Supriya Ghosh (Editor)

Osteoarthritis

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Covid-19
ICD-10  M15-M19, M47
OMIM  165720
ICD-9-CM  715
DiseasesDB  9313
Osteoarthritis
Synonyms  degenerative arthritis, degenerative joint disease, osteoarthrosis
Specialty  Rheumatology, orthopedics

Osteoarthritis (OA) is a type of joint disease that results from breakdown of joint cartilage and underlying bone. The most common symptoms are joint pain and stiffness. Initially, symptoms may occur only following exercise, but over time may become constant. Other symptoms may include joint swelling, decreased range of motion, and when the back is affected weakness or numbness of the arms and legs. The most commonly involved joints are those near the ends of the fingers, at the base of the thumb, neck, lower back, knee, and hips. Joints on one side of the body are often more affected than those on the other. Usually the symptoms come on over years. It can affect work and normal daily activities. Unlike other types of arthritis, only the joints are typically affected.

Contents

Causes include previous joint injury, abnormal joint or limb development, and inherited factors. Risk is greater in those who are overweight, have one leg of a different length, and have jobs that result in high levels of joint stress. Osteoarthritis is believed to be caused by mechanical stress on the joint and low grade inflammatory processes. It develops as cartilage is lost and the underlying bone becomes affected. As pain may make it difficult to exercise, muscle loss may occur. Diagnosis is typically based on signs and symptoms, with medical imaging and other tests occasionally used to either support or rule out other problems. In contrast to rheumatoid arthritis, which is primarily an inflammatory condition, in osteoarthritis, the joints do not typically become hot or red.

Treatment includes exercise, efforts to decrease joint stress, support groups, and pain medications. Efforts to decrease joint stress include resting and the use of a cane. Weight loss may help in those who are overweight. Pain medications may include paracetamol (acetaminophen) as well as NSAIDs such as naproxen or ibuprofen. Long-term opioid use is generally discouraged due to lack of information on benefits as well as risks of addiction and other side effects. If pain interferes with normal life despite other treatments, joint replacement surgery may help. An artificial joint typically lasts 10 to 15 years.

Osteoarthritis is the most common form of arthritis with disease of the knee and hip affecting about 3.8% of people as of 2010. Among those over 60 years old, about 10% of males and 18% of females are affected. It is the cause of about 2% of years lived with disability. In Australia, about 1.9 million people are affected, and in the United States, 30 to 52.5 million people are affected. It becomes more common in both sexes as people become older.

Signs and symptoms

The main symptom is pain, causing loss of ability and often stiffness. "Pain" is generally described as a sharp ache or a burning sensation in the associated muscles and tendons, and is typically made worse by prolonged activity and relieved by rest. Stiffness is most common in the morning, and typically lasts less than thirty minutes after beginning daily activities, but may return after periods of inactivity. Osteoarthritis can cause a crackling noise (called "crepitus") when the affected joint is moved or touched and people may experience muscle spasms and contractions in the tendons. Occasionally, the joints may also be filled with fluid. Some people report increased pain associated with cold temperature, high humidity, and/or a drop in barometric pressure, but studies have had mixed results.

Osteoarthritis commonly affects the hands, feet, spine, and the large weight-bearing joints, such as the hips and knees, although in theory, any joint in the body can be affected. As osteoarthritis progresses, the affected joints appear larger, are stiff, painful and may swell, but usually feel better with gentle use but worse with excessive or prolonged use, thus distinguishing it from rheumatoid arthritis.

In smaller joints, such as at the fingers, hard bony enlargements, called Heberden's nodes (on the distal interphalangeal joints) and/or Bouchard's nodes (on the proximal interphalangeal joints), may form, and though they are not necessarily painful, they do limit the movement of the fingers significantly. Osteoarthritis at the toes leads to the formation of bunions, rendering them red or swollen. Some people notice these physical changes before they experience any pain, in part because the cartilage damage in osteoarthritis is generally painless because cartilage is aneural.

Osteoarthritis is the most common cause of a joint effusion of the knee.

Risk factors

Damage from mechanical stress with insufficient self repair by joints is believed to be the primary cause of osteoarthritis. Sources of this stress may include misalignments of bones caused by congenital or pathogenic causes; mechanical injury; excess body weight; loss of strength in the muscles supporting a joint; and impairment of peripheral nerves, leading to sudden or uncoordinated movements. However exercise, including running in the absence of injury, has not been found to increase the risk. Nor has cracking one's knuckles been found to play a role.

