Anterior cruciate ligament changes in the human knee joint in aging and osteoarthritis
Akihiko Hasegawa
The Scripps Research Institute, La Jolla, California
Search for more papers by this authorShuhei Otsuki
The Scripps Research Institute, La Jolla, California
Search for more papers by this authorChantal Pauli
The Scripps Research Institute, La Jolla, and Scripps Clinic in San Diego, La Jolla, California
Search for more papers by this authorShigeru Miyaki
The Scripps Research Institute, La Jolla, California
Search for more papers by this authorMitsuo Kinoshita
Osaka Medical College, Osaka, Japan
Osaka Medical College, Osaka, Japan
Search for more papers by this authorJames Koziol
The Scripps Research Institute, La Jolla, California
Search for more papers by this authorDarryl D. D'Lima
The Scripps Research Institute, La Jolla, and Scripps Clinic in San Diego, La Jolla, California
Search for more papers by this authorCorresponding Author
Martin K. Lotz
The Scripps Research Institute, La Jolla, California
Department of Molecular and Experimental Medicine, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037Search for more papers by this authorAkihiko Hasegawa
The Scripps Research Institute, La Jolla, California
Search for more papers by this authorShuhei Otsuki
The Scripps Research Institute, La Jolla, California
Search for more papers by this authorChantal Pauli
The Scripps Research Institute, La Jolla, and Scripps Clinic in San Diego, La Jolla, California
Search for more papers by this authorShigeru Miyaki
The Scripps Research Institute, La Jolla, California
Search for more papers by this authorMitsuo Kinoshita
Osaka Medical College, Osaka, Japan
Osaka Medical College, Osaka, Japan
Search for more papers by this authorJames Koziol
The Scripps Research Institute, La Jolla, California
Search for more papers by this authorDarryl D. D'Lima
The Scripps Research Institute, La Jolla, and Scripps Clinic in San Diego, La Jolla, California
Search for more papers by this authorCorresponding Author
Martin K. Lotz
The Scripps Research Institute, La Jolla, California
Department of Molecular and Experimental Medicine, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037Search for more papers by this authorAbstract
Objective
The development and patterns of spontaneous age-related changes in the anterior cruciate ligament (ACL) and their relationship to articular cartilage degeneration are not well characterized. This study was undertaken to investigate the types and temporal sequence of age-related ACL changes and to determine their correlation with cartilage lesion patterns at all stages of osteoarthritis (OA) development in human knee joints without prior joint trauma.
Methods
Human knee joints (n = 120 from 65 donors ages 23–92) were obtained at autopsy, and ACLs and cartilage were graded macroscopically and histologically. Inflammation surrounding the ACL was assessed separately.
Results
Histologic ACL substance scores and ligament sheath inflammation scores increased with age. Collagen fiber disorganization was the earliest and most prevalent change. The severity of mucoid degeneration and chondroid metaplasia in the ACL increased with the development of cartilage lesions. A correlation between ACL degeneration and cartilage degeneration was observed, especially in the medial compartment of the knee joint.
Conclusion
Our findings indicate that ACL degeneration is highly prevalent in knees with cartilage defects and may even precede cartilage changes. Hence, ACL deficiencies may not only be important in posttraumatic OA, but may also be a feature associated with knee OA pathogenesis in general.
REFERENCES
- 1 Felson DT, Lawrence RC, Dieppe PA, Hirsch R, Helmick CG, Jordan JM, et al. Osteoarthritis: new insights. Part 1: the disease and its risk factors. Ann Intern Med 2000; 17;133: 635–46.
- 2 Felson DT, Zhang Y, Hannan MT, Naimark A, Weissman B, Aliabadi P, et al. Risk factors for incident radiographic knee osteoarthritis in the elderly: the Framingham Study. Arthritis Rheum 1997; 40: 728–33.
- 3 Hunter DJ, Zhang Y, Niu J, Tu X, Amin S, Goggins J. Structural factors associated with malalignment in knee osteoarthritis: the Boston osteoarthritis knee study. J Rheumatol 2005; 32: 2192–9.
- 4 Cooper C, Snow S, McAlindon TE, Kellingray S, Stuart B, Coggon D, et al. Risk factors for the incidence and progression of radiographic knee osteoarthritis. Arthritis Rheum 2000; 43: 995–1000.
