What is the most common cause of knee pain?

The most common cause of pain in the knees is damaged cartilage and thickening of the bone around the cartilage. This disease is called osteoarthritis. The old-fashioned name of this disease is arthrosis. The pain is often accompanied by the feeling of stiffness, especially  during the first movements after inactivity. Sometimes the knees may also crackle (squeak) audibly. The pain as a result of osteoarthritis is present in around 10 out of 100 men and in 13 out of 100 women above 60 years of age. With ageing, more and more people are affected by such discomfort. The signs of joint thickening are observed by examination, while rarely and temporarily the signs of joint inflammation may also be seen.

We distinguish between two primary joint diseases, joint inflammation (arthritis) and a degenerative joint disease (osteoarthritis or arthrosis). The signs of inflammation of a joint are a swelling, pain in the joint which intensifies during inactivity, joint temperature higher than normal, and sometimes redness of skin in the joint area. With osteoarthritis, there are most often no typical indications of inflammation. In osteoarthritis (arthrosis), the joint mostly hurts when being used, while during inactivity the pain subsides, there is no high temperature nor redness above the joint and rarely and transiently the knee may swell or there may be excess liquid in the joint. Even back in the old times, while observing the joints in this disease, doctors noticed that there were no clear signs of the inflammation of joints, but that the joint was painful, suffered damage and degenerated. It was for this reason that this disease was termed a degenerative joint disease, as derived from degeneration (decay, destruction, deterioration, damage, etc.), and they named the disease arthrosis. The name arthrosis served to make a clear distinction of this disease from the joint disease called arthritis, which displays clear signs of inflammation (swelling, joint pain which increases during inactivity, joint temperature higher than normal and sometimes redness of skin in the joint area). Since new studies have shown that inflammation is also present in arthrosis, but that it much less noticeable than in arthritis and thus cannot be observed by an ordinary examination, doctors have decided to use the term osteoarthritis instead of arthrosis. Nowadays both terms are often used to denote this disease (arthrosis, i.e. osteoarthritis), while it is emphasised that degenerative changes (damage, deterioration) are in question.


When do degenerative changes in the osteoarticular system start, what accelerates them and what impedes their progress?

Degenerative changes in the joint most frequently begin in middle age and they develop slowly. People usually do not feel any discomfort over years and even decades or they feel mild transient pain or crackling in their joints.  Most often they do not worry about  their temporary discomfort, they attribute them to overusing their joints, they believe the joints will recover completely and they do not consult a doctor. In the fifties and especially in the sixties and later,  the signs of osteoarthritis (most frequently pain and crackling or squeaking in the joints) start to appear more often. Occasionally, with excessive burdening of knees (long walks or unusual overuse through work or carrying load), knees may swell and start to be very painful. It is then that people address a doctor and an experienced doctor can recognise that a temporary inflammation in knee osteoarthritis (arthrosis) is in question.

Osteoarthritis may develop rapidly with persons who have previously suffered a knee injury (sports injuries, work injuries, excessive use of the joint, road traffic injuries, etc. ), with persons who have arthritis which affects the knees (rheumatoid arthritis, psoriatic arthritis, gout and other types of arthritis). More rapid development of osteoarthritis is also observed in persons who are overweight (body mass index over 25), whose blood relatives (mother, father, grandmothers, grandfathers, sisters, brothers) have osteoarthritis or whose knee joints are placed under a large amount of stress as a result of irregularities (so called knock knees or bow legs). What can contribute to more rapid development of osteoarthritis are various other diseases (severe metabolic disorders, diabetes, thyroid diseases, excessive mobility of the joints, etc.) as well as bad habits (smoking accelerates the development of osteoarthritis). Insufficient physical activity and weak muscles may also contribute to the development of osteoarthritis.


How can knee osteoarthritis be detected early?

The problems which are the sign of osteoarthritis are pain in one or both knees which is not linked to an injury, pain which intensifies with the burdening of the knee (carrying load, ascending or descending the stairs, pain felt during a sporting activity, etc.) and which is accompanied by short-term morning stiffness in the knee, which disappears after the several first movements or after a few minutes.