Primary

A number of studies have shown that there is a greater prevalence of the disease among siblings and especially identical twins, indicating a hereditary basis. Although a single factor is not generally sufficient to cause the disease, about half of the variation in susceptibility has been assigned to genetic factors.

As early human ancestors evolved into bipeds, changes occurred in the pelvis, hip joint and spine which increased the risk of osteoarthritis. Additionally genetic variations that increase the risk were likely not selected against because usually problems only occur after reproductive success.

The development of osteoarthritis is correlated with a history of previous joint injury and with obesity, especially with respect to knees. Since the correlation with obesity has been observed not only for knees but also for non-weight bearing joints and the loss of body fat is more closely related to symptom relief than the loss of body weight, it has been suggested that there may be a metabolic link to body fat as opposed to just mechanical loading.

Changes in sex hormone levels may play a role in the development of osteoarthritis as it is more prevalent among post-menopausal women than among men of the same age. A study of mice found natural female hormones to be protective while injections of the male hormone dihydrotestosterone reduced protection.

Secondary

This type of osteoarthritis is caused by other factors but the resulting pathology is the same as for primary osteoarthritis:

  • Alkaptonuria
  • Congenital disorders of joints
  • Diabetes doubles the risk of having a joint replacement due to osteoarthritis and people with diabetes have joint replacements at a younger age than those without diabetes.
  • Ehlers-Danlos Syndrome
  • Hemochromatosis and Wilson's disease
  • Inflammatory diseases (such as Perthes' disease), (Lyme disease), and all chronic forms of arthritis (e.g., costochondritis, gout, and rheumatoid arthritis). In gout, uric acid crystals cause the cartilage to degenerate at a faster pace.
  • Injury to joints or ligaments (such as the ACL), as a result of an accident or orthopedic operations.
  • Ligamentous deterioration or instability may be a factor.
  • Marfan syndrome
  • Obesity
  • Joint infection
  • Pathophysiology

    While osteoarthritis is a degenerative joint disease that may cause gross cartilage loss and morphological damage to other joint tissues, more subtle biochemical changes occur in the earliest stages of osteoarthritis progression. The water content of healthy cartilage is finely balanced by compressive force driving water out and hydrostatic and osmotic pressure drawing water in. Collagen fibres exert the compressive force, whereas the Gibbs–Donnan effect and cartilage proteoglycans create osmotic pressure which tends to draw water in.

    However, during onset of osteoarthritis, the collagen matrix becomes more disorganized and there is a decrease in proteoglycan content within cartilage. The breakdown of collagen fibers results in a net increase in water content. This increase occurs because whilst there is an overall loss of proteoglycans (and thus a decreased osmotic pull), it is outweighed by a loss of collagen. Without the protective effects of the proteoglycans, the collagen fibers of the cartilage can become susceptible to degradation and thus exacerbate the degeneration. Inflammation of the synovium (joint cavity lining) and the surrounding joint capsule can also occur, though often mild (compared to the synovial inflammation that occurs in rheumatoid arthritis). This can happen as breakdown products from the cartilage are released into the synovial space, and the cells lining the joint attempt to remove them.

    Other structures within the joint can also be affected. The ligaments within the joint become thickened and fibrotic and the menisci can become damaged and wear away. Menisci can be completely absent by the time a person undergoes a joint replacement. New bone outgrowths, called "spurs" or osteophytes, can form on the margins of the joints, possibly in an attempt to improve the congruence of the articular cartilage surfaces in the absence of the menisci. The subchondral bone volume increases and becomes less mineralized (hypomineralization). All these changes can cause problems functioning. The pain in an osteoarthritic joint has been related to thickened synovium and subchondral bone lesions.

    Diagnosis

    Diagnosis is made with reasonable certainty based on history and clinical examination. X-rays may confirm the diagnosis. The typical changes seen on X-ray include: joint space narrowing, subchondral sclerosis (increased bone formation around the joint), subchondral cyst formation, and osteophytes. Plain films may not correlate with the findings on physical examination or with the degree of pain. Usually other imaging techniques are not necessary to clinically diagnose osteoarthritis.

