; 3: 759-773
  • 104 Collins DH. The Pathology of Articular and Spinal Diseases. London: Edward Arnold & Co; 1949
  • 105 Goebel L, Orth P, Müller A et al. Experimental scoring systems for macroscopic articular cartilage repair correlate with the MOCART score assessed by a high-field MRI at 9.4 T–comparative evaluation of five macroscopic scoring systems in a large animal cartilage defect model. Osteoarthritis Cartilage 2012; 20: 1046-1055
  • 106 Brittberg M, Lindahl A, Nilsson A et al. Treatment of deep cartilage defects in the knee with autologous chondrocyte transplantation. N Engl J Med 1994; 331: 889-895
  • 107 Knutsen G, Engebretsen L, Ludvigsen TC et al. Autologous chondrocyte implantation compared with microfracture in the knee. A randomized trial. J Bone Joint Surg Am 2004; 86-A: 455-464
  • 108 Saris DB, Vanlauwe J, Victor J et al. Characterized chondrocyte implantation results in better structural repair when treating symptomatic cartilage defects of the knee in a randomized controlled trial versus microfracture. Am J Sports Med 2008; 36: 235-246
  • 109 Rutgers M, van Pelt MJ, Dhert WJ et al. Evaluation of histological scoring systems for tissue-engineered, repaired and osteoarthritic cartilage. Osteoarthritis Cartilage 2010; 18: 12-23
  • 110 Orth P, Zurakowski D, Wincheringer D et al. Reliability, reproducibility, and validation of five major histological scoring systems for experimental articular cartilage repair in the rabbit model. Tissue engineering Part C, Methods 2012; 18: 329-339
  • 111 Mankin HJ, Lippiello L. Biochemical and metabolic abnormalities in articular cartilage from osteo-arthritic human hips. J Bone Joint Surg Am 1970; 52: 424-434
  • 112 Pritzker KP, Gay S, Jimenez SA et al. Osteoarthritis cartilage histopathology: grading and staging. Osteoarthritis Cartilage 2006; 14: 13-29
  • 113 Custers RJ, Creemers LB, Verbout AJ et al. Reliability, reproducibility and variability of the traditional Histologic/Histochemical Grading System vs. the new OARSI Osteoarthritis Cartilage Histopathology Assessment System. Osteoarthritis Cartilage 2007; 15: 1241-1248
  • 114 Ostergaard K, Petersen J, Andersen CB et al. Histologic/histochemical grading system for osteoarthritic articular cartilage: reproducibility and validity. Arthritis Rheum 1997; 40: 1766-1771
  • 115 Ostergaard K, Andersen CB, Petersen J et al. Validity of histopathological grading of articular cartilage from osteoarthritic knee joints. Ann Rheum Dis 1999; 58: 208-213
  • 116 Saal A, Gaertner J, Kuehling M et al. Macroscopic and radiological grading of osteoarthritis correlates inadequately with cartilage height and histologically demonstrable damage to cartilage structure. Rheumatol Int 2005; 25: 161-168
  • 117 Bendele AM, Hulman JF. Effects of body weight restriction on the development and progression of spontaneous osteoarthritis in guinea pigs. Arthritis Rheum 1991; 34: 1180-1184
  • 118 Colombo C, Butler M, Hickman L et al. A new model of osteoarthritis in rabbits. II. Evaluation of anti-osteoarthritic effects of selected antirheumatic drugs administered systemically. Arthritis Rheum 1983; 26: 1132-1139
  • 119 Foland JW, McIlwraith CW, Trotter GW et al. Effect of betamethasone and exercise on equine carpal joints with osteochondral fragments. Vet Surg 1994; 23: 369-376
  • 120 Yagi R, McBurney D, Laverty D et al. Intrajoint comparisons of gene expression patterns in human osteoarthritis suggest a change in chondrocyte phenotype. J Orthop Res 2005; 23: 1128-1138
  • 121 OʼDriscoll SW, Keeley FW, Salter RB. The chondrogenic potential of free autogenous periosteal grafts for biological resurfacing of major full-thickness defects in joint surfaces under the influence of continuous passive motion. An experimental investigation in the rabbit. J Bone Joint Surg Am 1986; 68: 1017-1035
  • 122 Pineda S, Pollack A, Stevenson S et al. A semiquantitative scale for histologic grading of articular cartilage repair. Acta Anat (Basel) 1992; 143: 335-340
  • 123 Wakitani S, Goto T, Pineda SJ et al. Mesenchymal cell-based repair of large, full-thickness defects of articular cartilage. J Bone Joint Surg Am 1994; 76: 579-592
