Hypothesis 1:

Ruptured cranial cruciate ligament, which can be caused by osteoarthritis, trauma / inconsistent exercise (chronic weight problems), age-related problems and/or immune-mediated ligament degeneration.


The cranial cruciate ligament (CrCL) is a fibrous connective tissue that connects the femur to the tibia, and affords stability to the stifle joint.  Because the CrCL is within the (confined) joint space, its integrity and functionality is dependent upon conditions within the joint.   These conditions may include: effusion and inflammation, immune-mediated destruction of tissues, and direct trauma to the bone and/or supporting connective tissues.

A low-grade osteoarthritis may result in significant enough stress on the CrCL to cause rupture, as the resultant increase in joint fluid and ligamentous changes may lead to decreased joint stability and increased laxity.  Osteoarthritis has numerous causes.  Regardless, a common pathogenesis prevails, involving a chronic, progressive insult to the articular cartilage of the femur and tibia. As the osteoarthritis progresses and the layers of the articular cartilage are damaged, the pro-inflammatory mediators (cytokines TNF-alpha and IL-1beta, prostaglandins, etc.) are released by synoviocytes.  This may possibly follow the phagocytosis of collagen and proteoglycan fragments (released upon trauma to the cartilage).  In response to the inflammatory mediators, the synovial lining undergoes hypertrophy and hyperplasia, and is accompanied by increased synovial vasculature permeability.  Synoviocytes produce increased low quality fluid (increased volume, decreased viscosity).  The subsynovial layer of the joint capsule will thicken, due to activity of fibroblasts.  The body is attempting to stabilize the joint, however, the increased fluid volume actually decreases joint stability and allows for luxation of the joint.  This subluxation stretches the fibrous joint capsule, causing additonal signs of pain and lameness.  Eventually, it is this decreased stability that increases the load on the CrCL, which has a known breaking strength.  Also, the pro-inflammatory mediators released by synoviocytes may act directly on the ligament. 

Obesity of an animal can predispose to both osteoarthritic changes and degeneration / rupture of the CrCL.   While a sedentary lifestyle can decrease mechanical strength of the CrCL with disuse, Bonnie is obese and moderately active.  We cannot postulate that disuse has decreased strength from the history given us by the owner.  The obesity, however, may contribute to an excessive force that can be greater than the breaking strength of the ligament.  In general, the breaking strength of the CrCL is approxiamately equal to four times the body weight of the dog. The CrCL is the primary stabilizer of the knee in extension and internal rotation.  Therefore, hyperextension or excessive rotation of the stifle, in addition to the excessive weight load, may lead to rupture of the ligament.   

Age related changes that may predispose CrCL rupture include an overall loss of fibroblasts, loss of structural organization of collagen fibers and primary collagen bundles, destruction of the parallel ligament bundles and an increase in areolar tissue near the ligament's insertion.  These degenerative lesions may explain why 20-40% of dogs with unilateral CrCL suffer subsequent rupture of the opposite CrCL.  This may be a possibility with Bonnie, because she demonstrates a laxity in the right stifle (2mM), as well.

Immune mediated arthritis may cause sufficient damage to the CrCL to predispose it to rupture.  Synovial macrophages or activated chondrocytes react to gamma immunoglobulins directed at the connective tissue and release proteases that degrade proteoglycans and collagen.  These proteases cause degeneration of the opsonized ligaments, cartilage and bone within the joint.   If the cranial cruciate ligament succumbs to this attack and degenerates, the end result is a decreased mechanical strength and ability of the ligament to withstand excessive forces.

In summary, the role of the CrCL in maintaining the tibia in position explains the clinical findings of our case.  Osteoarthritis, abberrant / excessive exercise, increased weight load, immune-mediated destruction of connective tissues and age-related changes all may predispose to rupture of the CrCL.  Once ruptured, abnormal movement of the tibia cranially, with respect to the femur, may explain Bonnie's cranial drawer sign.  CrCl rupture may also explain the difficulty Bonnie has with getting up and walking up stairs.  This difficulty may be manifested as pain and/ or decreased limb function.