    In 1990, the American College of Rheumatology, using data from a multi-center study, developed a set of criteria for the diagnosis of hand osteoarthritis based on hard tissue enlargement and swelling of certain joints. These criteria were found to be 92% sensitive and 98% specific for hand osteoarthritis versus other entities such as rheumatoid arthritis and spondyloarthropathies.

    Related pathologies whose names may be confused with osteoarthritis include pseudo-arthrosis. This is derived from the Greek roots pseudo-, meaning "false", and arthr-, meaning "joint", together with the ending -osis used for disorders. Radiographic diagnosis results in diagnosis of a fracture within a joint, which is not to be confused with osteoarthritis which is a degenerative pathology affecting a high incidence of distal phalangeal joints of female patients. A polished ivory-like appearance may also develop on the bones of the affected joints, reflecting a change called eburnation.

    Classification

    A number of classification systems are used for gradation of osteoarthritis:

  • WOMAC scale, taking into account pain, stiffness and functional limitation.
  • Kellgren-Lawrence grading scale for osteoarthritis of the knee. It uses only projectional radiography features.
  • Tönnis classification for osteoarthritis of the hip joint, also using only projectional radiography features.
  • Osteoarthritis can be classified into either primary or secondary depending on whether or not there is an identifiable underlying cause.

    Both primary generalized nodal osteoarthritis and erosive osteoarthritis (EOA, also called inflammatory osteoarthritis) are sub-sets of primary osteoarthritis. EOA is a much less common, and more aggressive inflammatory form of osteoarthritis which often affects the distal interphalangeal joints of the hand and has characteristic articular erosive changes on x-ray.

    Management

    Lifestyle modification (such as weight loss and exercise) and analgesics are the mainstays of treatment. Acetaminophen (also known as paracetamol) is recommended first line with NSAIDs being used as add on therapy only if pain relief is not sufficient. This is due to the relative greater safety of acetaminophen.

    Lifestyle changes

    For overweight people, weight loss may be an important factor. Patient education has been shown to be helpful in the self-management of arthritis. It decreases pain, improves function, reduces stiffness and fatigue, and reduces medical usage. Patient education can provide on average 20% more pain relief when compared to NSAIDs alone in patients with hip osteoarthritis.

    Physical measures

    Moderate exercise is beneficial with respect to pain and function in those with osteoarthritis of the knee and hip. These exercises should occur at least three times per week. While some evidence supports certain physical therapies, evidence for a combined program is limited. There is not enough evidence to determine the effectiveness of massage therapy. The evidence for manual therapy is inconclusive. Functional, gait, and balance training have been recommended to address impairments of position sense, balance, and strength in individuals with lower extremity arthritis as these can contribute to a higher rate of falls in older individuals.

    Lateral wedge insoles and neutral insoles do not appear to be useful in osteoarthritis of the knee. Knee braces may help but their usefulness has also been disputed. For pain management heat can be used to relieve stiffness, and cold can relieve muscle spasms and pain. Among people with hip and knee osteoarthritis, exercise in water may reduce pain and disability, and increase quality of life in the short term. Also therapeutic exercise programs such as aerobics and walking reduce pain and improve physical functioning for up to 6 months after the end of the program for people with knee osteoarthritis.

    Medication

    The pain medication acetaminophen is the first line treatment for osteoarthritis. However, a 2015 review found acetaminophen to only have a small short-term benefit. For mild to moderate symptoms effectiveness is similar to non-steroidal anti-inflammatory drugs (NSAIDs), though for more severe symptoms NSAIDs may be more effective. NSAIDs such as naproxen, while more effective in severe cases, are associated with greater side effects, such as gastrointestinal bleeding. Diclofenac may be the most effective NSAID.

    Another class of NSAIDs, COX-2 selective inhibitors (such as celecoxib) are equally effective when compared to nonselective NSAIDs, and have lower rates of adverse gastrointestinal effects, but higher rates of cardiovascular disease such as myocardial infarction. They are also more expensive than non-specific NSAIDs. Benefits and risks vary in individuals and need consideration when making treatment decisions. NSAIDS applied topically are effective for a small number of people.

