Osteoarthritis, the most common joint disorder, often becomes symptomatic in the 40s and 50s and is nearly universal (although not always symptomatic) by age 80. Only half of patients with pathologic changes of osteoarthritis have symptoms. Below age 40, most large-joint osteoarthritis occurs in men and often results from trauma or anatomic variation (eg, hip dysplasias). Women predominate from age 40 to 70, after which men and women are equally affected.
Classification of Osteoarthritis
Osteoarthritis is classified as primary (idiopathic) or secondary to some known cause.
Primary osteoarthritis may be localized to certain joints (eg, chondromalacia patellae Chondromalacia Patellae Chondromalacia patellae is softening of the cartilage underneath the patella. Chondromalacia patellae often causes generalized knee pain especially when climbing or descending stairs, playing... read more is a mild osteoarthritis that occurs in young people). Primary osteoarthritis is usually subdivided by the site of involvement (eg, hands and feet, knee, hip). If primary osteoarthritis involves multiple joints, it is classified as primary generalized osteoarthritis.
Secondary osteoarthritis results from conditions that change the microenvironment of the cartilage or joint structure. These conditions include significant trauma, congenital joint abnormalities, metabolic defects (eg, hemochromatosis Hereditary Hemochromatosis Hereditary hemochromatosis is a genetic disorder characterized by excessive iron (Fe) accumulation that results in tissue damage. Manifestations can include systemic symptoms, liver disorders... read more , Wilson disease Wilson Disease Wilson disease results in accumulation of copper in the liver and other organs. Hepatic or neurologic symptoms develop. Diagnosis is based on a low serum ceruloplasmin level, high urinary excretion... read more ), infections (causing postinfectious arthritis), endocrine and neuropathic diseases, and disorders that alter the normal structure and function of hyaline cartilage (eg, rheumatoid arthritis Rheumatoid Arthritis (RA) Rheumatoid arthritis is a chronic systemic autoimmune disease that primarily involves the joints. Rheumatoid arthritis causes damage mediated by cytokines, chemokines, and metalloproteases.... read more , gout Gout Gout is a disorder caused by hyperuricemia (serum urate > 6.8 mg/dL [> 0.4 mmol/L]) that results in the precipitation of monosodium urate crystals in and around joints, most often causing recurrent... read more , calcium crystal deposition disease Calcium Pyrophosphate Arthritis Calcium pyrophosphate arthritis (CPP arthritis) involves intra-articular and/or extra-articular deposition of calcium pyrophosphate dihydrate (CPPD) crystals. Manifestations are protean and... read more ).
Pathophysiology of Osteoarthritis
Normal joints have little friction with movement and do not wear out with typical use, overuse, or most trauma. Hyaline cartilage is avascular, aneural, and alymphatic. It is 95% water and extracellular cartilage matrix and only 5% chondrocytes. Chondrocytes have the longest cell cycle in the body (similar to central nervous system and muscle cells). Cartilage health and function depend on compression and release of weight bearing and use (ie, compression pumps fluid from the cartilage into the joint space and into capillaries and venules, whereas release allows the cartilage to reexpand, hyperhydrate, and absorb necessary electrolytes and nutrients).
The trigger of osteoarthritis is most often unknown, but osteoarthritis sometimes begins with tissue damage from mechanical injury (eg, torn meniscus), transmission of inflammatory mediators from the synovium into cartilage, or defects in cartilage metabolism. Obesity triggers some of these defects in cartilage metabolism, leading to cartilage matrix damage and subchondral bone remodeling mediated by adipokines, such as leptin and adipsin, and compounded by mechanical factors due to excess weight. The tissue damage stimulates chondrocytes to attempt repair, which increases production of proteoglycans and collagen. However, efforts at repair also stimulate the enzymes that degrade cartilage, as well as inflammatory cytokines, which are normally present in small amounts. Inflammatory mediators trigger an inflammatory cycle that further stimulates the chondrocytes and synovial lining cells, eventually breaking down the cartilage. Chondrocytes undergo programmed cell death (apoptosis). Once cartilage is destroyed, exposed bone becomes eburnated and sclerotic.
