This is a disease mainly of the cartilage, but also the subchondral bone. If you look at the joint, and some like to think of osteoarthritis as a total joint failure. Again, it’s not a real synovial process but it probably starts in the cartilage. The cartilage is made up of chondrocytes, which are these little circles, then you have your proteoglycans which are very hygroscopic. They hold water in a gel state and give the cartilage its resiliency. And cartilage would expand even more if it wasn’t for this sort of retaining collagen framework that laces back and forth through the cartilage to give it some structure. It’s believed that the initial insult is some kind of damage to this collagen. Maybe what happens then is that when the collagen starts to break down these proteoglycans start to absorb more and more water, the cartilage begins to swell and it loses its typical helpful resilience. Once that is out of balance then the chondrocytes become injured and the cartilage does start to finally degrade. But often these patients have abnormalities of the subchondral bone, probably initially starting in the cartilage. The subchondral bone is not exactly like the rest of the bony structures. It’s designed to absorb some impact and if it starts to sclerose it’s not going to do a very good job of that. The last thing, that’s not shown in this slide, are these neurologic and mechanical factors. Any abnormalities of the ligaments, any alteration of the biomechanics of the joint because of muscle weakness or neurologic impairment, albeit subtle, may actually aggravate the pressure on the cartilage, accelerating the damage. Occasionally patients will have osteoarthritis and then they’ll sprain an ankle or twist a knee, nothing bad enough to require a cast or surgery, but then what you may notice is in that joint the osteoarthritis accelerates because of these probably subtle biomechanical changes.
If you look at it just in a schematic way, abnormalities of the collagen network, for whatever reason, swelling of the cartilage resulting in chondrocyte injury. Like most cells in the body, if the cells become injured, they try to somehow repair. So they actually have what we call “synthetic response”. They produce more of the matrix proteins. They also start to produce more of the proteolytic enzymes. There’s a balance between production of these matrix proteins and destruction. What may also be part of the picture, is that eventually when the chondrocytes can’t keep up the destructive enzymes start to get the upper hand, and finally when the cartilage breaks down you lose your chondrocytes. It’s not the kind of tissue that can repair itself. It’s not like skin or liver. Once it’s damaged to a certain point it does not recover. It doesn’t have any vascular supply. All its nutrients come from blood vessels or synovium so it really has a limited ability to repair. Again, you see that once the cartilage breaks down, that may lead to changes in biomechanical factors but the biomechanical factors may also have an initiating role, or aggravating role, so it becomes a vicious cycle and ultimately the patients develop osteophytes and the like.
Probably about 60 million people have x-ray evidence of osteoarthritis in this county. Any country that has a significant older population, it’s a significant problem. Obviously if you go to a country where the average life span is 45, I don’t think osteoarthritis is going to be on the top of their list of things to treat. But in this country it is a very significant medical problem. It’s not life-threatening, in a sense, but it certainly can be very disabling. I think 500 years ago osteoarthritis probably was a cause of death. People couldn’t keep up, they couldn’t work in the fields or whatever it is that they did, and basically if you didn’t work you didn’t eat and you were just sort of left to die if the culture you were in didn’t have the ability to care for you. In our culture we do, but it is a major health problem, major expense. Over half a million joint replacements are done every year and probably better than 90% of those are done for osteoarthritis. If you think how much these things cost – and also there is some morbidity, occasionally mortality, it’s not a benign procedure – but I’ll tell you the surgeons are getting really good. Most of the patients I see are out in two or three days unless they have a lot of other medical or arthritis problems to go on with it. They just get all their stuff at home, their low molecular heparin and physical therapy all at home. A lot of these patients, of the 60 million that I quoted, may just have x-ray evidence. If you do x-rays of people that are 80 years or older you are going to see a lot of osteophytes, maybe you’ll see some cartilage loss. A lot of these patients really won’t have many symptoms. I’m sure you all have done a flat plate of the abdomen or a chest x-ray, or an x-ray of a knee that got banged up, and you see a little bit of osteoarthritis that is really of no clinical significance. It would be of clinical significance if we had some kind of therapy to prevent progression. But since we don’t, it’s of little importance.
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