History of Osteoarthritis

The leading form of arthritis, osteoarthritis has a slow onset, progressing over years and even decades. As people are living longer, the prevalence of osteoarthritis is increasing; symptoms typically appear after age 40. Osteoarthritis affects weight-bearing joints especially the knee and hip; it rarely starts with smaller joints.

Osteoarthritis is the leading form of arthritis, contributing to significant joint pain and disability, and the number of people diagnosed with osteoarthritis is increasing. The primary reason for the rise in prevalence is that more people are living longer. People older than 65 years now outnumber those younger than 5, and this gap is expected to widen considerably. By 2030, osteoarthritis is expected to become the single greatest cause of disability globally.1 Concerningly, the prevalence of metabolic disorders is also much higher among those diagnosed with osteoarthritis.2

Despite its widespread prevalence, osteoarthritis lacks a universal disease definition. Osteoarthritis affects all the structures of the joints and is marked by cartilage degeneration and overgrowth of an underlying bony part. Clinically, osteoarthritis presents as joint pain, tenderness, limitation of movement, crepitus, infrequent effusion, and inflammation.3 This view of the disease is based on the emergence of signs and symptoms.

However, it is evident that inflammatory changes, cartilage degradation, and maladaptive repair responses typically occur well before diagnosis.3 Complicating its disease course is the lack of early, specific biomarkers for the condition and, unlike with some organs, joints may produce disability even with minor loss of function. Further, the structures of the joints have low regenerative capacity.3,4

Osteoarthritis involves certain joints that bear a higher load, and yet it spares other joints despite the high load. Strikingly, osteoarthritis of the knee is the most common form, whereas the ankle is usually spared. Other joints commonly affected include the hip, lower spine, cervical vertebrae, first carpometacarpal, first metatarsophalangeal, distal interphalangeal, and proximal interphalangeal.

Osteoarthritis represents a mechanical failure of certain joints while others, despite the mechanical stress, are more resilient. The explanation for this might lie in evolution: Humans quickly evolved from primates but inherited some weaknesses along with strengths. The explanation may account for why ankle and wrist joints are so resistant to the disease.5-7

Although no universally accepted classification of the disease exists, the traditional approach is to classify osteoarthritis as either primary (localized if occurring in 1 joint and generalized if occurring in 3 or more joints) or secondary to trauma or a metabolic disorder. Additionally, osteoarthritis may be classified based on severity as mild, moderate, or severe.8

For classifying the most common osteoarthritis of the knee, the highly sensitive Kellgren-Lawrence (KL) grading system is often used and uses radiographic observations to determine the severity of the disease. The primary criterion for diagnosis of osteoarthritis of the knee is the observation of joint space narrowing (JSN) (Table 1).9

Table 1: Radiographic grading of knee osteoarthritis
Table 1: Radiographic Grading of Knee Osteoarthritis

Epidemiology

Despite difficulties in estimating prevalence of osteoarthritis, findings show that both prevalence and incidence increased by >8% over the past 30 years. An estimated 654 million people worldwide are living with osteoarthritis. More than one-third of US adults over 60 have confirmed knee osteoarthritis, causing considerable disability in about half of cases.

There is a substantial global variance in the prevalence of osteoarthritis due to genetic and lifestyle differences. Additionally, diagnostic criteria may vary, making it difficult to estimate the full scope of prevalence.

Studies estimate that in 2017 there was an annual prevalence of 3754.2 cases of osteoarthritis per 100,000 and an incidence of 181.2 per 100,000. These findings represent increases of 9.3% in prevalence and 8.2% in incidence rate since 1990.10

The global prevalence of knee osteoarthritis is reported at 16% for individuals older than 15 years and 22.9% for those 40 years and older. Based on these data, an estimated 654 million people are living with osteoarthritis globally.11

In the United States, 10% of men and 13% of women are living with osteoarthritis. The prevalence of knee osteoarthritis increases considerably after the age of 60, causing considerable disability in half of the cases. According to the third National Health and Nutrition Examination Survey (NHANES III), 37% of individuals older than 60 years had radiographically confirmed knee osteoarthritis.12

Osteoarthritis Etiology and Risk Factors

Age is the predominant risk factor for osteoarthritis and, with people living longer than ever before, is the main reason for its increased prevalence. Women experience more severe symptoms than men and have an increased risk after menopause. Injury and mechanical factors such as knee laxity increase the risk for osteoarthritis.