All articular and some periarticular tissues can become involved in osteoarthritis. Subchondral bone stiffens, then undergoes infarction, and develops subchondral cysts. Attempts at bony repair cause subchondral sclerosis and osteophytes at the joint margins. The osteophytes seem to develop in an attempt to stabilize the joint. The synovium becomes mildly inflamed and thickened and produces synovial fluid with less viscosity and greater volume. Periarticular tendons and ligaments become stressed, resulting in tendinitis and contractures. As the joint becomes less mobile, surrounding muscles weaken and become less supportive. Knee menisci, which are partially innervated, fissure and may fragment and contribute to the pain.
Osteoarthritis of the spine can, at the disk level, cause marked thickening and proliferation of the posterior longitudinal ligaments, which are posterior to the vertebral body but anterior to the spinal cord. The result can be transverse bars that encroach on the anterior spinal cord. Hypertrophy and hyperplasia of the ligamenta flava, which are posterior to the spinal cord, often compress the posterior canal, causing lumbar spinal stenosis Symptoms and Signs Lumbar spinal stenosis is narrowing of the lumbar spinal canal causing compression of the nerve rootlets and nerve roots in the cauda equina before their exit from the foramina. It causes positional... read more . In contrast, the anterior and posterior nerve roots, ganglia, and common spinal nerve are relatively well protected in the intervertebral foramina, where they occupy only 25% of the available and well-cushioned space.
Symptoms and Signs of Osteoarthritis
Onset of osteoarthritis is most often gradual, usually beginning with one or a few joints.
Pain is the earliest symptom of osteoarthritis, sometimes described as a deep ache. Pain is usually worsened by weight bearing and relieved by rest but can eventually become constant.
Stiffness follows awakening or inactivity but lasts < 30 minutes and lessens with movement. As osteoarthritis progresses, joint motion becomes restricted, and tenderness and crepitus or grating sensations develop.
Early hypertrophy of cartilage is followed by notable bone, ligament, tendon, capsules, and synovial reaction, along with varying amounts of noninflammatory joint effusion, ultimately resulting in the joint enlargement characteristic of osteoarthritis.
Flexion contractures may develop. Acute or severe synovitis is rare.
Tenderness on palpation and pain on passive motion are relatively late signs. Muscle spasm and contracture add to the pain. Mechanical block by intra-articular loose bodies or abnormally placed menisci can occur and cause locking or catching. Deformity and subluxations can also develop.
Osteoarthritis is usually sporadically progressive but occasionally, with no predictability, stops.
The joints most often affected in generalized osteoarthritis include the following:
Distal interphalangeal (DIP) and proximal interphalangeal (PIP) joints (causing Heberden and Bouchard nodes)
Thumb carpometacarpal joint (the most commonly painful hand joint)
Intervertebral disks and zygapophyseal joints in the cervical and lumbar vertebrae
First metatarsophalangeal joint
Cervical and lumbar spinal osteoarthritis may lead to myelopathy or radiculopathy. However, the clinical signs of myelopathy are usually mild. Lumbar spinal stenosis may cause lower back or leg pain that is worsened by walking (neurogenic claudication, sometimes called pseudoclaudication) or back extension. Radiculopathy can be prominent but is less common because the nerve roots and ganglia are well protected. Insufficiency of the vertebral arteries, infarction of the spinal cord, and dysphagia due to esophageal impingement by cervical osteophytes occasionally occur. Symptoms and signs caused by osteoarthritis in general may also derive from subchondral bone, ligamentous structures, synovium, periarticular bursae, capsules, muscles, tendons, disks, and periosteum, all of which are pain sensitive. Venous pressure may increase within the subchondral bone marrow and cause pain (sometimes called bone angina).
Hip osteoarthritis causes gradual loss of range of motion and is most often symptomatic during weight-bearing activities. Pain may be felt in the inguinal area or greater trochanter or referred to the thigh and knee.
Knee osteoarthritis causes cartilage to be lost (medial loss occurs in 70% of cases). The ligaments become lax and the joint becomes less stable, with local pain arising from the ligaments and tendons.
