Degenerative Joint Disease

In the beginning of one’s professional education in most medical disciplines is a course in microscopic anatomy. One learns that hyaline cartilage is the tissue on which bones interface. One also learns that type II collagen of this tissue is extremely slow to turnover, that the proteoglycans important to binding water and maintaining the resilience of cartilage turn over rather rapidly, and that the chondrocytes responsible for all of this are extremely reluctant to proliferate. All this is combined with the astonishing fact that articular hyaline cartilage is avascular. Although most of us were in our twenties when learning these facts and not personally familiar with the creaks and pains of degenerative joint disease or its proposed mechanisms of development, we had doubts that these qualities of articular cartilage represented the best that evolution had to offer.

Most general textbooks present degenerative joint disease as a vicious cycle commencing with degeneration and necrosis of chondrocytes due to aging, excess/abnormal wear, or previous inflammation; a decreased content of matrix proteoglycan due to reduced chondrocyte production and accelerated loss from activation of latent matrix metalloproteinases; and/or erosion and collapse of collagen fibers due to a reduction of the hydrated gel of proteoglycans. Subsequent to this, in cases in which inflammation is not primary, sterile synovitis develops secondary to exposure to previously unrecognized breakdown products from the avascular cartilage. Increasing density of the subchondral bone (osteosclerosis) results from excessive mechanical forces penetrating the overlying defective cartilage. Most experts agree that once this cycle is created, each component can contribute to worsening of degenerative joint disease.

The cycle most often described in degenerative joint disease is that, in the beginning, the primary problem is the chondrocyte. This scenario is of a primary or idiopathic degenerative joint disease. In contrast, articular lesions are considered secondary in cases where the synovial inflammation (due to infection or a sterile immune response) occurs prior to degenerative joint disease.

Since the middle 1980s there has been speculation in human medicine that, in the beginning, before there is obvious cartilage degeneration, osteosclerosis develops in the subchondral bone due to increased mechanical force (eg, excess weight or excess use). Thus, osteosclerosis may play a role in the initiation of articular damage and subsequent degenerative joint disease.

The normal structure of subchondral bone and underlying trabecular bone has evolved to disperse concussive forces from the overlying joint onto the underlying medullary and cortical bone. If the subchondral bone is denser and therefore stiffer than normal, its ability to dissipate the load applied to the joint is altered, resulting in greater mechanical stress on the overlying chondrocytes. There is little doubt that stiffening of subchondral bone plays a role in the progression of degenerative joint disease; but whether, in the beginning, it is a primary initiating factor (at least in some joints) is still in question. ^1,2

The roles of synovial inflammation and cytokines in the progression of degenerative joint disease are not substantially different from those driving sterile immune-mediated and postinfectious arthritis. Still, the question is thus: In the beginning, is degenerative joint disease inflammatory? While most likely it is not (as supported by the morphologic data from an article in the current issue of the journal cited and discussed below), I have been intrigued, from first reading to the present, of a paper in 1981 from George Lust and Brian Summers. ⁴ They concluded, “Synovial inflammation with increased synovial fluid and ligament volumes were indicators of early degenerative joint disease in dogs. These changes seemed to coincide with, or perhaps to precede, microscopic evidence for articular degeneration and occurred before radiographic abnormalities were detected.” Their study was based on a colony of dogs predisposed to hip dysplasia. While these findings do not rule out inflammation being secondary to changes in cartilage that are inapparent morphologically, they support a hypothesis that inflammation might occur in degenerative joint disease much earlier than generally assumed. In addition, cytokines from inflammatory and structural cells within the joint may be responsible for changes previously thought to be secondary to mechanical instability. In 1994, Wim van den Berg and colleagues demonstrated that injection of transforming growth factor beta 1 into joints of normal mice induced osteophyte formation. ⁵

“Pathology of Articular Cartilage and Synovial Membrane from Elbow Joints with and without Degenerative Joint Disease in Domestic Cats,” by Mila Freire Gonzalez, Don Meuten, and Duncan Lascelles, is presented in this issue of the journal. ³ Who knew that domestic cats commonly develop degenerative joint disease? How would one know? It is like asking, what are the clinical signs of degenerative joint disease in sloths? While this article does not correlate lesions with clinical signs, the results confirm the findings of others that the lesion has high prevalence in cats—particularly in the elbow and most severely in its medial aspect. As one learns from references cited in the article, clinical signs are quite variable and usually manifest as an overall decrease in mobility rather than in a localized lameness. The authors present in great detail the morphology and distribution of lesions and make correlations among findings. Severity of inflammation did not correlate with the severity of other lesions and was therefore considered secondary. Most lesions of degenerative joint disease in cats are, as might be predicted, similar to those in other mammals. Strikingly, however, is the high incidence of synovial and osteochondral fragments in feline joints. The authors conclude, with justification, that this represents secondary synovial osteochondromatosis rather than a primary condition. It is the presence of such fragments in the elbow joints of cats (known from previous radiographic surveys) that prompted the authors to hypothesize the following: In the beginning, fragmentation through the osteochondral junction of the medial coronoid process is a predisposing factor for the development of degenerative joint disease in cats, as in dogs. Their data refute their hypothesis, and the authors conclude that in the beginning and to the end, fragmentation of the medial coronoid process is not a feature of degenerative joint disease in the feline elbows. The domestic cat appears to be a good model for the study of spontaneous degenerative joint disease, especially for those interested in the pathogenesis of secondary osteochondromatosis.