- 5 Bennett LD, Buckland-Wright JC. Meniscal and articular cartilage changes in knee osteoarthritis: a cross-sectional double-contrast macroradiographic study. Rheumatology (Oxford) 2002; 41: 917–23.
- 6 Hill CL, Seo GS, Gale D, Totterman S, Gale ME, Felson DT. Cruciate ligament integrity in osteoarthritis of the knee. Arthritis Rheum 2005; 52: 794–9.
- 7 Bergin D, Keogh C, O'Connell M, Rowe D, Shah B, Zoga A, et al. Atraumatic medial collateral ligament oedema in medial compartment knee osteoarthritis. Skeletal Radiol 2002; 31: 14–8.
- 8 Nichols EH, Richardson FL. Arthritis deformans. J Med Res 1909; 21: 149–222.51.
- 9 Lohmander LS, Englund PM, Dahl LL, Roos EM. The long-term consequence of anterior cruciate ligament and meniscus injuries: osteoarthritis. Am J Sports Med 2007; 35: 1756–69.
- 10 Fleming BC, Hulstyn MJ, Oksendahl HL, Fadale PD. Ligament injury, reconstruction and osteoarthritis. Curr Opin Orthop 2005; 16: 354–62.
- 11 Woo SL, Livesay GA, Engle C. Biomechanics of the human anterior cruciate ligament: muscle stabilization and ACL reconstruction. Orthop Rev 1992; 21: 935–41.
- 12 Fleming BC. Biomechanics of the anterior cruciate ligament. J Orthop Sports Phys Ther 2003; 33: A13–5.
- 13 Louboutin H, Debarge R, Richou J, Selmi TA, Donell ST, Neyret P, et al. Osteoarthritis in patients with anterior cruciate ligament rupture: a review of risk factors. Knee 2009; 16: 239–44.
- 14 Mullaji AB, Marawar SV, Simha M, Jindal G. Cruciate ligaments in arthritic knees: a histologic study with radiologic correlation. J Arthroplasty 2008; 23: 567–72.
- 15 Chaudhari AM, Zelman EA, Flanigan DC, Kaeding CC, Nagaraja HN. Anterior cruciate ligament-injured subjects have smaller anterior cruciate ligaments than matched controls: a magnetic resonance imaging study. Am J Sports Med 2009; 37: 1282–7.
- 16 Bergin D, Morrison WB, Carrino JA, Nallamshetty SN, Bartolozzi AR. Anterior cruciate ligament ganglia and mucoid degeneration: coexistence and clinical correlation. AJR Am J Roentgenol 2004; 182: 1283–7.
- 17 Fernandes JL, Viana SL, Mendonca JL, Freitas FM, Bezerra AS, Lima GA, et al. Mucoid degeneration of the anterior cruciate ligament: magnetic resonance imaging findings of an underdiagnosed entity. Acta Radiol 2008; 49: 75–9.
- 18 Trompeter AJ, Gill K, Appleton MA, Palmer SH. Predicting anterior cruciate ligament integrity in patients with osteoarthritis. Knee Surg Sports Traumatol Arthrosc 2009; 17: 595–9.
- 19 Cushner FD, La Rosa DF, Vigorita VJ, Scuderi GR, Scott WN, Insall JN. A quantitative histologic comparison: ACL degeneration in the osteoarthritic knee. J Arthroplasty 2003; 18: 687–92.
- 20 Minino A, Xu J, Kochanek K, Tejada-Vera B. Death in the United States, 2007. NCHS Data Brief 2009; 26: 1–8.
- 21 Allain J, Goutallier D, Voisin MC. Macroscopic and histological assessments of the cruciate ligaments in arthrosis of the knee. Acta Orthop Scand 2001; 72: 266–9.
- 22 Kennedy JC, Weinberg HW, Wilson AS. The anatomy and function of the anterior cruciate ligament: as determined by clinical and morphological studies. J Bone Joint Surg Am 1974; 56: 223–35.
- 23 Wang IE, Mitroo S, Chen FH, Lu HH, Doty SB. Age-dependent changes in matrix composition and organization at the ligament-to-bone insertion. J Orthop Res 2006; 24: 1745–55.