A combination of factors underlies osteoarthritis, and extrinsic and intrinsic features contribute to disease development. For example, genetics, hormonal changes, sex, and age may increase the risk of disease. Obesity, joint injury, involvement in strenuous physical activity, lack of exercise, and resulting muscle weakness may also serve as triggers.4

Age

Age is the most significant risk factor for osteoarthritis and the driving force behind its rise in incidence. To illustrate its importance, a Chinese study reported the rate of knee osteoarthritis to be 3.1% in people aged 15 to 39 years and 26.3% in those older than 70 years.13 Aging is tied to various factors that influence development of osteoarthritis, including cartilage thinning, reduction in muscle strength, slowing of anabolic processes, oxidative damage, and poor proprioception. Moreover, older adults are more likely to be living with chronic disorders.

Sex

Women are more prone to osteoarthritis, and they also exhibit more severe symptoms.2,13 In addition, the incidence of osteoarthritis increases after menopause, confirming an association with hormonal changes.14 Although there is a clear association with a greater risk of osteoarthritis in postmenopausal women, the use of hormone replacement therapy for protection against osteoarthritis is controversial and the benefit seems to be of little clinical relevancy.14

Race/Ethnicity

There are considerable differences in the disease pattern of osteoarthritis among various ethnic groups. For example, the Framingham study shows that hip and hand osteoarthritis was less prevalent in Chinese individuals than in Whites; however, Chinese patients had more severe knee osteoarthritis. African American men are slightly at greater risk and prone to more severe osteoarthritis.12

Genetics

Epidemiologic studies confirm that osteoarthritis runs in families, though more research is needed to confirm a genetic link. Studies of twins show that genetic factors played a role in 39% to 65% of hand and knee osteoarthritis cases, in 60% of hip osteoarthritis cases, and in approximately 70% of spine osteoarthritis cases. In addition, studies have identified specific genes that may be associated with a higher risk of developing osteoarthritis.15

Congenital Conditions

Congenital conditions may play a relatively minor role in risk. Among these conditions, subclinical acetabular dysplasia, a mild and common abnormality, may increase the risk of osteoarthritis of the hip by as much as 3-fold.12

Diet 

Low intake of certain micronutrients is often associated with poor bone health and a greater risk of musculoskeletal disorders. Low vitamin D levels may increase the risk of osteoarthritis, and adequate intake/supplementation of vitamin D may play a role in prevention. However, the role of vitamin D in managing osteoarthritis is unclear.

Low intake of vitamin C is associated with increased disease progression, though not with a higher incidence of osteoarthritis. Selenium is suitable for bone health, but its role in osteoarthritis is uncertain, as results of studies are mixed. Vitamin K is another vital nutrient for bone health; however, it is not clear if its supplementation may help prevent osteoarthritis.12

Obesity

There is a significant association between obesity and osteoarthritis risk. The Framingham study demonstrated that weight reduction of 5% could reduce the risk of symptomatic osteoarthritis by 50% in women.12 One of the ways in which obesity increases the risk is by increasing mechanical damage to cartilage. Researchers have discovered the presence of mechanoreceptors in joint cartilage. Overload of these receptors may trigger inhibition of matrix synthesis and subsequent cartilage degradation.

Mechanical loading fails to explain the association between obesity and a higher risk of osteoarthritis of non-weight-bearing joints such as the hands. This association may be explained by increased levels of adipokines and resulting inflammation. Additionally, obesity increases the risk of atherosclerosis, influencing microcirculation. Further, obesity is associated with a greater prevalence of insulin resistance and diabetes.16

Injury

Injury is a significant factor contributing to osteoarthritis as severe injury may cause permanent changes in the joint structure. Moreover, weight-bearing joints are more prone to injuries. With regard to the knee, injuries may result in a meniscal tear or permanent damage to the ligaments.12

Sports and Occupation

Because osteoarthritis is tied in some cases to mechanical injury to the joint, sports are generally associated with an increased risk of osteoarthritis. Similarly, certain occupations may also increase risk. Participation in strenuous competitive sports such as long-distance running or soccer may increase the risk of osteoarthritis. However, in the absence of injury, recreational running and jogging are not associated with greater osteoarthritis risk.12

Mechanical

Mechanical factors, including weakened supportive muscles and ligaments, may play a role in osteoarthritis. Faulty knee alignment may result in uneven load distribution and a greater risk of osteoarthritis. Knee laxity is another risk factor as osteoarthritis is more common among those with varus or valgus deformity. Inequality of limb length may also considerably increase the risk of osteoarthritis.12

Prognosis

Factors including baseline knee pain, comorbidities, and slower walking speed may aid in progress. Research into biomarkers of disease progression is ongoing on several fronts; a prognostic biomarker has yet to be identified.

