Review Question - QID 219829

The patient has bone-on-bone osteoarthritis of the knee, which, unlike normal cartilage aging, involves a decrease in articular aggrecan content and an increase in cellular permeability, with a subsequent increase in water content.

Early osteoarthritis (OA) produces damage to the collagen network of cartilage without a significant initial change in the proteoglycan content (i.e., aggrecans, heparan sulfate, keratan sulfate, etc). As the pathologic process continues and the numbers of these extracellular matrix components decline, cartilage then swells under the influence of the insufficiently restrained glycosaminoglycan side chains, producing a locally softer tissue with increased water content. These locally softer regions of tissue become further susceptible to damage during physiological loading, initiating the cascading effects of irreversible cartilage damage that leads to bone-on-bone arthritis.

Iannone et al. reviewed the pathophysiology of osteoarthritis. The authors note that OA is a complex disease whose pathogenesis includes alterations in the tissue homeostasis of articular cartilage and subchondral bone. Specifically, during OA, abnormal integrin expression alters cell signaling, allowing IL-1, TNF-alpha, and other pro-catabolic cytokines to activate the enzymatic degradation of the cartilage matrix. The authors conclude that the main enzymes involved in extracellular matrix breakdown are metalloproteinases (MMPs), which are sequentially activated by an amplifying cascade.

Mobasheri et al. provided an update on the pathophysiology of osteoarthritis. The authors reviewed a selection of 12,000 papers on the topic and found that there has been slow but steady progress in our understanding of the pathophysiology of OA over the last two decades. They concluded that large gaps remain in our knowledge of OA pathogenesis, which has an overall negative impact on patients and the drug development pipeline.

Figure 1 is an AP weight-bearing radiograph demonstrating bone-on-bone arthritis and prior ACL reconstruction.

Incorrect Answers:
Answers 1,2,4,5: The pathophysiologic process of osteoarthritis differs from that of normal aging and involves a decrease in aggrecans, an increase in cellular permeability, and an increase in overall water content, leading to hyaline cartilage softening and a cascade of irreversible destruction.