    Failure to achieve desired pain relief in osteoarthritis after 2 weeks should trigger reassessment of dosage and pain medication. Opioids by mouth, including both weak opioids such as tramadol and stronger opioids, are also often prescribed. Their appropriateness is uncertain, and opioids are often recommended only when first line therapies have failed or are contraindicated. This is due to their small benefit and relatively large risk of side effects. Oral steroids are not recommended in the treatment of osteoarthritis.

    There are several NSAIDs available for topical use, including diclofenac. A Cochrane review from 2016 concluded that reasonably reliable evidence is available only for use of topical diclofenac and ketoprofen in people aged over 40 years with painful knee arthritis. Transdermal opioid pain medications are not typically recommended in the treatment of osteoarthritis. The use of topical capsaicin to treat osteoarthritis is controversial, as some reviews found benefit while others did not.

    Joint injection of glucocorticoids (such as hydrocortisone) leads to short term pain relief that may last between a few weeks and a few months. Injections of hyaluronic acid have not produced improvement compared to placebo for knee arthritis, but did increase risk of further pain. In ankle osteoarthritis, evidence is unclear. The effectiveness of injections of platelet-rich plasma is unclear; there are suggestions that such injections improve function but not pain, and are associated with increased risk. A 2015 Cochrane review found that intra-articular corticosteroid injections of the knee did not benefit quality of life, had no effect on knee joint space, and clinical effects one to six weeks after injection could not be determined clearly due to poor study quality.

    Surgery

    If the impact of symptoms of osteoarthritis on quality of life is significant and more conservative management is ineffective, joint replacement surgery or resurfacing may be recommended. Evidence supports joint replacement for both knees and hips as it is both clinically effective, and cost-effective. Surgery to transfer articular cartilage from a non-weight-bearing area to the damaged area is one possible procedure that has some success, but there are problems getting the transferred cartilage to integrate well with the existing cartilage at the transfer site.

    Osteotomy may be useful in people with knee osteoarthritis, but has not been well studied. Arthroscopic surgery is largely not recommended, as it does not improve outcomes in knee osteoarthritis, and may result in harm.

    Glucosamine and chondroitin

    The effectiveness of glucosamine is controversial. Reviews have found it to be equal to or slightly better than placebo. A difference may exist between glucosamine sulfate and glucosamine hydrochloride, with glucosamine sulfate showing a benefit and glucosamine hydrochloride not. The evidence for glucosamine sulfate having an effect on osteoarthritis progression is somewhat unclear and if present likely modest. The Osteoarthritis Research Society International recommends that glucosamine be discontinued if no effect is observed after six months and the National Institute for Health and Care Excellence no longer recommends its use. Despite the difficulty in determining the efficacy of glucosamine, it remains a viable treatment option. Its use as a therapy for osteoarthritis is usually safe.

    A 2015 Cochrane review of clinical trials of chondroitin found that most were of low quality, but that there was some evidence of short-term improvement in pain and few side effects; it does not appear to improve or maintain the health of affected joints.

    Other remedies

    Avocado/soybean unsaponifiables (ASU) is an extract made from avocado oil and soybean oil that is sold under many brand names worldwide as a dietary supplement and as a drug in France. A 2014 Cochrane review found that while ASU might help relieve pain in the short term for some people with osteoarthritis, it does not appear to improve or maintain the health of affected joints; the review noted a high quality two year clinical trial comparing to ASU to chondroitin, which has uncertain efficacy in arthritis—the study found no difference between the two. The review also found that while ASU appears to be safe, it has not been adequately studied to be sure.

    Devil's claw, Curcumin, phytodolor, SKI306X and SAMe may be effective in improving pain. There is tentative evidence to support cat's claw, hyaluronan, MSM, and rose hip. A few high-quality studies of Boswellia serrata show consistent, but small, improvements in pain and function.

    There is little evidence supporting benefits for some supplements, including: the Ayurvedic herbal preparations with brand names Articulin F and Eazmov, collagen, Duhuo Jisheng Wan (a Chinese herbal preparation), fish liver oil, ginger, the herbal preparation gitadyl, omega-3 fatty acids, the brand-name product Reumalax, stinging nettle, vitamins A, C, and E in combination, vitamin E alone, vitamin K and willow bark. There is insufficient evidence to make a recommendation about the safety and efficacy of these treatments.

