Osteoarthritis

Definition, Etiology, PathogenesisTop

Osteoarthritis (OA) is caused by biological and mechanical factors that destabilize the complementary processes of degradation and formation of articular cartilage and the subchondral bony plate and eventually involves all tissues of the joint. OA is characterized by arthralgia, limited motion, crepitus, and secondary inflammatory changes of variable severity (eg, with joint effusion) without systemic symptoms. OA may be classified as primary OA (more common; etiology is unknown) or secondary OA (caused by local damage and structural abnormalities of the joint or by systemic diseases). Primary OA typically affects weight-bearing joints (eg, facet joints of the spine, hips, knees, first metatarsophalangeal [MTP] joints) and hands (base of the thumbs, proximal interphalangeal [PIP] joints, distal interphalangeal [DIP] joints). Primary OA usually does not affect the ankle. Secondary OA should be suspected if atypical joints are affected (eg, shoulders, elbows, wrists, metacarpophalangeal [MCP] joints, and ankles).

Causes of secondary OA:

1) Acute or chronic joint trauma.

2) Congenital and developmental causes, such as avascular necrosis of the femoral head in children (Perthes disease), congenital hip dysplasia, slipped capital femoral epiphysis, differences in the length of lower extremities, varus or valgus deformity of lower extremities, joint hypermobility syndrome, dysplasia of joints, dysplasia of bones.

3) Metabolic disorders: Alkaptonuria (ochronosis), hemochromatosis, Wilson disease, Gaucher disease.

4) Endocrine disorders: Acromegaly, thyrotoxicosis, diabetes mellitus, obesity, hypothyroidism.

5) Diseases caused by deposition of calcium salts: Chondrocalcinosis, hydroxyapatite deposition disease.

6) Inflammatory arthritides: Rheumatoid arthritis, psoriatic arthritis/peripheral spondyloarthritis, gout, and other types of inflammatory arthritis.

7) Other bone and joint conditions: Fractures, avascular necrosis, infections, Paget disease, osteopetrosis, osteochondritis dissecans.

8) Neuropathic osteoarthropathy: Charcot joints.

Risk factors: Advanced age, female sex, overweight and obesity, genetic mutations (eg, affecting the type II collagen gene), mechanical factors (eg, occupations requiring frequent knee-bending, professional sports, weakness of the adjacent muscles, prior trauma), proprioceptive dysfunction.

Clinical Features and Natural HistoryTop

Clinical manifestations usually occur after the age of 45 years and are highly variable in severity. They do not always correlate with the degree of joint damage seen on imaging studies:

1) Joint pain is the dominant symptom. It is triggered by weight-bearing and/or motion of the affected joint; in advanced OA, it may be severe and also occur at rest and at night. Pain can be worse during initial movements following a period of immobility and gradually improve with subsequent movements but then intensify with further use. Pain is usually relieved by rest. Associated periarticular soft-tissue involvement (eg, bursitis) can cause pain away from the joint line, whereas pain originating from the joint itself is usually maximal at the joint line.

2) Limited motion of the affected joints with secondary atrophy of local muscles.

3) Other features include transient stiffness lasting <30 minutes (early morning or after inactivity), absence of warmth, crepitus on movement, joint deformity, instability, and occasionally joint effusion.

OA progresses slowly, usually with periods of relapses and remissions. Joint damage is irreversible and the progression is independent of medical therapy. However, both pharmacologic and nonpharmacologic therapy can have beneficial effects on symptoms. Disability depends on the location and severity of lesions.

1. OA of the hip: Pain is usually felt in the groin but may involve the anterior thigh and occasionally the lower back and buttocks. Pain can also radiate to the knee. Limited motion develops early in the course of the disease, usually with internal rotation being the first to be affected. Secondary inflammation of the insertions of the gluteal muscles on the greater trochanter and trochanteric bursitis may develop, causing pain in the lateral parts of the thigh, gluteal muscle atrophy, and relative limb shortening.