Osteoarthritis is a complex, chronic disease that progresses with time and age. However, predicting outcomes remains a challenge. Certain factors including baseline knee pain, comorbidities, psychological state, worsening of radiographic findings, and slower walking speed may help predict the course of the disease (Figure 1). Nonetheless, most systematic reviews and meta-analyses find it challenging to pool data due to heterogeneity among the studies.17-21https://e.infogram.com/254d69ce-6ed4-4c25-8e01-8e980f07fbc3?src=embed

No highly sensitive and specific biomarkers have been identified that may help predict disease progression. Researchers are exploring various biomarkers related to cartilage and bone metabolism and inflammation including urinary C-terminal telopeptide of collagen type II, serum cartilage oligomeric matrix protein, serum tumor necrosis factor-α, and serum hyaluronic acid.22,23

Osteoarthritis Diagnosis & Presentation

Osteoarthritis generally affects the joints asymmetrically. Osteoarthritis is most common in the knees, hips, and hands. Morning stiffness typically does not last more than 15 to 30 minutes. Pain is made worse by physical exertion.

Physical Examination Findings

Although any joint may be affected by osteoarthritis, the hands, knees, hips, and spine are more commonly afflicted (Table 2). In addition, osteoarthritis is asymmetrical in most cases: a person with osteoarthritis may have severe pain in the right knee and yet be pain-free in the left knee.24

Table 2: Common symptoms of Osteoarthritis
Table 2: Common Symptoms of Osteoarthritis

The AMICA study (25,589 patients evaluated), which explored the clinical presentation of osteoarthritis in general practice in Italy, found that the most common complaint was knee pain (54%), hip pain (24%), or hand pain (23%). The most common comorbidities were hypertension, obesity, osteoporosis, and diabetes. Women generally had more severe and intense pain. Symptoms also were more severe in adults older than age 70.25

Diagnostic Workup

Progression of pain in osteoarthritis

Pain is not always a reliable way of assessing the severity of osteoarthritis. Some individuals have high pain sensitivity. Thus, patients with osteoarthritis may report pain that may not show much association with the KL grade of the disease.27,28 Nonetheless, progression from mild to severe disease is identified with subjective measures of pain. 

Mild osteoarthritis – Pain may be felt occasionally, especially when doing high-impact activities or performing specific motions, such as bending at the knee or standing after sitting for a prolonged interval.

Moderate osteoarthritis – Pain occurs more frequently, lasts longer, and may occur even with mild physical exertion.

Severe osteoarthritis – Pain is a constant presence. Dull pain is felt even when resting. There may be periods of intense pain. Physical functionality is severely limited.

It is worth noting that osteoarthritis may show seasonal variation, which may be more probable in individuals prone to mood disorders such as depression. These individuals often report worsening of pain in spring and autumn.29

As the disease progresses, the severity of night pain also increases, causing sleep disorders, fatigue, and a higher risk of mental distress. Studies show that more than 80% of those living with knee or hip osteoarthritis may report night pain. Interestingly, many of the 20% without episodes of night pain have moderate to severe osteoarthritis.30

Physical examination may provide certain clues like asymmetrical deformities, swelling, and muscle wasting. Generally, the extremities of those diagnosed with osteoarthritis are colder, and there is typically joint line tenderness. Compromised range of movement is also demonstrated (Table 3).

Table 3: Telltale Signs of Osteoarthritis
Table 3: Telltale Signs of Osteoarthritis

Laboratory Testing

Laboratory testing is not required in osteoarthritis and has limited value in confirming its diagnosis; nonetheless, it may assist in the differential diagnosis. Inflammatory markers like erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) levels may be elevated, but these are not specific to the condition. In addition, assessment of antinuclear antibodies and rheumatoid factor may help in the differential diagnosis. However, American College of Rheumatology guidelines advise against the routine use of these tests due to the high false-positive rate of these tests.24

Imaging Studies

The diagnosis of osteoarthritis is primarily based on clinical findings. However, imaging may help confirm the diagnosis and also aid in the differential diagnosis. Among imaging methods, radiographic examination remains the method of choice. However, computed tomography (CT) or magnetic resonance imaging (MRI) may provide additional information, in some cases confirming inflammation of surrounding soft tissues.