    Acupuncture and other interventions

    While acupuncture leads to improvements in pain relief, this improvement is small and may be of questionable importance. Waiting list-controlled trials for peripheral joint osteoarthritis do show clinically relevant benefits, but these may be due to placebo effects. Acupuncture does not seem to produce long-term benefits. While electrostimulation techniques such as TENS have been used for twenty years to treat osteoarthritis in the knee, there is no conclusive evidence to show that it reduces pain or disability.

    A Cochrane review of low level laser therapy found unclear evidence of benefit. Another review found short term pain relief for osteoarthritic knees.

    Epidemiology

    Globally as of 2010, approximately 250 million people had osteoarthritis of the knee (3.6% of the population). Hip osteoarthritis affects about 0.85% of the population.

    As of 2004, osteoarthritis globally causes moderate to severe disability in 43.4 million people. Together, knee and hip osteoarthritis had a ranking for disability globally of 11th among 291 disease conditions assessed.

    United States

    As of 2012, osteoarthritis affected 52.5 million people in the United States, approximately 50% of whom were 65 years and older. It is estimated that 80% of the population have radiographic evidence of osteoarthritis by age 65, although only 60% of those will have symptoms. The rate of osteoarthritis in the United States is forecast to be 78 million (26%) adults by 2040.

    In the United States, there were approximately 964,000 hospitalizations for osteoarthritis in 2011, a rate of 31 stays per 10,000 population. With an aggregate cost of $14.8 billion ($15,400 per stay), it was the second-most expensive condition seen in U.S. hospital stays in 2011. By payer, it was the second-most costly condition billed to Medicare and private insurance.

    History

    Evidence for osteoarthritis found in the fossil record is studied by paleopathologists, specialists in ancient disease and injury. Osteoarthritis has been reported in fossils of the large carnivorous dinosaur Allosaurus fragilis.

    Etymology

    Osteoarthritis is derived from the Greek word part osteo-, meaning "of the bone", combined with arthritis: arthr-, meaning "joint", and -itis, the meaning of which has come to be associated with inflammation. The -itis of osteoarthritis could be considered misleading as inflammation is not a conspicuous feature. Some clinicians refer to this condition as osteoarthrosis to signify the lack of inflammatory response.

    Research

    There are ongoing efforts to determine if there are agents that modify outcomes in osteoarthritis. Sprifermin is one candidate drug. There is also tentative evidence that strontium ranelate may decrease degeneration in osteoarthritis and improve outcomes.

    As well as attempting to find disease-modifying agents for osteoarthritis, there is emerging evidence that a system-based approach is necessary to find the causes of osteoarthritis. Changes may occur before clinical disease is evident due to abnormalities in biomechanics, biology and/or structure of joints that predispose them to develop clinical disease. Research is thus focusing on defining these early pre-osteoarthritis changes using biological, mechanical, and imaging markers of osteoarthritis risk, emphasising multi-disciplinary approaches, and looking into personalized interventions that can reverse osteoarthritis risk in healthy joints before the disease becomes evident.

    Gene transfer strategies aim to target the disease process rather than the symptoms.

    Biomarkers

    Guidelines outlining requirements for inclusion of soluble biomarkers in osteoarthritis clinical trials were published in 2015, but as yet, there are no validated biomarkers for osteoarthritis. A 2015 systematic review of biomarkers for osteoarthritis looking for molecules that could be used for risk assessments found 37 different biochemical markers of bone and cartilage turnover in 25 publications. The strongest evidence was for urinary C-terminal telopeptide of collagen type II (uCTX-II) as a prognostic marker for knee osteoarthritis progression and serum cartilage oligomeric protein (COMP) levels as a prognostic marker for incidence of both knee and hip osteoarthritis. A review of biomarkers in hip osteoarthritis also found associations with uCTXII.

    One problem with using a specific collagen type II biomarker from the breakdown of articular cartilage is that the amount of cartilage is reduced (worn away) over time with progression of the disease so a patient can eventually have very advanced osteoarthritis with none of this biomarker detectable in their urine. Another problem with a systemic biomarker is that a patient can have osteoarthritis in multiple joints at different stages of disease at the same time, so the biomarker source cannot be determined. Some other collagen breakdown products in the synovial fluid correlated with each other after acute injuries (a known cause of secondary osteoarthritis) but did not correlate with the severity of the injury.

    References

    Osteoarthritis Wikipedia


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