In case you experience such discomfort, you should  consult a doctor who specializes in joint diseases (a rheumatologist, a physiatrist, an orthopaediatrician, etc) and the doctor should check whether osteoarthritis is present. What is the most important for a doctor is to inquire carefully whether you have typical symptoms and signs of osteoarthritis, to examine you and assess how you walk and then to examine you additionally, if required.  One of the very useful additional examinations is the ultrasound examination of the joints as it may reveal the initial signs which indicate knee osteoarthritis. When these signs are linked to typical complaints and the  results of the examination, it may significantly contribute to the early diagnosis of osteoarthritis. X-ray (RTG) imaging detects the typical signs of osteoarthritis late, in the advance stage of the disease, and thus it is not useful for early diagnosing. A doctor may sometimes order magnetic resonance imaging (MRI) or a computed tomography (CT) scan , when it can be useful for the confirmation of the diagnosis, assessment of the condition or a check whether there might be some other diseases present which are the cause of complaints. Laboratory tests are of no particular use as there are no typical laboratory test results which would indicate that osteoarthritis is in question. Blood tests may be ordered when the clinical picture is not clear and when it is necessary to check  whether another disease may be the cause of discomfort (rheumatoid arthritis, gout, etc.).


How can osteoarthritis be prevented or at least its progress be impeded?

One of the best known ways of preventing the early development of hip osteoarthritis is that parents take their babies to have their hips examined using ultrasound as well as to diaper their babier widely so that the hips would develop healthily. It is of utmost importance. In order to prevent the osteoarthritis of the joints, especially knees and hips, it is necessary that the whole of society be engaged and not only the health care system and aware individuals. Each of us should know what is important for healthy joints in general and thus for prevention or, at least, impeding the progress of osteoarthritis. It is crucial that we are moderately physically active on a daily basis and that we walk sufficiently (we should walk for at least an hour a day and walking for two hours a day is desirable). It is important that we have strong muscles and that we are not overweight. All irregularities in the development of the peripheral joints and the spine have to be corrected as early as in early childhood and the doctors should be consulted thereof.  The efforts of the whole of society that people should have adequate conditions and that they comport themselves adequately at their workplace, at home and in traffic are of particular importance.  Injuries at home, in traffic and at workplace contribute significantly to the rapid development of  osteoarthritis of the joints which have previously suffered an injury or were immobilised (in cast) for bone and surrounding tissue injuries.


How can knee osteoarthritis be treated?

Before talking about the treatment of knee osteoarthritis, I would like to point to three basic rules which 38 years of learning about and experience in treating this disease have taught me:

  • When there are several dozens of drugs and treatment methods for a disease (knee osteoarthritis, in this particular case) you should know that none of them resolves the problem quickly or easily (as there would be one such drug or treatment method only).
  • Do not treat yourself on your own, without advice given by a doctor who is an expert in treating osteoarthritis as it is highly likely that you will make a mistake, waste valuable time and that your disease will worsen.
  • Be patient, persistent and ready to change your habits and lifestyle which have contributed to the constant deterioration of your disease (insufficient physical activity, overweight, etc.) as there is no such doctor who will help you if you are not ready to help yourself and your doctor by changing unhealthy habits.


We treat osteoarthritis using the following methods:

  • General measures
  • Drugs
  • Physical therapy
  • Surgical treatment


General measures for osteoarthritis treatment

The treatment of osteoarthritis, as a rule, involves the change of behaviour and lifestyle if bad habits, obesity or other problems are significant in the onset of osteoarthritis. Excess weight should be reduced, muscles should be strengthened and healthy habits as regards diet and physical activity (especially walking) should be adopted gradually. That will contribute to lower stress on the joints and their recovery. Walking is very important as mild impact stress on the cartilage during walking contributes to their recovery and proper regeneration. Moreover, regular physical exercise is also recommendable (there are data indicating that Thai chi and yoga exercises are beneficial). A doctor should be consulted when planning these activities. It is good to give up smoking. Sometimes it is necessary that the knee be secured with an orthosis or that a cane be used, which has to be done upon advice from and under the supervision of a doctor. I would like to highlight that the mentioned steps are extremely important and most difficult to implement. Unfortunately, people are rarely ready to change their life habits. They most often expect that there is a pill or an injection which will repair their joints simply and forever so that they can continue with their healthy lifestyle. Such “magical” pills, injections or other treatment methods which would solve the problem quickly and easily unfortunately do not exist. The change of bad habits and unhealthy behaviour, walking, exercise and other general measures mentioned above are an inevitable part of successful treatment.