  • 124 Fujimoto E, Ochi M, Kato Y et al. Beneficial effect of basic fibroblast growth factor on the repair of full-thickness defects in rabbit articular cartilage. Arch Orthop Trauma Surg 1999; 119: 139-145
  • 125 Katayama R, Wakitani S, Tsumaki N et al. Repair of articular cartilage defects in rabbits using CDMP1 gene-transfected autologous mesenchymal cells derived from bone marrow. Rheumatology (Oxford) 2004; 43: 980-985
  • 126 Nagura I, Fujioka H, Kokubu T et al. Repair of osteochondral defects with a new porous synthetic polymer scaffold. J Bone Joint Surg Br 2007; 89: 258-264
  • 127 Namba RS, Meuli M, Sullivan KM et al. Spontaneous repair of superficial defects in articular cartilage in a fetal lamb model. J Bone Joint Surg Am 1998; 80: 4-10
  • 128 Otsuka Y, Mizuta H, Takagi K et al. Requirement of fibroblast growth factor signaling for regeneration of epiphyseal morphology in rabbit full-thickness defects of articular cartilage. Dev Growth Differ 1997; 39: 143-156
  • 129 Sellers RS, Peluso D, Morris EA. The effect of recombinant human bone morphogenetic protein-2 (rhBMP-2) on the healing of full-thickness defects of articular cartilage. J Bone Joint Surg Am 1997; 79: 1452-1463
  • 130 Ylanen HO, Helminen T, Helminen A et al. Porous bioactive glass matrix in reconstruction of articular osteochondral defects. Ann Chir Gynaecol 1999; 88: 237-245
  • 131 Mainil-Varlet P, Aigner T, Brittberg M et al. Histological assessment of cartilage repair: a report by the Histology Endpoint Committee of the International Cartilage Repair Society (ICRS). J Bone Joint Surg Am 2003; 85-A (Suppl. 02) 45-57
  • 132 Mainil-Varlet P, Van Damme B, Nesic D et al. A new histology scoring system for the assessment of the quality of human cartilage repair: ICRS II. Am J Sports Med 2010; 38: 880-890
  • 133 Rolauffs B, Williams JM, Grodzinsky AJ et al. Distinct horizontal patterns in the spatial organization of superficial zone chondrocytes of human joints. J Struct Biol 2008; 162: 335-344
  • 134 Aicher WK, Rolauffs B. The spatial organisation of joint surface chondrocytes: review of its potential roles in tissue functioning, disease and early, preclinical diagnosis of osteoarthritis. Ann Rheum Dis 2014; 73: 645-653
  • 135 Rolauffs B, Rothdiener M, Bahrs C et al. Onset of preclinical osteoarthritis: the angular spatial organization permits early diagnosis. Arthritis Rheum 2011; 63: 1637-1647
  • 136 Rolauffs B, Williams JM, Aurich M et al. Proliferative remodeling of the spatial organization of human superficial chondrocytes distant from focal early osteoarthritis. Arthritis Rheum 2010; 62: 489-498
  • 137 Meinhardt M, Luck S, Martin P et al. Modeling chondrocyte patterns by elliptical cluster processes. J Struct Biol 2012; 177: 447-458
  • 138 Bertrand J, Cromme C, Umlauf D et al. Molecular mechanisms of cartilage remodelling in osteoarthritis. Int J Biochem Cell Biol 2010; 42: 1594-1601
  • 139 Heinegård D, Saxne T. The role of the cartilage matrix in osteoarthritis. Nat Rev Rheumatol 2011; 7: 50-56
  • 140 Madry H, Luyten FP, Facchini A. Biological aspects of early osteoarthritis. Knee Surg Sports Traumatol Arthrosc 2012; 20: 407-422
  • 141 Andriacchi TP, Mundermann A, Smith RL et al. A framework for the in vivo pathomechanics of osteoarthritis at the knee. Ann Biomed Eng 2004; 32: 447-457
  • 142 Houard X, Goldring MB, Berenbaum F. Homeostatic mechanisms in articular cartilage and role of inflammation in osteoarthritis. Curr Rheumatol Rep 2013; 15: 375
  • 143 Goldring MB, Otero M. Inflammation in osteoarthritis. Curr Opin Rheumatol 2011; 23: 471-478
  • 144 Sandell LJ, Aigner T. Articular cartilage and changes in arthritis. An introduction: cell biology of osteoarthritis. Arthritis Res 2001; 3: 107-113
  • 145 Mankin HJ, Dorfman H, Lippiello L et al. Biochemical and metabolic abnormalities in articular cartilage from osteo-arthritic human hips. II. Correlation of morphology with biochemical and metabolic data. J Bone Joint Surg Am 1971; 53: 523-537
  • 146 Brama PA, Tekoppele JM, Bank RA et al. Functional adaptation of equine articular cartilage: the formation of regional biochemical characteristics up to age one year. Equine Vet J 2000; 32: 217-221
  • 147 Howell DS. Pathogenesis of osteoarthritis. Am J Med 1986; 80: 24-28
  • 148 Hamerman D. The biology of osteoarthritis. N Engl J Med 1989; 320: 1322-1330