Osteoarthritis – causes, symptoms, diagnosis, treatment & pathology

Osteoarthritis – causes, symptoms, diagnosis, treatment & pathology


Osteo- means “bone”, and -arth- refers
to “arthron” which means joint, and -itis means “inflammation”, so osteoarthritis
is a disease involving inflammation of the bone and joint cartilage. It was once thought that the “itis” part
of osteoarthritis was a misnomer, and that inflammation didn’t play a role in its development,
and that it was mostly a degenerative disease resulting from simple “wear and tear”. Nowadays, it’s thought that inflammation
does indeed play an important role in the development of osteoarthritis. Alright, so a healthy joint consists of two
bones, each with its own layer of articular cartilage, which is a type of connective tissue
that allows the two bones to glide against each other essentially without friction. With Osteoarthritis, we’re really talking
about one particular kind of joint which is a synovial joint. Along with articular cartilage, another important
component of synovial joints, and where they get their name from, is the synovium, which
along with the surface of the articular cartilage, forms the inner lining of the joint space. The synovium’s composed of loose connective
tissue, blood vessels, lymphatic vessels, and on the surface—”Type A” cells that
clear cellular debris and “Type B” cells that produce components of synovial fluid,
which helps lubricate the two articular surfaces. One of the main issues in osteoarthritis is
the progressive loss of this articular cartilage, which means there’s not much separating
the two bones anymore, which adds a significant amount of friction between them, which then
generates inflammation, and triggers pain through the nerve endings in this joint space. Maintaining healthy articular cartilage is
the chondrocyte’s job, a specialized cell responsible for maintaining everything cartilage-related. The chondrocytes produce and are embedded
within a strong gel or extracellular matrix which contains type II collagen, a protein
that provides structural support, as well as proteoglycans, which are aggregates of
protein and sugar molecules like as hyaluronic acid, chondroitin sulfate, and keratin sulfate. All of these extracellular components give
the cartilage elasticity and high tensile strength, which help weight-bearing joints
distribute weight such that the underlying bone absorbs the shock and weight, and these
are joints like the knees, hips, and the lower lumbar spine. Okay, so chondrocytes are important for the
articular cartilage, got it. That makes sense. In healthy people, chondrocytes maintain a
delicate balance between breaking down old cartilage—called catabolic activity, and
producing new cartilage—called anabolic activity, through the use of both degradative
enzymes and synthetic enzymes. When something causes an increased expression
of degradative enzymes, then the balance tips toward a net loss of cartilage, via loss of
proteoglycans and collagen. What sort of something though can cause an
increased expression of degradative enzymes? That’s the million dollar question, right? And the answer isn’t super straight forward. The biggest risk factor for osteoarthritis
seems to be age, and often the cartilage degrades over longer periods of time, which makes it
really hard to pinpoint one single culprit. As I mentioned earlier, inflammation also
seems to be involved, and there are a number of proinflammatory cytokines like IL-1, IL-6,
and TNF, among others, that seem to play a role. Some of these are more involved in breaking
down cartilage through proteolysis, meaning increased catabolism, whereas others are more
involved in blocking the formation of new cartilage (meaning decreased anabolism). Also, joint injury, which brings with it a
lot of inflammation, seems to be a major risk factor for osteoarthritis, as well as mechanical
stress and obesity. Other risk factors include neurologic disorders,
genetic factors, and even certain medications, suggesting there are other mechanisms at play
as well. Whatever the initial cause of articular cartilage
damage is, it gets the chondrocytes to start trying to repair the cartilage. They initially start making less of the proteoglycans
and more Type II collagen, but soon switch over to making a different collagen type,
type I collagen. Unfortunately, type I collagen doesn’t interact
with the proteoglycans in the same way and there is an overall decrease in elasticity
in the cartilage matrix, allowing it to breakdown. Eventually though, over the course of years,
chondrocytes aren’t able to keep up, and they become exhausted, and can undergo apoptosis,
or programmed cell death. The cartilage gets softer, weaker, and continues
to lose elasticity, and starts to flake off into the synovial space, called joint mice. As “type A” cells in the synovium attempt
to remove the debris, immune cells like lymphocytes and macrophages are recruited into the synovial
membrane, which produces proinflammatory cytokines that ultimately cause inflammation of the
synovium as well, called synovitis. Also, fibrillations form, essentially these
cracks or clefts, on what used to be a smooth articular surface. The cartilage continues to erode away until
the bone’s exposed, allowing it to rub with the other bone, which causes bone eburnation,
making it look like polished ivory. Finally, on the edges, bone grows outward,
called osteophytes, which makes the joints look wider, something that’s most obvious
when seen in the distal and proximal interphalangeal joints, or the finger joints, called Heberden
nodes in the distal joint and Bouchard nodes in the proximal. Osteoarthritis is really common, and nearly
everyone knows someone that suffers from it. People with osteoarthritis often feel stiffness
in the morning, which usually lasts less than 1 hour but comes back at the end of the day. This is an important difference between rheumatoid
arthritis, an inflammatory disease that also affects the joints. With rheumatoid arthritis, morning stiffness
usually lasts longer than 1 hour. The pain in osteoarthritis is usually a sharp
ache or burning sensation, which also gets worse with prolonged activity, but usually
the joints don’t swell, whereas rheumatoid arthritis typically involves painful swelling. Finally, management and treatment of osteoarthritis
can involve non-pharmacological approaches, like losing weight or moderate exercise, as
well as physical therapy. This can be especially important for large-weight
bearing joints like the hips and knees. Pharmacological treatments focus on reducing
pain and inflammation. If neither of these approaches are successful,
sometimes people might benefit from injections of hyaluronic acid into the joint or may need
surgery to replace the affected joint.

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