Osteoarthritis

Osteoarthritis (OA) is the most common form of arthritis, and is due to cartilage Cartilage Cartilage is a type of connective tissue derived from embryonic mesenchyme that is responsible for structural support, resilience, and the smoothness of physical actions. Perichondrium (connective tissue membrane surrounding cartilage) compensates for the absence of vasculature in cartilage by providing nutrition and support. Cartilage destruction and changes of the subchondral bone Bone Bone is a compact type of hardened connective tissue composed of bone cells, membranes, an extracellular mineralized matrix, and central bone marrow. The 2 primary types of bone are compact and spongy. Structure of Bones. The risk of developing this disorder increases with age, obesity Obesity Obesity is a condition associated with excess body weight, specifically with the deposition of excessive adipose tissue. Obesity is considered a global epidemic. Major influences come from the western diet and sedentary lifestyles, but the exact mechanisms likely include a mixture of genetic and environmental factors. Obesity, and repetitive joint use or trauma. Patients develop gradual joint pain Pain Pain has accompanied humans since they first existed, first lamented as the curse of existence and later understood as an adaptive mechanism that ensures survival. Pain is the most common symptomatic complaint and the main reason why people seek medical care. Physiology of Pain, stiffness lasting < 30 minutes, and decreased range of motion. Physical exam may reveal crepitus with joint motion and osteophyte formation (Heberden’s and Bouchard’s nodes). The diagnosis is clinical and supported with radiographic joint findings. Management includes conservative measures, analgesic medications, glucocorticoid intra-articular injections, and surgery for advanced disease.

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Editorial responsibility: Stanley Oiseth, Lindsay Jones, Evelin Maza

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Epidemiology and Etiology

Epidemiology

  • Most common arthropathy (> 70% of all arthritis)
  • Incidence: approximately 195 cases per 100,000 people worldwide
  • Prevalence increases with age.
    • 80%–90% of individuals < 65 years have radiographic osteoarthritis (OA).
    • Symptoms are generally not noticed until after the age of 50.
  • Women are more commonly affected.

Classification and etiology

  • Primary OA: 
    • Idiopathic
    • Nodal OA
  • Secondary OA: 
    • Trauma or surgery
    • Congenital disorders
      • Scoliosis Scoliosis Scoliosis is a structural alteration of the vertebral column characterized by a lateral spinal curvature of greater than 10 degrees in the coronal plane. Scoliosis can be classified as idiopathic (in most cases) or secondary to underlying conditions. Scoliosis
      • Epiphyseal dysplasia
      • Legg-Calve-Perthes disease
      • Joint hypermobility
      • Slipped femoral capital epiphysis Epiphysis The head of a long bone that is separated from the shaft by the epiphyseal plate until bone growth stops. At that time, the plate disappears and the head and shaft are united. Structure of Bones
      • Congenital hip dislocation
    • Metabolic disorders
      • Hemochromatosis
      • Wilson’s disease
      • Crystal deposition disease ( gout Gout Gout is a heterogeneous metabolic disease associated with elevated serum uric acid levels (> 6.8 mg/dL) and abnormal deposits of monosodium urate in tissues. The condition is often familial and is initially characterized by painful, recurring, and usually monoarticular acute arthritis, or "gout flare," followed later by chronic deforming arthritis. Gout)
      • Hemoglobinopathies ( thalassemia Thalassemia Thalassemia is a hereditary cause of microcytic hypochromic anemia and results from a deficiency in either the α or β globin chains, resulting in hemoglobinopathy. The presentation of thalassemia depends on the number of defective chains present and can range from being asymptomatic to rendering the more severely affected patients to be transfusion dependent. Thalassemia)
    • Infection
    • Bone disorders
      • Paget’s disease
      • Osteonecrosis
    • Neuropathic (Charcot’s joint)
      • Diabetes mellitus Diabetes mellitus Diabetes mellitus (DM) is a metabolic disease characterized by hyperglycemia and dysfunction of the regulation of glucose metabolism by insulin. Type 1 DM is diagnosed mostly in children and young adults as the result of autoimmune destruction of β cells in the pancreas and the resulting lack of insulin. Type 2 DM has a significant association with obesity and is characterized by insulin resistance. Diabetes Mellitus
      • Syphilis Syphilis Syphilis is a bacterial infection caused by the spirochete Treponema pallidum pallidum (T. p. pallidum), which is usually spread through sexual contact. Syphilis has 4 clinical stages: primary, secondary, latent, and tertiary. Syphilis

Risk factors

  • Age
  • Obesity
  • Sex
  • Genetics Genetics Genetics is the study of genes and their functions and behaviors. Basic Terms of Genetics and family history
  • Physical activity and repetitive use
  • Muscle weakness or dysfunction