Differential Diagnosis

Rheumatoid arthritis is the second most common cause of arthritis. However, it is a systemic autoimmune disorder, affecting multiple joints at once. Prolonged morning stiffness involving multiple joints is the hallmark of RA. Also, both sides are usually equally affected. Other signs of severe inflammation include fever and fatigue.32

Additionally, there is a need to differentiate osteoarthritis from other conditions, particularly infections, lupus, and malignancy. In knee osteoarthritis, it is vital to differentiate the condition from traumatic conditions such as injuries to the anterior cruciate ligament, posterior cruciate ligament, lateral collateral ligament, medial lateral ligament, or meniscus.33

Osteoarthritis Guideline Recommendations

American College of Rheumatology Guidelines 2019

Top 5 osteoarthritis management recommendations38:

  1. Strongly recommend exercise and participation in self-management programs
  2. Weight loss and balance-improving exercises like tai chi for knee and hip osteoarthritis
  3. Oral nonsteroidal anti-inflammatory drugs (NSAIDs) as first-line pharmacologic treatment; topical NSAIDs only for knee osteoarthritis
  4. Consider intra-articular steroids for pain management in knee and hip osteoarthritis
  5. Opioids—tramadol is preferred for its safety profile within the class—or the antidepressant duloxetine (conditional recommendation)

Top 5 recommendations against the following therapies38:

  1. Transcutaneous electrical nerve stimulation (TENS; strongly against)
  2. Bisphosphonates, glucosamine, hydroxychloroquine, methotrexate, tumor necrosis factor (TNF) inhibitors, platelet-rich plasma, and stem cell injection (strongly against)
  3. Manual therapy, massage, modified shoes, wedged insoles, and pulsed vibration therapy may have limited benefit, although they may help in some cases (conditionally against)
  4. Vitamin D and fish oil (conditionally against)
  5. Opioids other than tramadol (conditionally against)

Osteoarthritis Management

Nonpharmacologic

Among nonpharmacologic means, exercise therapy is the most effective approach for pain reduction and improving joint movement. In a randomized controlled trial published in The BMJ comprising 786 men and women older than 45 years followed up for a period of 24 months, regular exercise was found to significantly reduce knee pain.34

A Cochrane systematic review also found evidence in favor of exercise therapy in reducing pain and improving physical function in knee osteoarthritis. Although the magnitude of benefit was small, it is comparable to that seen with NSAIDs.35 Similarly, another Cochrane systematic review found that aquatic exercise has beneficial, short-term effects on knee and hip osteoarthritis.36

As obesity is the most significant risk factor for osteoarthritis of weight-bearing joints, even moderate weight loss may help. A systematic review found that weight loss greater than 5% in 20 weeks may help improve osteoarthritis-related disability considerably.37

Guidelines from the American College of Rheumatology (ACR) and Arthritis Foundation strongly recommend exercise, weight loss, tai chi, and using a cane or knee brace for individuals with osteoarthritis. The guidelines also advise that in some conditions, therapeutic heat or cooling, cognitive behavioral therapy, acupuncture, balance training, Kinesio® taping, paraffin, and yoga may also help.38

The ACR guidelines state that there is no benefit from TENS in individuals with knee and/or hip osteoarthritis and strongly recommend against its use. The guidelines also advise against the use of modified shoes, wedged insoles, and pulsed vibration therapy. They also advise against massage and manual therapy for the management of symptoms of osteoarthritis.38

Pharmacologic

When nonpharmacologic means fail to help, a stepwise approach to management should be charted. Acetaminophen is the first-line pain reliever as it is one of the safest analgesics with the least number of severe side effects.24 In addition, add-on therapy with topical agents such as diclofenac gel can be considered (Figure 2).https://e.infogram.com/32353cfd-37c4-4fbb-8763-03f9e5540b22?src=embed

Due to their anti-inflammatory action, NSAIDs may be more effective than acetaminophen for symptoms of osteoarthritis. However, they are also more likely to cause side effects, especially with prolonged use.39 Treatment may be initiated with more commonly available NSAIDs, such as ibuprofen. However, if prolonged use causes gastric issues, proton pump inhibitors may be prescribed concurrently. Naproxen generally does not cause gastric distress. Among the COX-2 inhibitors, low-dose celecoxib is preferred due to its better safety profile.40 Newer COX-2 inhibitors are also effective. 

