John E.F. Houlton, MA, VetMB, DVR, DSAO, DECVS
Disease of the cranial cruciate ligament (CCL) is the most common condition to affect the canine stifle joint yet still remains poorly understood. It is not a new disease, being first described by Carlin in 19261. Paatsama in 1952 undertook the first major study into the condition2 and since then there has been a plethora of papers describing its aetiology, pathogenesis and treatment.
CCL rupture occurs in all sizes of dogs but occurs more frequently in the larger breeds, and at a younger age. Recent epidemiological studies have indicated an increased prevalence of CCL disease in certain breeds such as the Rottweiler, Newfoundland and Labrador Retriever.3,4 In contrast, the breed that was over-represented in Paatsama's thesis was the Scottie.
The CCL contains twisted collagenous fascicles and fibre bundles, is narrowest in its mid-region, and fans out proximally and distally. Its shape changes during normal motion, accentuating this narrow mid-region. Both cruciate ligaments are covered by a fairly uniform fold of synovial membrane which incompletely divides the stifle joint in the sagittal plane. This synovial tissue consists mainly of dense connective tissue, small fibroblasts and some adipocytes. Compared with the cruciate ligaments, the enveloping synovial membrane is relatively cellular. Importantly, the membrane makes the CCL an extrasynovial structure, protecting it from the degradative effects of the synovial environment.
Immune mediated phenomena have been suggested by a number of authors as a factor in CCL disease. Because the intact CCL is extrasynovial, collagen type I is normally obscured from immunologic surveillance and therefore has the potential to act as a self-antigen.5 There is also a school of thought that the production of matrix degrading enzymes by the synovium induces progressive pathologic rupture of the CCL.6
The synovial membrane together with the infrapatellar fat pad is the most important source of blood vessels. These arborise into a fine mesh of vessels ensheathing the CCL throughout its entire length. The inner portion of the CCL contains an endoligamentous vascular supply--the two anastamosing. There are numerous endosteal vessels but communications with the endoligamentous vessels is poor, especially at the tibial attachment of the CCL. It has been postulated that vascular mechanisms play a role in CCL rupture, especially as the blood supply to the core region is marginal and hypoxia may weaken it.7
Nerves of differing sizes are located in the synovial membrane covering the cruciate ligaments. It is believed that their function is primarily associated with autonomic nervous regulation of blood flow and pain perception. Mechanoreceptors are found particularly at the proximal end of the CCL, while the distal third is sparsely populated. These mechanoreceptors activate local reflexes to protect the ligament from non-physiological loads. The CCL-muscle reflex triggers periarticular muscles, thus contributing to the functional stability of the stifle. It is not a matter of conscious proprioception but more a mechanically evoked electrical signalling system.
Ultrastructurally, the CCL is a heterogenic composite structure formed by extracellular matrix composed of macromolecules, the major of these being collagen type I, comprising >90% of the collagen content, with the remainder being type III. The molecules are produced by the fibroblasts in the loose supporting connective tissue. The cells are present in long parallel columns between the collagen fibres. Neurovascular components follow the same longitudinal orientation. In addition to the fibroblasts there are chondrocyte-like cells.
Comerford et al examined the ultrastructure of CCLs from the Labrador Retriever, a breed with a known propensity for CCL rupture, and compared these to the Greyhound, a low-risk breed.8,9 Histological examination revealed a "fibrocartilaginous" appearance of CCLs in seven of eight greyhounds and to a lesser extent in three of eight Labrador retrievers. This suggests that the formation of fibrocartilage is not a disadvantage to the healthy racing greyhound. Whether the same holds true for the Labrador retriever is debatable. Using transmission electron microscopy to assess collagen fibril diameter, the same authors found that the mean fibril diameter in the Labrador is significantly smaller than that of the Greyhound. In previous experimental work, Zachos et al demonstrated the collagen fibril diameter of the caudal cruciate ligament decreased following CCL transection.10 Both studies suggest that collagen fibril diameter is a marker for altered loading.
There is data to suggest that collagen turnover in CCLs from at-risk breeds is increased compared to low-risk breeds. Tissue concentrations of gelatinase (matrix metalloproteinase-2 [MMP-2]) are upregulated in the at-risk breeds compared to controls. Additionally, concentrations of tissue inhibitor of MMPs (TIMP-2) are lower in the at-risk breeds compared to controls. Furthermore, cross-linking profiles of collagen disease show more intermediate collagen cross-links in at risk-breeds compared to controls.11 Whether increased collagen turnover in CCLs from at-risk breeds is constitutive, or induced is unknown. Thus one has to ask the question, are any observed changes part of the repair process or did they precede ligament rupture?
Connective tissue metabolism has been shown to be influenced by oestrogens. Female human athletes are more prone to anterior cruciate ligament rupture compared to male athletes, while in rabbits, oestrogen has been shown to downregulate metabolism of CCL cells in vitro. Furthermore, oestrogen has been reported to decrease collagen synthesis in the human anterior cruciate ligament. Oestrogen receptors have been demonstrated on the surface of ACL cells.
Neutering in dogs has been shown to increase the risk of CCL disease. This apparent anomaly in the relevance of hormonal status may be related to increased bodyweight and obesity, and further work is required in this area.
In recent years, the tibial plateau has been a subject of much debate. One study suggests that dogs with CCL rupture have an excessive slope to the tibial plateau12 but others have failed to substantiate this. Wilke and colleagues measured traditional and standing tibial plateau angles (TPA) in affected and unaffected Labradors and unaffected Greyhounds.13 The authors concluded that although TPA may be associated with damage to the cruciate ligaments, many dogs with a steep TPA do not develop cruciate ligament disease. It has also been suggested that if the patellar ligament is perpendicular to the tibial plateau, there is no shear component of the total joint force of weight bearing and the CCL is no longer loaded.