Erosive osteoarthritis causes synovitis and cysts in the hand. It primarily affects the DIP or PIP joints. The thumb carpometacarpal joints are involved in 20% of hand osteoarthritis, but the metacarpophalangeal joints and wrists are usually spared. At this time, it is uncertain whether erosive interphalangeal osteoarthritis is a variant of hand osteoarthritis or whether it represents a separate entity, such as microcrystalline disease (eg, calcium pyrophosphate arthritis).
Diagnosis of Osteoarthritis
Osteoarthritis should be suspected in patients with gradual onset of symptoms and signs, particularly in older adults. If osteoarthritis is suspected, plain x-rays should be taken of the most symptomatic joints. X-rays generally reveal marginal osteophytes, narrowing of the joint space, increased density of the subchondral bone, subchondral cyst formation, bony remodeling, and joint effusions. Standing weight-bearing Merchant view (tangential view with knee flexed 30°) x-rays of the knees are more sensitive in detecting joint space narrowing. Discrepancy between severity of symptoms and severity of changes in imaging is common.
Laboratory studies are normal in osteoarthritis but occasionally may be required to rule out other disorders or to diagnose an underlying disorder causing secondary osteoarthritis. If osteoarthritis causes joint effusions, synovial fluid analysis can help differentiate it from inflammatory arthritides; in osteoarthritis, synovial fluid is usually clear, viscous, and has ≤ 2000 WBC/mcL.
Osteoarthritis involvement outside the usual joints suggests secondary osteoarthritis; further evaluation may be required to determine the underlying primary disorder (eg, endocrine, metabolic, neoplastic, or biomechanical disorders).
Treatment of Osteoarthritis
Nondrug therapy (eg, education, appropriate weight loss, rehabilitative and supportive measures)
Osteoarthritis treatment goals are relieving pain, maintaining joint flexibility, and optimizing joint and overall function. Primary treatments include physical measures that involve rehabilitation; support devices; exercise for strength, flexibility, and endurance; patient education; and modifications in activities of daily living. Adjunctive therapies include drug treatment and surgery. (See also the 2019 American College of Rheumatology/Arthritis Foundation Guideline for the Management of Osteoarthritis of the Hand, Hip, and Knee for nondrug management of hip and knee osteoarthritis.)
Moderate weight loss in patients with overweight often reduces pain and may even reduce progression of knee osteoarthritis. Rehabilitation techniques are best begun before disability develops.
Exercises (range of motion, isometric, isotonic, isokinetic, postural, strengthening—see Physical Therapy Physical Therapy (PT) Physical therapy aims to improve joint and muscle function (eg, range of motion, strength) and thus improve the patient’s ability to stand, balance, walk, and climb stairs. For example, physical... read more ) maintain range of motion and increase the capacity for tendons and muscles to absorb stress during joint motion. Exercise can sometimes arrest or even reverse hip and knee osteoarthritis. Aquatic exercises are recommended because they spare the joints from stress. Stretching exercises should be done daily.
Immobilization for any prolonged period of time can promote contractures and worsen the clinical course. However, a few minutes of rest (every 4 to 6 hours in the daytime) can help if balanced with exercise and use.
Modifying activities of daily living can help. For example, a patient with lumbar spine, hip, or knee osteoarthritis should avoid soft deep chairs and recliners in which posture is poor and from which rising is difficult. The regular use of pillows under the knees while reclining encourages contractures and should also be avoided. However, pillows placed between the knees can often help relieve radicular back pain. Patients should sit in straight-back chairs without slumping, sleep on a firm bed (perhaps with a bed board), use a car seat shifted forward and designed for comfort, do postural exercises, wear well-supported shoes or athletic shoes, and continue employment and physical activity.
In osteoarthritis of the spine, knee, or thumb carpometacarpal joint, various supports can relieve pain and increase function, but to preserve flexibility, they should be accompanied by specific exercise programs. For medial knee osteoarthritis, orthoses designed to reduce knee load are preferred to lateral wedge insoles, which have yielded equivocal outcomes (1 Treatment references Osteoarthritis is a chronic arthropathy characterized by disruption and potential loss of joint cartilage along with other joint changes, including bone hypertrophy (osteophyte formation). Symptoms... read more ).
In erosive osteoarthritis, range-of-motion exercises done in warm water can help prevent contractures.