Drugs for osteoarthritis treatment

As I already mentioned in my “three basic rules” at the beginning of the article on treatment, there are several dozens of various drugs and treatment methods which are used in the treatment of knee osteoarthritis. We can divide them into those which are applied locally or rubbed on the skin and those which are taken orally and those that are administered as injections, most often as injections administered directly into the joint. For majority of them there are no reliable data on how much they help and how much they do the opposite.  Physical therapy, especially exercise, as well as surgical treatment are important treatment methods. Surgical implantation of artificial knee joints or hips is sometimes that only real solution with severe and unrepairable damage to these joints. I will briefly list only the most commonly used medications and methods as it is impossible to cover them all in this text which is intended for your readers and not for doctors.


The most common traditional “home remedies” (cabbage leaves wrapping, a compress soaked in brandy placed on the swollen joint, application of comfrey preparations and other treatment methods)

Some folk experience has shown that, for example, a cabbage leave wrapped around the joint or a compress soaked in brandy as well as other preparations and balms help the joint swelling subside. In most of the cases, the knee swelling arises as a result of overuse or minor injuries and it subsides if saved from stress for several hours or days, without any other interventions required.  There is no reliable proof that a cabbage leaf, a compress soaked in brandy or any other type of balm helped decidedly with those mild problems which an organism can fight on its own in several hours or days. If you apply these methods, be careful not to harm yourself. Wrapping nylon compresses around joints prevents the evaporation of sweat and may cause damage to the skin, alcohol (brandy) pads may damage skin severely and cause inflammation and wounds on the skin.  There are no data for many “home” balms as to whether and how much they are harmful, but it is known that they cannot cure osteoarthritis of the knee or other joints.


Non-steroidal anti-inflammatory drugs (NSAIDs)

Rubbing locally a gel or a cream which contains some of the non-steroidal anti-inflammatory drugs (NSAIDs), which are popularly known as non-steroidal anti-rheumatic drugs, is recommended as a method for pain relief and reduction of inflammation with the patients  with the initial mild form of knee osteoarthritis. Non-steroidal anti-inflammatory drugs (NSAIDs) in the form of pills or capsules are recommended as drugs which may help with pain relief and inflammatory reaction in persons with mild or moderate knee osteoarthritis. Nowadays these drugs are given preference in comparison to all other painkillers which may be taken as pills or capsules. NSAIDs are on average considered to be a better choice in comparison to therapy using paracetamol and in comparison to therapy using opioid analgesics. When choosing a certain NSAID, one should take care of the patient’s age, and whether he or she are prone to  gastrointestinal bleeding or whether he or she suffers from a heart and/or vascular disease. Care should also be taken of kidney, lung and liver diseases as well as of the diseases of other organs.  It is believed that moderately COX2 selective NSAIDs are more suitable for the application with persons with a higher risk from gastrointestinal bleeding. It should also be known that NSAIDs may not significantly help in the recovery of the cartilage and it is the main problem in osteoarthritis.



Paracetamol may be used conditionally and occasionally in routine treatment of knee osteoarthritis if the patient may not take NSAIDs.  Research has shown that paracetamol is in most cases not sufficiently effective or is ineffective at pain relief. When using paracetamol in treatments, one should take care that it may damage the liver and the daily dosage administered should not exceed 3 grams, divided into several doses.


Antidepressants, anxiolytics

There are few good quality data on the relation between the benefits and the potential side effects in the application of antidepressants and anxiolytics in knee osteoarthritis treatment. Nonetheless, the Osteoarthritis Research Society International (OARSI) conditionally recommended the application of duloxetine and other drugs belonging to this group with patients who suffer from intense pain and/or depression in its recommendations published in 2019. It should be carefully assessed whether their application is necessary and the doctor should explain to the patient what the potential benefits and what the potential problems are in therapy involving the use of these drugs.