Colborne et al have published studies on the in vivo biomechanics of the normal Greyhound and normal Labrador14 using a combination of kinetic, kinematic and morphometric measures to estimate the moments, work and power acting through the stifle joint. Consistent differences between these two breeds of dog were demonstrated. The peak cranial caudal force acting through the stifle joint at the trot (the force that the CCL must resist) was greater in the Labrador than in the Greyound.
From the above, it is clear that there are many unanswered questions regarding the aetiology and pathogenesis of CCL rupture. The same also applies to its management. The number of recommended repair techniques runs well into three figures and shows no sign of abating. Intra-articular grafts, extra-capsular suture stabilisation and proximal tibial osteotomy techniques are currently recommended. Tibial osteotomy techniques do not attempt to provide stability of the stifle but alter joint geometry to eliminate cranial tibial thrust. Thus functional joint stability is achieved during weight bearing. It seems universally accepted that whatever technique is employed, meniscal pathology must be addressed. What is less clear is whether some form of release technique is necessary, or advisable, when performing tibial osteotomy techniques.
An area of emerging interest, and perhaps one that will render the choice of surgical procedure irrelevant, is the post-operative management of these dogs. It should be an integral part of CCL rupture treatment and the benefits of physiotherapy, including hydrotherapy in its various forms, needs to be scientifically evaluated.
Finally, the inevitable question has to be "which technique is best?" It has become fashionable to use evidence based medicine (EBM) to assist clinicians with the decision-making process for a variety of clinical problems. The definition of EBM was initially directed at the conscientious, explicit, and judicious use of current best evidence in making decisions about the care of individual patients. It has subsequently evolved to include the integration of individual clinical expertise, patient values, and the best available clinical evidence from systematic research. Level 1 evidence is likely to be optimally achieved through three methods of evaluation: i) force plate analysis, ii) subjective and objective evaluation by the clinician, and iii) subjective evaluation by the pet owner. However, while there is some agreement on what is an appropriate method for i), there is absolutely none for ii) and iii).
Aragon & Budsberg using EBM concluded in a somewhat damning fashion "there is not a single surgical procedure that has enough data to recommend it can consistently return dogs to normal function after CCL injury".15 This, despite canine cruciate repair costing 1.23 billion dollars every year in the United States and the incidence of cruciate surgery in dogs exceeding that in humans.
References
1. Carlin I: Ruptur des ligamentum cruciatum anterius im Kniegelenk beim Hund. Arch f. Wissenench u. Prakt. Tierheilk 54, 420 (1926)
2. Paatsama S: Ligament injuries of the canine stifle joint; a clinical and experimental study. Thesis, Helsinki (1952)
3. Whitehair JG, Vasseur PB, Willits NH: Epidemiology of cranial cruciate ligament rupture in dogs. Journal of the American Animal Hospital Association 203:1016-1019, 1993
4. Doverspike M, Vasseur PB, Harb MF, Walls CM: Contralateral cranial cruciate ligament rupture: incidence in 114 dogs. Journal of the American Animal Hospital Association 29:167-170, 1993
5. De Rooster H, Cox E & van Bree H: Prevalence and relevance of antibodies to type I and II collagen in synovial fluid of dogs with cranial cruciate ligament damage. American Journal Veterinary Research 61: 1456-1461, 2000
6. Muir P, Schamberger GM, Manley PA, Hao ZL: Localization of cathepsin K and tartrate-resistant acid phosphatase in synovium and cranial cruciate ligament in dogs with cruciate disease. Veterinary Surgery 34:239-246, 2005
7. Hayashi K, Frank JD, Dubinsky C et al: Histologic changes in ruptured canine cranial cruciate ligament. Veterinary Surgery 32: 269-277, 2003
8. Comerford EJ, Tarlton JF, Wales A, Bailey AJ, Innes JF: Ultrastructural Differences in Cranial Cruciate Ligaments from Dogs of Two Breeds with a Differing Predisposition to Ligament Degeneration and Rupture. Journal of Comparative Pathology, 134, 8-16, 2005
9. Comerford EJ, Tarlton JF, Innes JF, Johnson KA, Amis AA, Bailey AJ: Metabolism and composition of the canine anterior cruciate ligament relate to differences in knee joint mechanics and predisposition to ligament rupture. Journal of Orthopaedic Research 23:61-66, 2005
10. Zachos TA, Arnoczky SP, Lavagnino M, Tashman S: The effect of cranial cruciate ligament insufficiency on caudal cruciate ligament morphology: An experimental study in dogs. Veterinary Surgery 31:596-603, 2002
11. Comerford EJ, Innes JF Tarlton JF & Bailey AJ,: Investigation of the composition, turnover, and thermal properties of ruptured cranial cruciate ligaments in dogs: American Journal Veterinary Research: 65, 1136-1141, 2004
12. Morris E, Lipowitz AJ: Comparison of tibial plateau angles in dogs with and without cranial cruciate ligament injuries. Journal of the American Veterinary Medical Association 218:363-366, 2001
13. Wilke VL, Conzemius MG, Besancon ME, Evans RB, Ritter M: Comparison of tibial plateau angle between clinically normal Greyhounds and Labrador Retrievers with and without rupture of the cranial cruciate ligament. Journal of the American Veterinary Medical Association 221:1426-1429, 2002
14. Colborne GR, Innes JF, Comerford EJ, Owen MR, Fuller CJ: Distribution of power across the hind limb joints in Labrador Retrievers and Greyhounds. American Journal of Veterinary Research 66:1563-1571, 2005
15. Aragon CL, Budsberg SC: Applications of Evidence-Based Medicine: Cranial Cruciate Ligament Injury Repair in the Dog. Veterinary Surgery 34: 93-98, 2005