2. OA of the knee: Pain is located in the joint and the upper part of the lower leg and is usually worse with weight-bearing and ambulation. Flexion and extension of the joint may produce palpable crepitus. The axis of the limb is almost always abnormal, with varus deformity being more common than valgus deformity. Joint effusion and popliteal cyst (Baker cyst) are frequently seen. Joint outlines may be widened and deformed in advanced cases. Secondary changes include weakness and atrophy of the quadriceps muscles, enthesitis of the lateral collateral ligaments and knee flexors insertions, and pes anserine bursitis; these also cause pain. In patients with advanced OA of the knee, a flexion contracture of the knee can occur. OA can affect any or all compartments of the knee: medial (most common, may be accompanied by varus knee deformity), lateral (less common, may be accompanied by valgus knee deformity), and patellofemoral. Patients with patellofemoral OA may have more pain going downstairs than upstairs.

3. OA of the hands: Joint pain, brief morning stiffness (up to 30 minutes), and stiffness after periods of inactivity may occur, with limited correlation between symptom severity and imaging findings. Function can be affected, varying from mild to marked impairment. OA affects both hands, typically causing bony enlargement of the affected joints. The most frequently affected joints are DIP and PIP joints of the second to fifth digits as well as the base of the thumbs (the first carpometacarpal joint). Characteristic deformities are seen at the DIP joints (Heberden nodes; see Fingers in Rheumatic Diseases), PIP joints (Bouchard nodes; see Fingers in Rheumatic Diseases), or both. Superimposed effusions as well as central joint erosions can occur; this is called erosive or inflammatory OA of the hands.

4. OA of the spine: Facet joint OA often coexists with degeneration of spinal ligaments and degenerative disk disease (loss of disk height, vertebral endplate changes, and osteophyte formation at the vertebral margins). A dominant feature is paraspinal pain, which usually increases on movement. The type and location of lesions (intervertebral disks, facet joints, spinal ligaments) cannot be established on the basis of symptoms alone. Cervical facet OA can cause ipsilateral neck pain, which is aggravated by neck rotation or lateral flexion. Lumbar facet OA can produce localized lumbar pain, which may radiate unilaterally or bilaterally to the buttocks, groin, and thighs.

In patients with diffuse idiopathic skeletal hyperostosis (DISH), another noninflammatory disease (also known as Forestier disease), significant bony deposition occurs. Large osteophytes at the corners of vertebral bodies can form bony bridges and often can be misdiagnosed as ankylosing spondylitis. Calcification of spinal ligaments is common. Such soft-tissue calcification is not typical of OA. Pain is dull and of variable severity, and flexibility of the spine is significantly impaired.

5. OA may affect other joints, including the shoulders, acromioclavicular joints, ankle joints, sacroiliac joints, and temporomandibular joints. OA of multiple joints (so-called generalized OA) involves ≥3 of the joints listed above.

DiagnosisTop

Diagnostic Tests

1. Joint radiographs reveal characteristic features: joint space narrowing caused by cartilage destruction, subchondral cysts (geodes) caused by bone destruction, sclerosis of the subchondral bony plate, and osteophytes at the joint margins. The severity of radiographic changes in patients with OA may be classified using the Kellgren-Lawrence scale (Table 1). In inflammatory or erosive OA of the hands, central erosions can appear in the PIP and DIP joints, creating the classic gull-wing appearance on radiographs.

2. Other imaging studies (computed tomography [CT], magnetic resonance imaging [MRI], ultrasonography, scintigraphy) may be useful in differentiating OA from other joint and bone disorders but are often not required. MRI may reveal very early lesions, which precede clinical and radiographic manifestations.

Diagnostic Criteria

Diagnosis is based on symptoms accompanied by characteristic radiographic features. However, in the presence of typical signs and symptoms in the at-risk age group, OA can be diagnosed without radiography and/or laboratory investigations.

Differential Diagnosis

Clinical and radiographic features of OA are very characteristic and for that reason differentiating OA from other joint disorders is rarely necessary. However, conditions such as calcium pyrophosphate deposition disease, synovial osteochondromatosis, and avascular necrosis of the femoral head should be considered where appropriate. If secondary OA is suspected (causes: see Definition, Etiology, Pathogenesis, above), underlying etiologies should be evaluated. In patients with inflammatory OA of the hands, and particularly with erosions on radiographs, differential diagnosis should include rheumatoid arthritis, psoriatic arthritis, and gout.

TreatmentTop

The main goal of treatment is pain relief and maintaining the best possible functional status.