- 24 Krenn V, Morawietz L, Haupl T, Neidel J, Petersen I, Konig A. Grading of chronic synovitis—a histopathological grading system for molecular and diagnostic pathology. Pathol Res Pract 2002; 198: 317–25.
- 25 Outerbridge RE. The etiology of chondromalacia patellae. J Bone Joint Surg Br 1961; 43-B: 752–7.
- 26 ICRS Cartilage Evaluation Package. 2000. URL: http://www.cartilage.org/_files/contentmanagement/ICRS_evaluation.pdf.
- 27 Link TM, Steinbach LS, Ghosh S, Ries M, Lu Y, Lane N, et al. Osteoarthritis: MR imaging findings in different stages of disease and correlation with clinical findings. Radiology 2003; 226: 373–81.
- 28 Hernigou P, Garabedian JM. Intercondylar notch width and the risk for anterior cruciate ligament rupture in the osteoarthritic knee: evaluation by plain radiography and CT scan. Knee 2002; 9: 313–6.
- 29 Leon HO, Blanco CE, Guthrie TB, Martinez OJ. Intercondylar notch stenosis in degenerative arthritis of the knee. Arthroscopy 2005; 21: 294–302.
- 30 Lee GC, Cushner FD, Vigoritta V, Scuderi GR, Insall JN, Scott WN. Evaluation of the anterior cruciate ligament integrity and degenerative arthritic patterns in patients undergoing total knee arthroplasty. J Arthroplasty 2005; 20: 59–65.
- 31 Wada M, Tatsuo H, Baba H, Asamoto K, Nojyo Y. Femoral intercondylar notch measurements in osteoarthritic knees. Rheumatology (Oxford) 1999; 38: 554–8.
- 32 Strocchi R, De Pasquale V, Facchini A, Raspanti M, Zaffagnini S, Marcacci M. Age-related changes in human anterior cruciate ligament (ACL) collagen fibrils. Ital J Anat Embryol 1996; 101: 213–20.
- 33 Wright T, Yoon C, Schmit BP. Shoulder MRI refinements: differentiation of rotator cuff tear from artifacts and tendonosis, and reassessment of normal findings. Semin Ultrasound CT MR 2001; 22: 383–95.
- 34 Buck FM, Grehn H, Hilbe M, Pfirrmann CW, Manzanell S, Hodler J. Degeneration of the long biceps tendon: comparison of MRI with gross anatomy and histology. AJR Am J Roentgenol 2009; 193: 1367–75.
- 35 Nelissen RG, Hogendoorn PC. Retain or sacrifice the posterior cruciate ligament in total knee arthroplasty? A histopathological study of the cruciate ligament in osteoarthritic and rheumatoid disease. J Clin Pathol 2001; 54: 381–4.
- 36 Salvati F, Rossi F, Limbucci N, Pistoia ML, Barile A, Masciocchi C. Mucoid metaplastic-degeneration of anterior cruciate ligament. J Sports Med Phys Fitness 2008; 48: 483–7.
- 37 Stubbs G, Dahlstrom J, Papantoniou P, Cherian M. Correlation between macroscopic changes of arthrosis and the posterior cruciate ligament histology in the osteoarthritic knee. ANZ J Surg 2005; 75: 1036–40.
- 38 Abreu M, Johnson K, Chung CB, De Lima JE Jr, Trudell D, Terkeltaub R, et al. Calcification in calcium pyrophosphate dihydrate (CPPD) crystalline deposits in the knee: anatomic, radiographic, MR imaging, and histologic study in cadavers. Skeletal Radiol 2004; 33: 392–8.
- 39 Murray MM, Spector M. Fibroblast distribution in the anteromedial bundle of the human anterior cruciate ligament: the presence of α-smooth muscle actin-positive cells. J Orthop Res 1999; 17: 18–27.
- 40 Murray MM, Weiler A, Spindler KP. Interspecies variation in the fibroblast distribution of the anterior cruciate ligament. Am J Sports Med 2004; 32: 1484–91.
- 41 Gillard GC, Reilly HC, Bell-Booth PG, Flint MH. The influence of mechanical forces on the glycosaminoglycan content of the rabbit flexor digitorum profundus tendon. Connect Tissue Res 1979; 7: 37–46.