Drug therapy is an adjunct to the physical program. Acetaminophen in dosages of up to 1 g orally 4 times a day may relieve pain and is generally safe in the absence of hepatic disease or considerable alcohol intake. More potent analgesics, such as tramadol or rarely opioids, may be required; however, these medications can cause confusion in older patients and are generally avoided. Duloxetine, a serotonin norepinephrine reuptake inhibitor, may modestly reduce pain caused by osteoarthritis. Topical capsaicin has been helpful in relieving pain in superficial joints by disrupting pain transmission.
Nonsteroidal anti-inflammatory drugs (NSAIDs Nonopioid Analgesics Nonopioid and opioid analgesics are the main drugs used to treat pain. Antidepressants, antiseizure drugs, and other central nervous system (CNS)–active drugs may also be used for chronic or... read more ), including selective cyclooxygenase-2 (COX-2) inhibitors or coxibs, may be considered if patients have refractory pain or signs of inflammation (eg, redness, warmth). NSAIDs may be used simultaneously with other analgesics (eg, tramadol, rarely opioids) to provide better relief of symptoms. Topical NSAIDs may be of value for superficial joints, such as the hands and knees. Topical NSAIDs may be of particular value in older patients, because systemic NSAID exposure is reduced, minimizing risk of drug adverse effects. Gastric protection should be considered when using NSAIDs on a regular basis in older patients.
Muscle relaxants such as cyclobenzaprine, metaxalone, and methocarbamol (usually in low doses) occasionally relieve pain that arises from muscles strained by attempting to support osteoarthritis joints, yet strong evidence is lacking unless there is coexistent central sensitization. In older patients, however, they may cause more adverse effects than relief.
Oral corticosteroids should not be given chronically. Intra-articular depot corticosteroids can help relieve pain short-term and increase joint flexibility in some patients; however, a strong placebo effect has been shown in clinical trials. Frequently administered intra-articular injections of corticosteroids increase the risk of cartilage loss (2 Treatment references Osteoarthritis is a chronic arthropathy characterized by disruption and potential loss of joint cartilage along with other joint changes, including bone hypertrophy (osteophyte formation). Symptoms... read more ).
Hyaluronic acid formulations can be injected into the knee and provide some pain relief in some patients for prolonged periods of time. They should not be used more often than every 6 months. The treatment is a series of 1 to 5 weekly injections. However, efficacy of these formulations in patients with x-ray evidence of severe knee osteoarthritis is limited, and they are therefore not recommended unless all other options have failed to provide benefit. Hyaluronic acid formulations are not recommended in hip or shoulder osteoarthritis (3 Treatment references Osteoarthritis is a chronic arthropathy characterized by disruption and potential loss of joint cartilage along with other joint changes, including bone hypertrophy (osteophyte formation). Symptoms... read more ). In some patients, local injection can cause an acute severe inflammatory synovitis. Clinical studies of these drugs have shown a strong placebo effect of intra-articular injection. These injections have no demonstrated disease-modifying effect.
Glucosamine sulfate 1500 mg orally once/day has been suggested to relieve pain and slow joint deterioration; chondroitin sulfate 1200 mg once/day has also been suggested for pain relief. Studies to date have shown mixed efficacy in terms of pain relief, with onset of pain relief often delayed, and no strong effect on preservation of cartilage.
Other adjunctive and experimental therapies
Other adjunctive measures may reduce pain, including massage Massage Therapy In massage therapy (a manipulative and body-based practice), body tissues are manipulated to reduce pain, relieve muscle tension, and reduce stress. The therapeutic value of massage for many... read more , heating pads Heat Treatment of pain and inflammation aims to facilitate movement and improve coordination of muscles and joints. Nondrug treatments include therapeutic exercise, heat, cold, electrical stimulation... read more , weight loss, acupuncture Acupuncture Acupuncture, a therapy within traditional Chinese medicine, is one of the most widely accepted components of integrative therapies in the western world. Specific points on the body are stimulated... read more , and transcutaneous electrical nerve stimulation Electrical stimulation Treatment of pain and inflammation aims to facilitate movement and improve coordination of muscles and joints. Nondrug treatments include therapeutic exercise, heat, cold, electrical stimulation... read more (TENS). Laminectomy, osteotomy, and total joint replacement should be considered if nonsurgical approaches fail.