Nonpharmacologic Management

1. Patient education.

2. Nutritional management to reduce body weight in overweight or obese patients.

3. Physiotherapy, mainly kinesiotherapy aimed at maintaining joint motion and muscle strength. This may also reduce pain severity.

4. Orthopedic aids, such as walking sticks, crutches, corrective shoe insoles, limb axis correction devices or braces, knee joint stabilizers (including elastic bands), and external correction (medialization) of the patella.

5. Surgical treatment:

1) For patients with severe pain or significant disability caused by OA of the hip or knee, arthroplasty is the key treatment modality. It markedly improves the patient’s quality of life. Patellectomy, osteotomy to correct limb axis, and arthrodesis (joint fixation) are currently rarely performed.

2) Trapeziectomy can be considered for severe OA at the thumb base arthroplasty or arthrodesis, for severe OA of the interphalangeal joints of the hand.

Pharmacotherapy

1. Analgesics:

1) Topical NSAIDs can be used as first-line or adjunctive therapy.

2) For systemic therapy, start with oral acetaminophen (INN paracetamol) up to a maximum dose of 3 g/d (in long-term treatment use lower doses).Evidence 1Strong recommendation (benefits clearly outweigh downsides; right action for all or almost all patients). Moderate Quality of Evidence (moderate confidence that we know true effects of the intervention). Quality of Evidence lowered due to indirectness (short median trial duration of only 6 weeks). Towheed TE, Maxwell L, Judd MG, Catton M, Hochberg MC, Wells G. Acetaminophen for osteoarthritis. Cochrane Database Syst Rev. 2006 Jan 25;(1):CD004257. Review. PubMed PMID: 16437479.

3) If acetaminophen is ineffective, administer a nonsteroidal anti-inflammatory drug (NSAID) at the lowest effective dose and for the shortest possible time (Table 2; note the adverse effects and contraindications [eg, active peptic ulcer disease, severe renal or liver failure, drug hypersensitivity, bleeding]).Evidence 2Strong recommendation (benefits clearly outweigh downsides; right action for all or almost all patients). High Quality of Evidence (high confidence that we know true effects of the intervention). Bannuru RR, Schmid CH, Kent DM, Vaysbrot EE, Wong JB, McAlindon TE. Comparative effectiveness of pharmacologic interventions for knee osteoarthritis: a systematic review and network meta-analysis. Ann Intern Med. 2015 Jan 6;162(1):46-54. doi: 10.7326/M14-1231. Review. PubMed PMID: 25560713. Suggested principles of choosing NSAIDs on the basis of the risk of gastrointestinal (GI) complications and cardiovascular risk are as follows:

a) In patients with a low GI risk and low cardiovascular risk, you can use any NSAID.

b) In patients with a low GI risk and high cardiovascular risk, use naproxen as the first-line agent. To achieve maximal gastric protection, you may add a proton pump inhibitor.

c) In patients with a high GI risk and low cardiovascular risk, celecoxib is the agent of choice.

d) In patients with a high GI risk and high cardiovascular risk, you can use nonpharmacologic management in combination with a medium-dose acetaminophen (up to 2 g/d).

e) In patients receiving long-term acetylsalicylic acid treatment (eg, in prevention of myocardial infarction), avoid ibuprofen.

4) We avoid opioids for chronic pain management of osteoarthritis due to their overall small effect on pain over placebo and risk of adverse effects, including addiction, overdose, somnolence, and vertigo/dizziness, which may increase the risk of falls and fractures.Evidence 3Strong recommendation (downsides clearly outweigh benefits; right action for all or almost all patients). High Quality of Evidence (high confidence that we know true effects of the intervention). Note the authors’ conclusions: “The small mean benefit of non-tramadol opioids are contrasted by significant increases in the risk of adverse events. For the pain outcome in particular, observed effects were of questionable clinical relevance since the 95% CI did not include the minimal clinically important difference of 0.37 SMDs, which corresponds to 0.9 cm on a 10-cm VAS.” da Costa BR, Nüesch E, Kasteler R, et al. Oral or transdermal opioids for osteoarthritis of the knee or hip. Cochrane Database Syst Rev. 2014 Sep 17;(9):CD003115. doi: 10.1002/14651858.CD003115.pub4. Review. PubMed PMID: 25229835. However, in patients in whom NSAIDs are contraindicated, not tolerated, or ineffective, and where other pain management modalities have failed, or for short-term use in patients with severe and disabling symptoms, some clinicians try opioids, starting with weak opioids (see Pain Management: Basic Principles).

