What is the Pathophysiology of Osteoarthritis and what are the risk factors in its development?

Pathophysiology of Osteoarthritis

 As mentioned in the introductory section, the main tissue affected in this disease is the cartilage.  So let us take a little time to explore in greater detail what cartilage exactly is.

The main cell type found in cartilage is the chondrocyte.   These cells come from precursor cells called chondroblasts, which get trapped within the developing cartilage in spaces called lacunae.  From this site they function to produce all the constituents, such as collagen (designated as type 2), that gives cartilage its functional characteristics.  A disadvantage of having the chondrocytes located within these lacunae is that they are unable to migrate to areas of damage. The effect of this is that, consequently, cartilage has a poor propensity to heal.  This is further compromised by the presence of the cartilage matrix, which acts as a barrier to immune cells, such as lymphocytes and immunoglobulins, which may assist in the healing process. Similarly, the lack of a blood supply to the cartilage means that new matrix formation is slow, limiting its ability to recover from insult.

So in effect, whilst cartilage has a very unique structure that provides it with useful functional characteristics, it is at the expense of being able to recover from injury.  It is this injury which progresses over time to become osteoarthritis, causing the typical symptoms of the disease, including pain, deformity, and ultimately loss of function.

What are the factors that lead to abnormal chondrocyte function, which in effect leads to Osteoarthritis?  In fact there are a number, but in essence these all relate to two factors that interact to incite the onset of the disease as well as contribute to its progression.  These two factors are your genetics and the presence of abnormal biomechanics that place undue stresses on the joint (and hence cartilage).  Before considering these factors in turn, let us pause to consider what happens to the cartilage in Osteoarthritis.

It is believed that the initial abnormality that signals the onset of Osteoarthritis is the malfunction of the chondrocyte.  As a consequence of this malfunction the composition of the cartilage changes.  The production of the large proteins that retain water within the cartilage is reduced and so overtime the cartilage becomes dehydrated.   Think of this in a similar way as you would an old dry sponge or even your skin.  That is, it becomes more brittle.  In that state, when a load is applied the structure is more likely to fail, and cracks begin to appear.  This cracking in the cartilage is termed fissuring.  Overtime as more cracks begin to develop then pieces of the cartilage flake away, with no new cartilage produced to fill in the gaps.  The loss of cartilage can be inferred from x-rays that show a narrowing of the joint space between the bones.  In the end, there is no cartilage left to cover the bone and hence any movement of the joint requires bone to move directly against bone.  This is why your health care professional would say to you that once the damage of Osteoarthritis has occurred then it is not reversible/curable.

Now, in the early stages of the disease the bone attempts to do all that it can and, in fact, the body lays down more bone around the joint to strengthen the region.  This extra bone formation is often seen on x-rays, which proceed on to form what are called osteophytes.  However, bone was never developed to be able to withstand such an insult as dealing with the repetitive load of joint movement and as such it fatigues.  The result of this failure is pain.  The bone adjacent to the joint develops micro-fractures that cause swelling, stimulating the abundant nerve endings that signal pain to the brain.  Recently, it has been demonstrated that even other structures in the joint can become swollen in the disease (such as the lining of the joint), which also contributes to the sufferers’ symptoms.  It is at this point often that joint deformity begins to develop, ultimately leading to a loss of function and hence capacity to perform your desired activities.

So returning to the initial event, what causes the chondrocyte to stop functioning?  That is the million-dollar question!!  Solving that dilemma could potentially prevent the disease from progressing.  Consequently, answering that question is the current focus of numerous research groups, since the discoverer would surely be rewarded with a pretty penny!  An advance in our understanding of cartilage biology, as a result of the research thus far undertaken, has definitely progressed.  We now have a clearer insight into the important role played by genetics in regards to chondrocyte function, especially with certain manifestations of the disease.  For example, Osteoarthritis that develops in the hands and at the base of the thumbs relates to ones genetics more so than involvement of the knees.   In that example it seems that maternal inheritance is most important.

However, genetics is only part of the story.   The other important factors affecting chondrocyte function relate to the loading of the joint.  This may be in the form of a traumatic event, the distribution of forces across a joint (called biomechanics), and simply to the overall forces bearing upon a joint relating to the patient’s weight.  With reference to the first point, a traumatic event such as a fracture involving the joint or to a ligamentous injury resulting in instability at the joint has for some time been known to result in the development of Osteoarthritis.  This seems to be independent of whether the fracture heals successfully or the ligament is surgically repaired to re-establish stability.

The typical example of this is a rupture of the Anterior Cruciate ligament of the knee.  This ligament plays a very important role in stability of the knee.  It is commonly injured in those who participate in sports that demand the athlete to rapidly change direction whilst running, such as occurs with football, rugby, and netball.  The affected athlete often proceeds to surgical repair in order to regain stability in the knee to allow them to return to their sport.  However despite this, the incidence of Osteoarthritis at the affected joint is nevertheless increased.  The conclusion from this observation is that the injury is an inciting event that commences a cascade of changes in the function of the chondrocyte that ultimately leads to its failure and the subsequent development of Osteoarthritis.

Biomechanics refers to the forces that act upon a structure, and in Osteoarthritis, that means the joint.  There are a number of factors that determine the biomechanics of a joint, including the structure of the joint as well as the effect of surrounding structures such as muscles, tendons, and the joints above and below.  In the lower limb (aka; legs) the children’s song that highlights the foot bone is connected to the knee bone is very appropriate in that what is occurring at (for example) the foot and ankle affects the situation at the knee.  We will discuss this in more detail when we consider the approach to treatment.  However, although we generally consider biomechanics in Osteoarthritis in a purely mechanical way, the fact is that genetics in this regard also plays an important role.

That is, your genetics will determine the structure/shape of your bones (and joints) such that if there is any abnormality the joint will be more predisposed to disease.  The classical example of this occurs at the hip joint where, most recently, the shape at the end of the thigh bone (called the femoral neck) as well as the shape of the pelvic cup in which the thigh bone sits (called the acetabulum) have been identified as the most important predictors regarding the development of Osteoarthritis in that joint.  This occurs because these abnormal shapes result in abutment of the two bones during movement, in what has come to be known as femoroacetabular impingement.

Finally and no way in the least, the general load placed upon a joint is particularly important.  In this, I mean, the weight of the individual being carried by the joint.  This explains the observation that obese individuals are more likely to developed osteoarthritis at the knees than those who are of normal weight.  It has been shown that the progression of arthritis at the knee joint is more rapid in those who are overweight and there is conversely a slowing of the disease with even a modest reduction of weight, since for every kilogram lost there is 4kg less load exerted through the knee joint with every step6.   We will expand on the value of weight loss in more detail when we discuss the management of Osteoarthritis.

Therefore, by the completion of this section I hope you have gained a greater understanding of what Osteoarthritis means and the factors that contribute to its onset and progression.  In future though, I predict that to the factors described above I will be adding metabolic conditions.  There already exists some evidence that metabolic diseases, such as diabetes, results in a higher risk of developing Osteoarthritis independent of the individual’s weight.  Although further research into this area is needed, the insights gained into this factor may promise possible opportunities to intervene, which may lessen the risk of develop the disease or delay its progression.

In the next section we will review the approach to diagnosing the disease and thereafter to how the condition can be managed.


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