Related videos

Pathophysiology

  • Hypertrophic repair of articular cartilage Cartilage Cartilage is a type of connective tissue derived from embryonic mesenchyme that is responsible for structural support, resilience, and the smoothness of physical actions. Perichondrium (connective tissue membrane surrounding cartilage) compensates for the absence of vasculature in cartilage by providing nutrition and support. Cartilage: mechanical stress → cartilage Cartilage Cartilage is a type of connective tissue derived from embryonic mesenchyme that is responsible for structural support, resilience, and the smoothness of physical actions. Perichondrium (connective tissue membrane surrounding cartilage) compensates for the absence of vasculature in cartilage by providing nutrition and support. Cartilage damage → ↑ proteoglycan and collagen synthesis → swelling of joint cartilage Cartilage Cartilage is a type of connective tissue derived from embryonic mesenchyme that is responsible for structural support, resilience, and the smoothness of physical actions. Perichondrium (connective tissue membrane surrounding cartilage) compensates for the absence of vasculature in cartilage by providing nutrition and support. Cartilage
  • Cartilage destruction:
    • Continued damage → ↑ chondrocyte proliferation and activity → matrix metalloproteinase production → matrix degradation
      • Inflammatory mediators and matrix protein fragments continue chondrocyte stimulation.
      • Ultimately leads to chondrocyte death
    • ↓ collagen and proteoglycans → ↓ cartilage Cartilage Cartilage is a type of connective tissue derived from embryonic mesenchyme that is responsible for structural support, resilience, and the smoothness of physical actions. Perichondrium (connective tissue membrane surrounding cartilage) compensates for the absence of vasculature in cartilage by providing nutrition and support. Cartilage elasticity → ↓ joint integrity
    • Loss of cartilage Cartilage Cartilage is a type of connective tissue derived from embryonic mesenchyme that is responsible for structural support, resilience, and the smoothness of physical actions. Perichondrium (connective tissue membrane surrounding cartilage) compensates for the absence of vasculature in cartilage by providing nutrition and support. Cartilage → ↓ joint space → bone Bone Bone is a compact type of hardened connective tissue composed of bone cells, membranes, an extracellular mineralized matrix, and central bone marrow. The 2 primary types of bone are compact and spongy. Structure of Bones becomes denuded
  • Subchondral bone Bone Bone is a compact type of hardened connective tissue composed of bone cells, membranes, an extracellular mineralized matrix, and central bone marrow. The 2 primary types of bone are compact and spongy. Structure of Bones response:
    • Articulation of exposed bone Bone Bone is a compact type of hardened connective tissue composed of bone cells, membranes, an extracellular mineralized matrix, and central bone marrow. The 2 primary types of bone are compact and spongy. Structure of Bones with an opposing surface → ↑ stress on the bone Bone Bone is a compact type of hardened connective tissue composed of bone cells, membranes, an extracellular mineralized matrix, and central bone marrow. The 2 primary types of bone are compact and spongy. Structure of Bones
    • Vascular invasion and ↑ cellularity → bone Bone Bone is a compact type of hardened connective tissue composed of bone cells, membranes, an extracellular mineralized matrix, and central bone marrow. The 2 primary types of bone are compact and spongy. Structure of Bones becomes thickened and dense (subchondral sclerosis)
    • Chronic impaction and osseous necrosis → cystic degeneration (subchondral cysts)
    • Osseous metaplasia and ossification of connective tissue Connective tissue Connective tissues originate from embryonic mesenchyme and are present throughout the body except inside the brain and spinal cord. The main function of connective tissues is to provide structural support to organs. Connective tissues consist of cells and an extracellular matrix. Connective Tissue → outgrowth of new bone Bone Bone is a compact type of hardened connective tissue composed of bone cells, membranes, an extracellular mineralized matrix, and central bone marrow. The 2 primary types of bone are compact and spongy. Structure of Bones (osteophytes)
Osteoarthritis of synovial joint

Pathology of osteoarthritis
Destruction of cartilage Cartilage Cartilage is a type of connective tissue derived from embryonic mesenchyme that is responsible for structural support, resilience, and the smoothness of physical actions. Perichondrium (connective tissue membrane surrounding cartilage) compensates for the absence of vasculature in cartilage by providing nutrition and support. Cartilage leads to decreased joint space. With severe destruction, bone Bone Bone is a compact type of hardened connective tissue composed of bone cells, membranes, an extracellular mineralized matrix, and central bone marrow. The 2 primary types of bone are compact and spongy. Structure of Bones becomes denuded.