2. Glucocorticoid injections: When analgesics are not sufficient, intra-articular glucocorticoid injections may be considered in patients with moderate-severe symptoms.Evidence 4Weak recommendation (benefits likely outweigh downsides, but the balance is close or uncertain; an alternative course of action may be better for some patients). Moderate Quality of Evidence (moderate confidence that we know true effects of the intervention). Quality of Evidence lowered due to the risk of bias and presence of heterogeneity. Jüni P, Hari R, Rutjes AW, et al. Intra-articular corticosteroid for knee osteoarthritis. Cochrane Database Syst Rev. 2015 Oct 22;(10):CD005328. doi: 10.1002/14651858.CD005328.pub3. Review. PubMed PMID: 26490760. Patients should be counselled about the potential risk of avascular necrosis and infection (particular caution should be taken with hip injections). If repeat injections are required in the same joint, these should be done at least 3 to 4 months apart (maximum 3 times per year). No good quality data exist on a lifelong limit of injections and patterns of practice may vary.

3. Symptomatic slow-acting drugs in osteoarthritis (SYSADOA): Glucosamine and chondroitin are widely used but are of uncertain benefit; some trials suggest a small effect of pain improvement. In patients who wish to try these agents, we do not object, given their relative safety.Evidence 5Weak recommendation (benefits likely outweigh downsides, but the balance is close or uncertain; an alternative course of action may be better for some patients). Moderate Quality of Evidence (moderate confidence that we know true effects of the intervention). Quality of Evidence lowered due to the risk of bias and imprecision (small effect size that persisted in some sensitivity analyses and not in others). Towheed TE, Maxwell L, Anastassiades TP, et al. Glucosamine therapy for treating osteoarthritis. Cochrane Database Syst Rev. 2005 Apr 18;(2):CD002946. Review. PubMed PMID: 15846645. Singh JA, Noorbaloochi S, MacDonald R, Maxwell LJ. Chondroitin for osteoarthritis. Cochrane Database Syst Rev. 2015 Jan 28;1:CD005614. doi: 10.1002/14651858.CD005614.pub2. Review. PubMed PMID: 25629804; PubMed Central PMCID: PMC4881293. If pain is not reduced and functional improvement is not achieved after 6 months, discontinuation of SYSADOA is justified.

4. Hyaluronic acid injections: A trial of intra-articular hyaluronate injections in patients who have had inadequate response to or intolerance of acetaminophen, NSAIDs, and intra-articular glucocorticoids may be considered.Evidence 6Weak recommendation (benefits likely outweigh downsides, but the balance is close or uncertain; an alternative course of action may be better for some patients). Moderate Quality of Evidence (moderate confidence that we know true effects of the intervention). Quality of Evidence lowered due to the risk of bias. Bannuru RR, Natov NS, Dasi UR, Schmid CH, McAlindon TE. Therapeutic trajectory following intra-articular hyaluronic acid injection in knee osteoarthritis--meta-analysis. Osteoarthritis Cartilage. 2011 Jun;19(6):611-9. doi: 10.1016/j.joca.2010.09.014. Epub 2011 Apr 9. Review. PubMed PMID: 21443958. Rutjes AW, Jüni P, da Costa BR, Trelle S, Nüesch E, Reichenbach S. Viscosupplementation for osteoarthritis of the knee: a systematic review and meta-analysis. Ann Intern Med. 2012 Aug 7;157(3):180-91. doi: 10.7326/0003-4819-157-3-201208070-00473. Review. PubMed PMID: 22868835. Note that in patients with OA, asymptomatic accumulation of calcium pyrophosphate crystals in joint cartilage may occur. In such cases, an injection of hyaluronic acid of high molecular weight may precipitate acute arthritis; therefore, medium-molecular-weight hyaluronic acid may be better tolerated. If effective, injections can be repeated every 6 months, although the efficacy of repeated courses and their frequency have not been adequately evaluated.

5. Serotonin and norepinephrine reuptake inhibitors (eg, duloxetine, milnacipran) also have analgesic effects via central pain modulation and may be tried in patients with chronic pain persisting despite the above-listed measures.

TablesTop