If the patient does not respond to NSAID therapy, use of tramadol may be considered.24 Duloxetine is another option to consider. Some patients may better tolerate tapentadol due to its different mode of action than tramadol; however, it has much less history of use in osteoarthritis.41 Opioids other than tramadol may help in some instances but should be used with extreme caution due to their known side effects and high risk of dependence.38

Intra-articular injections of corticosteroids or hyaluronic acid may also be used to address symptoms of osteoarthritis. While both treatments have demonstrated efficacy, studies have shown that corticosteroids are more effective in controlling acute pain, whereas hyaluronic acid has a more significant benefit for chronic pain. If the goal of using intra-articular injections is to control acute exacerbation and pain suppression, corticosteroids might be preferred; in relatively stable patients, hyaluronic acid may be tried. Studies have shown that corticosteroids are more effective for the first 8 weeks of treatment; however, after that, there is a greater benefit from hyaluronic acid, with considerable effect continuing for 26 weeks.42

The ACR 2019 guidelines advise against using certain treatment modalities as they have shown no benefit and may instead cause unwanted side effects. These treatments include bisphosphonates including zoledronic acid and alendronate, hydroxychloroquine, methotrexate, TNF inhibitors, interleukin-1 (IL-1) receptor antagonists, platelet-rich plasma, and stem cell injection.38

Surgical

For patients who do not respond to conservative therapy and whose disease continues to progress, causing significant pain and disability, total joint replacement of the knee, hip, or shoulder may be considered. Although other surgical treatments for osteoarthritis exist, their benefits are minimal, and joint replacement remains the preferred surgical treatment. Most prostheses can be expected to last for 15 to 20 years.24

Monitoring for Osteoarthritis Side Effects

As most people living with osteoarthritis are treated with NSAIDs, the risk of developing gastritis is significant. Monitoring of inflammatory markers will help to understand the therapeutic response. Additionally, considering the risk of cardiovascular adverse events associated with COX-2 inhibitors, a cautious approach to their use for osteoarthritis is advised.

Comorbidities

Osteoarthritis has been found to be associated with certain health conditions. Among them, obesity stands out as it is a modifiable risk factor. Individuals with osteoarthritis have at least a 20% greater risk of hypertension, dyslipidemia, back pain, thyroid disorder, depression, peptic ulcer, diabetes, chronic obstructive pulmonary disease, heart disease, peripheral vascular disorder, kidney disease, and neoplasm compared with adults without osteoarthritis.43,44 The cardiovascular and musculoskeletal systems are most commonly affected, leading to hypertension, dyslipidemia, and back pain (Figure 3).https://e.infogram.com/2253c2b6-6113-4c3f-af6b-3b29f2102b9b?src=embed

Complications

The primary complications of osteoarthritis are loss of mobility and functional disability, which are progressive. Osteoarthritis may ultimately lead to severe damage of all joint structures, thus necessitating joint replacement. Additionally, decreased mobility and other lifestyle changes caused by osteoarthritis may considerably increase the risk of cardiovascular ailments, other musculoskeletal disorders, and mood disorders.

Osteoarthritis Patient Education

Patient education has a special place in managing chronic disorders. Patients should be advised to lose bodyweight, as even moderate weight loss of 5% to 7% may help with arthritis and considerably reduce the risk of diabetes and cardiovascular events.

Mild or early-state osteoarthritis can be managed significantly with exercise and intermittent use of medications. Thus, stretching, walking, swimming, aerobics, and other low-impact exercises may help arrest disease progress. 

Adjusting posture — such as learning to sit correctly, using a raised chair or toilet seat, or avoiding repeated motions — may provide relief from osteoarthritis symptoms and improve functionality.

Using supportive devices like canes or grabbers may also assist with daily functioning. 

Osteoarthritis FAQs

Which joints are most commonly affected by osteoarthritis?

Osteoarthritis most commonly affects weight-bearing joints like the knees and hips.

Is osteoarthritis a systemic disorder?

Osteoarthritis is a local disorder of joints. Nonetheless, it may have a relationship with other systemic disorders, especially obesity. It also considerably increases the risk of other systemic disorders including hypertension and diabetes. As such, it would be unwise to visualize it as a localized disorder.

Can osteoarthritis occur in children and adolescents?

Prevalence of osteoarthritis is extremely low in children and adolescents. However, it may occur due to congenital disabilities or as a result of trauma in these age groups.

Who is at increased risk of developing osteoarthritis?

Obesity, defined as a body mass index (BMI) of 30 kg/m2 or higher, is the most significant risk factor contributing to the development of arthritis. Age also increases risk, with the disease most commonly diagnosed between ages 55 and 64.

Can osteoarthritis be prevented?

Osteoarthritis may be minimized, if not outright prevented, through lifestyle intervention. Weight loss and regular exercise with low-impact activities appears to stave off osteoarthritis and many of the diseases associated with it, such as hypertension and diabetes.

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