Image: “” by Phil Schatz. License: CC BY 4.0

Clinical Presentation

Commonly affected joints

  • Hands:
    • Proximal interphalangeal (PIP) joints
    • Distal interphalangeal (DIP) joints
    • 1st carpometacarpal Carpometacarpal The articulations between the carpal bones and the metacarpal bones. Wrist Joint (CMC) joints
  • Hips 
  • Knees
  • Spine:
    • Intervertebral discs
    • Zygapophyseal (facet) joints
  • Feet: 1st metatarsophalangeal (MTP) joints

Symptoms

  • Joint pain Pain Pain has accompanied humans since they first existed, first lamented as the curse of existence and later understood as an adaptive mechanism that ensures survival. Pain is the most common symptomatic complaint and the main reason why people seek medical care. Physiology of Pain
    • Gradual onset
    • Asymmetric
    • More severe with: 
      • Activity
      • Weight bearing
    • Relieved with rest
    • Later in the disease: 
      • Pain is more constant.
      • Affects sleep Sleep Sleep is a reversible phase of diminished responsiveness, motor activity, and metabolism. This process is a complex and dynamic phenomenon, occurring in 4-5 cycles a night, and generally divided into non-rapid eye movement (NREM) sleep and REM sleep stages. Physiology of Sleep and level of activity
  • Morning stiffness
    • Duration < 30 minutes
    • Improves with movement
  • Inguinal pain Pain Pain has accompanied humans since they first existed, first lamented as the curse of existence and later understood as an adaptive mechanism that ensures survival. Pain is the most common symptomatic complaint and the main reason why people seek medical care. Physiology of Pain due to hip involvement
  • Restricted joint movement
  • Sensation of joint instability and locking
  • Radicular pain Pain Pain has accompanied humans since they first existed, first lamented as the curse of existence and later understood as an adaptive mechanism that ensures survival. Pain is the most common symptomatic complaint and the main reason why people seek medical care. Physiology of Pain results from:
    • Spondylolisthesis
    • Nerve impingement

Physical exam

  • Joint line tenderness
  • Limited range of motion (ROM)
  • Crepitus with passive ROM
  • Evidence of osteophytes
    • DIP joints: Heberden’s nodes
    • PIP joints: Bouchard’s nodes
    • First CMC joint: thumb squaring
  • Synovitis 
    • Seen in erosive OA
      • An inflammatory subset of primary OA
      • Etiology is unknown.
    • Signs:
      • Soft-tissue swelling
      • Warm
  • Popliteal or Baker’s cyst
  • Knee varus or valgus deformities

Diagnosis

Imaging

Osteoarthritis is a clinical diagnosis that is confirmed with imaging.

  • Radiography
    • Classic findings:
      • Joint space narrowing
      • Subchondral sclerosis
      • Subchondral cysts
      • Osteophytes
      • “Seagull wing” appearance in erosive OA (due to central subchondral erosions)
    • Insensitive for early disease
    • Findings do not correlate well with symptoms.
  • Magnetic resonance imaging (MRI)
    • More sensitive for early disease
    • Additional findings:
      • Cartilage defects
      • Bone marrow Bone marrow Bone marrow, the primary site of hematopoiesis, is found in the cavities of cancellous bones and the medullary canals of long bones. There are 2 types: red marrow (hematopoietic with abundant blood cells) and yellow marrow (predominantly filled with adipocytes). Composition of Bone Marrow lesions
      • Joint effusions

Supporting workup

The following tests are not used for the diagnosis of OA, but are used to exclude other causes of arthritis.

  • Arthrocentesis with synovial fluid analysis
    • Non-inflammatory with a WBC count < 2,000 cells/μL
    • Crystal analysis to rule out gout Gout Gout is a heterogeneous metabolic disease associated with elevated serum uric acid levels (> 6.8 mg/dL) and abnormal deposits of monosodium urate in tissues. The condition is often familial and is initially characterized by painful, recurring, and usually monoarticular acute arthritis, or "gout flare," followed later by chronic deforming arthritis. Gout and pseudogout
  • Laboratory testing 
    • Negative rheumatoid factor (RF) and anti-cyclic citrullinated peptide (anti-CCP)
    • Normal erythrocyte sedimentation rate (ESR) or C-reactive protein (CRP)
    • Negative antinuclear antibody (ANA)

Management

The goals of management include alleviating pain Pain Pain has accompanied humans since they first existed, first lamented as the curse of existence and later understood as an adaptive mechanism that ensures survival. Pain is the most common symptomatic complaint and the main reason why people seek medical care. Physiology of Pain and minimizing the loss of physical function.

Management of osteoarthritis

Osteoarthritis management flowchart
Patients start with conservative measures (weight loss and physical therapy). If symptoms do not improve, or if they worsen, management progresses through this flowchart. Surgery is reserved for patients with severe, unrelenting disease.

Image by Lecturio.