Tramadol and other opioid medicines

Tramadol and other opioid medicines are not recommended as routine drugs in treating pain in osteoarthritis as there are not enough data on the favourable relation between the benefits and potential side effects. They may be occasionally administered when patients may not take NSAIDs. In those cases, they should be used very cautiously, for a short period of time and with the careful assessment of potential side effect. Special caution is required for potential addiction to some of the opioid medicines.


Glucosamine sulphate

Glukosamine is an ingredient in numerous food supplements which are advertised as being helpful in treating osteoarthritis, and one preparation, namely glucosamine sulphate, is also registered as a drug. There are data from numerous studies that glucosamine does not help with osteoarthritis, but there is some research which confirmed that  glucosamine may relieve pain and improve the function of joints in osteoarthritis. For the time being, the American College of Rheumatology (the association of the rheumatologists of the USA) does not officially recommend taking glucosamine in treating osteoarthritis as there are no reliable data on the successful treatment with glucosamine.


Chondroitin sulphate and the combination of glucosamine and chondroitin sulphate

For the time being, there is no reliable proof that chondroitin sulphate as well as combinations of glucosamine sulphate and chondroitin sulphate help in treating osteoarthritis of the knee or osteoarthritis of the hip. There is research which has shown that chondroitin sulphate reduces pain, while not being harmful with osteoarthritis of the hand joints. New reliable proof is required so that more would be known about the effect of these preparations.


Vitamin D and fish oil  

Vitamin D and fish oil may be beneficial food supplements, but so far rare research have failed to prove that they are useful for treating osteoarthritis.


– Which drugs and preparations may be injected into no to improve their mobility and reduce pain?


Glucocorticoids injected into joints

Glucocorticoids are drugs which have powerful anti-inflammatory effect. Glucocorticoids injected into joints are recommended for treating knee osteoarthritis when there is a prominent inflammatory reaction and when there is swelling and excess liquid in the knee (popularly called water in the knee). These glucocorticoid injections may be of short-term assistance in reducing inflammation, swelling and knee pain. It is suspected that too frequent administration of these injections may accelerate damage to the cartilage and thus worsen osteoarthritis. Although there is no conclusive proof for such claims, the administration of glucocorticoid injection should still be restricted to situations where there is severe inflammatory reaction in the knee and if the inflammation is to be reduced promptly. It is recommended that these injections should be given with ultrasound control. Ultrasound examination of the joint may precisely investigate  the condition of the joint and confirm whether there is inflammation, excess liquid and the need for administering a glucocorticoid injection. Moreover, ultrasound examination may precisely guide the injection needle to the intended target (joint space), lead to extracting excess liquid from the joint  and show and confirm that the medication entered the right place.


Hyaluronate (sodium hyaluronate) injected into joints

Hyaluronate injections have been used in treating osteoarthritis for several centuries. Numerous clinical studies have shown that there are benefits from such treatment. The Osteoarthritis Research Society International (OARSI) recommended the application of hyaluronate injections in treating knee osteoarthritis in its recommendations published in 2019, as their analysis showed that the favourable effect of these injections lasts longer than the effect of glucocorticoid injections and that they are safer for long-term treatment. Conversely, the group of experts of the American College of Rheumatology (the association of the rheumatologists of the USA) was more critical of these drugs in its latest manual for treating osteoarthritis dating from 2020. They asserted that the majority of studies which had confirmed the benefits from treatment using hyaluronate had had the tendency for error in their assessment. Their more recent analysis of results, which included only clinical tests in which the tendency for error (the possibility of falsely positive results) was minimal, had shown that hyaluronate was not significantly better than a simple saline solution (saline solution is a small quantity of salt dissolved in water, of the same concentration is in the human body). However, they stated in their recommendations that  hyaluronate injections may be used when preceding treatment methods (exercise, loss of excess weight, NSAID pills, glucocorticoid injections, etc.) were not effective.


– What effect does treatment using processed blood which is also injected into the knee have?


Platelet-rich plasma – PRP

Platelet-rich plasma which is injected into the knee joint is a method in treating osteoarthritis which has been used for years. However, the Osteoarthritis Research Society International (OARSI) declared against the application of this method in its recommendations published in 2019, as the existing published results were of poor quality and thus it could not be concluded with certainty how useful this method really was. They recommended that the results of future better quality tests should be awaited. Like OARSI, the group of experts of the American College of Rheumatology (the association of the rheumatologists of the USA) opposed to the application of this method in its most recent manual for treating osteoarthritis dating from 2020, because it was worried about the diversity and lack of standardisation of PRP preparations which were used. Despite this rather cautious opinion of the world experts, a lot of doctors who treat osteoarthritis use this method, relying on their own good experience in the application of this treatment.