Experimental therapies that may preserve cartilage or allow chondrocyte grafting are being studied. It is not clear whether using a topical lidocaine 5% patch relieves pain. Flavocoxid, a plant-derived compound, can be tried. Injections of platelet-rich plasma have been shown to be superior to hyaluronic acid for relief of pain in 12-month studies but do not modify disease progression (4 Treatment references Osteoarthritis is a chronic arthropathy characterized by disruption and potential loss of joint cartilage along with other joint changes, including bone hypertrophy (osteophyte formation). Symptoms... read more ). Mesenchymal stem cell therapy for cartilage repair is claimed to yield positive outcomes, especially in knee osteoarthritis (5 Treatment references Osteoarthritis is a chronic arthropathy characterized by disruption and potential loss of joint cartilage along with other joint changes, including bone hypertrophy (osteophyte formation). Symptoms... read more ), but this approach is still considered experimental, with scant evidence supporting its clinical use presently (6 Treatment references Osteoarthritis is a chronic arthropathy characterized by disruption and potential loss of joint cartilage along with other joint changes, including bone hypertrophy (osteophyte formation). Symptoms... read more ). Monoclonal antibodies against nerve growth factor are being tested for chronic pain due to osteoarthritis. However, pilot studies resulted in accelerated osteoarthritis and osteonecrosis, necessitating larger studies with stringent patient inclusion and exclusion criteria.
1. Parkes MJ, Maricar N, Lunt M, et al: Lateral wedge insoles as a conservative treatment for pain in patients with medial knee osteoarthritis: a meta-analysis. JAMA 310(7):722–730, 2013. doi:10.1001/jama.2013.243229
2. McAlindon TE, LaValley MP, Harvey WF, et al: Effect of intra-articular triamcinolone vs saline on knee cartilage volume and pain in patients with knee osteoarthritis: randomized clinical trial. JAMA 317(19):1967–1975, 2017. doi:10.1001/jama.2017.5283
3. Kolasinski SL, Neogi T, Hochberg MC, et al: 2019 American College of Rheumatology/Arthritis Foundation Guideline for the Management of Osteoarthritis of the Hand, Hip, and Knee. Arthritis Care Res (Hoboken) 72(2):149–162, 2020. doi:10.1002/acr.24131
4. Hohmann E, Tetsworth K, Glatt V: Is platelet-rich plasma effective for the treatment of knee osteoarthritis? A systematic review and meta-analysis of level 1 and 2 randomized controlled trials. Eur J Orthop Surg Traumatol, 2020. doi 10.1007/s00590-020-02623-4. doi:10.1007/s00590-020-02623-4
5. Yubo M, Yanyan L, Li L, et al: Clinical efficacy and safety of mesenchymal stem cell transplantation for osteoarthritis treatment: A meta-analysis. PLoS ONE 12(4):e0175449, 2017. doi: 10.1371/journal.pone.0175449. eCollection 2017
6. Pas HI, Winters M, Haisma HJ, et al: Stem cell injections in knee osteoarthritis: a systematic review of the literature. Br J Sports Med 51(15):1125–1133, 2017. doi:10.1136/bjsports-2016-096793
Osteoarthritis, the most common joint disorder, becomes particularly common with age.
Key pathophysiologic features include disruption and loss of joint cartilage and bony hypertrophy.
Osteoarthritis can affect particular joints (sometimes secondary to injury or another joint problem) or be generalized (often as a primary disorder).
Symptoms include gradual onset of joint pain that is worsened by weight-bearing or stress and relieved by rest, and stiffness that lessens with activity.
Confirm the diagnosis with x-ray findings such as marginal osteophytes, narrowing of the joint space, increased density of the subchondral bone, bony remodeling, and sometimes subchondral cyst formation and joint effusion.
Discrepancy between severity of symptoms and severity of changes on imaging is common.
Treat primarily with physical measures that involve rehabilitation; support devices; exercise for strength, flexibility, and endurance; patient education; and modifications in activities of daily living.
Treat adjunctively with drugs (eg, analgesics, nonsteroidal anti-inflammatory drugs, muscle relaxants) and surgery.
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