Stem cells injected into the knee joint

Stem cells from bone marrow or from adipose tissue or from peripheral blood are used in the treatment of knee osteoarthritis. The idea behind the application of this method is that stem cells might develop into new cells of the cartilage and help in the recovery of this tissue or that they would secrete molecules which would recover the cartilage in osteoarthritis, but the details of their effectiveness are still unknown.  Currently, there are few good quality studies published on the topic of the transplantation of stem cells with the aim of cartilage recovery, although their effectiveness in the prevention and treatment of experimental osteoarthritis has been proved with  experimental animals. The Osteoarthritis Research Society International (OARSI) as well as the American College of Rheumatology (the association of the rheumatologists of the USA) declared against the application of stem cells in the treatment of knee osteoarthritis (for the time being, they do not recommend their application) in their recommendations published in  2019 and in their most recent manual for treating osteoarthritis dating from 2020 respectively, as the results originating from the research were of insufficient quality and the applied methods were different, which made the comparison of results difficult.


Orthokine (autologous conditioned serum)

Orthokine is the treatment with molecules which are produced by the blood cells of the very patient, which reduce inflammation and stimulate the recovery of damaged and diseased tissue of the patient. Forty millilitres of the patient’s blood is extracted into special syringes which contain pecially prepared sterile glass beads. Certain blood cells attach to the surface of these beads during six-hour incubation at the temperature of  37°C. Such connection induces the activation of these cells which produce and secrete molecules (cytokines and growth factors) into plasma which reduce inflammation and stimulate the regeneration of damaged and diseased tissue. Following 6-hour incubation, the blood is centrifuged, and the serum which does not contain cells and is enriched with anti-inflammatory cytokines and growth factors is isolated. The serum is injected into the knee joint. There are data according to which this method has longer-term effects in the regeneration of the knee joint in comparison to treatment using glucocorticoids    and hyaluronate, with reasonable safety. Additional research is required so that we would have  even better insight into the effectiveness of this method.


Other drugs for which there is insufficient proof that they are effective in treating osteoarthritis (arthrosis) of the knee

Prolotherapy, injecting botulinum toxin into joints


Other drugs which are not recommended for the treatment of osteoarthritis of the knee

Hydroxychloroquine, methotrexate, Tumor Necrosis Factor Inhibitors (TNFi), s interleukin-1 receptor antagonist (IL1-Ra).


– Which of these drugs and preparations are available on doctor’s prescription? What gives the best results?

I suppose that the patient has to pay himself for the majority of them?

Unfortunately, drugs which are recommended for treating osteoarthritis are not available upon doctor’s prescription at the expense of the Republic Fund of Health Insurance for this disease. Patients have to buy them themselves.


Physical therapy

Certain methods used in physical therapy may help in the recovery of the patient  suffering from osteoarthritis of the knee. Physical exercise stands out among them. When physical exercise is properly planned for individual patients, it may help significantly.


Surgical treatment

In the case of a severely damaged knee, when drug treatment and physical therapy cannot help,  surgical treatment, especially implantation of an artificial knee, may help significantly and may improve the quality of the patient’s life considerably. This method is expensive. Surgeries are performed routinely in orthopaedic centres in Serbia and the rate of success is extremely high. However, it should be taken into consideration that very rarely serious complications are possible as well as that prostheses have their shelf life.


Conclusion: Everyday moderate physical activity, and strong muscles, without excess adipose tissue, contribute to correct use of joints and slow down the development of osteoarthritis. Adequate conditions and proper behaviour at workplace, at home and in traffic reduce the risk from injuries and thus reduce the later rapid development of osteoarthritis as a result of an injury. There is no drug or treatment method which may quickly and easily cure a joint affected by osteoarthritis. Only doctors engaged in treatment of osteoarthritis may properly select drugs and other treatment methods which will help a certain patient the most.


Written by Prof. Nemanja Damjanov, MD, PhD

Source: novosti.rs