General conservative measures

  • Lifestyle modifications: 
    • Minimize weight bearing.
    • Avoid a slumping posture while sitting.
    • Sleep on a firm bed.
    • Wear supportive shoes or orthoses.
  • Weight loss
  • Physiotherapy to increase: 
    • Strength
    • Flexibility
    • Range of motion
    • Endurance
  • Assistive devices: 
    • Unload or redistribute the load on the joint.
    • Cane, brace, splints, and taping
  • Hot and cold therapy

Medical management

  • Topical capsaicin
  • Acetaminophen Acetaminophen Acetaminophen is an over-the-counter nonopioid analgesic and antipyretic medication and the most commonly used analgesic worldwide. Despite the widespread use of acetaminophen, its mechanism of action is not entirely understood. Acetaminophen
  • Oral and topical nonsteroidal anti-inflammatory drugs (NSAIDs)
  • Muscle relaxants
    • Cyclobenzaprine, methocarbamol
    • Relieve pain Pain Pain has accompanied humans since they first existed, first lamented as the curse of existence and later understood as an adaptive mechanism that ensures survival. Pain is the most common symptomatic complaint and the main reason why people seek medical care. Physiology of Pain from strained muscles
    • Use caution in elderly patients.
  • Duloxetine
    • Can be used in patients with contraindications to NSAIDs
    • Alternative for those who do not respond to the above interventions
  • Corticosteroids
    • Should not be used chronically
    • Can be used orally or as an intra-articular injection
  • Hyaluronic acid
    • Intra-articular injection
    • Controversial, and evidence is limited
  • Supplements
    • Glucosamine, chondroitin
    • Evidence is limited.
  • Opioids Opioids Opiates are drugs that are derived from the sap of the opium poppy. Opiates have been used since antiquity for the relief of acute severe pain. Opioids are synthetic opiates with properties that are substantially similar to those of opiates. Opioid Analgesics
    • Can be considered for short-term use
    • For patients who fail or are not candidates for other treatments
    • Consider referral to a chronic pain management Pain Management Pain is defined as an unpleasant sensory and emotional experience associated with actual or potential tissue damage. Pain is a subjective experience. Acute pain lasts < 3 months and typically has a specific, identifiable cause. Pain Management clinic.

Surgical management

  • Reserved for patients with advanced disease who have failed other treatments
  • Total joint arthroplasty (replacement) is the most common procedure.

Differential Diagnosis

  • Rheumatoid arthritis Rheumatoid arthritis Rheumatoid arthritis (RA) is a symmetric, inflammatory polyarthritis and chronic, progressive, autoimmune disorder. Presentation occurs most commonly in middle-aged women with joint swelling, pain, and morning stiffness (often in the hands). Rheumatoid Arthritis: an autoimmune disease of the joints, causing an inflammatory and destructive arthritis. Patients typically have swelling and pain Pain Pain has accompanied humans since they first existed, first lamented as the curse of existence and later understood as an adaptive mechanism that ensures survival. Pain is the most common symptomatic complaint and the main reason why people seek medical care. Physiology of Pain of the peripheral joints (e.g., hands, wrists, knees, ankles). The DIP joints are generally spared, and morning stiffness typically lasts > 60 minutes. Diagnosis is based on the clinical picture, inflammatory markers, RF, and anti-CCP. Management starts with glucocorticoids Glucocorticoids Glucocorticoids are a class within the corticosteroid family. Glucocorticoids are chemically and functionally similar to endogenous cortisol. There are a wide array of indications, which primarily benefit from the antiinflammatory and immunosuppressive effects of this class of drugs. Glucocorticoids, disease-modifying antirheumatic drugs Disease-modifying antirheumatic drugs Disease-modifying antirheumatic drugs are antiinflammatory medications used to manage rheumatoid arthritis. The medications slow, but do not cure, the progression of the disease. The medications are classified as either synthetic or biologic agents and each has unique mechanisms of action and side effects. Disease-modifying Antirheumatic Drugs (DMARDs), and NSAIDs.
  • Reactive arthritis Reactive arthritis Reactive arthritis is a seronegative autoimmune spondyloarthropathy that occurs in response to a previous gastrointestinal (GI) or genitourinary (GU) infection. The disease manifests as asymmetric oligoarthritis (particularly of large joints in the lower extremities), enthesopathy, dactylitis, and/or sacroiliitis. Reactive Arthritis: a spondyloarthropathy that is often precipitated by a gastrointestinal or genitourinary infection. Patients may present with an asymmetric arthritis, typically of the lower extremities. Reactive arthritis Reactive arthritis Reactive arthritis is a seronegative autoimmune spondyloarthropathy that occurs in response to a previous gastrointestinal (GI) or genitourinary (GU) infection. The disease manifests as asymmetric oligoarthritis (particularly of large joints in the lower extremities), enthesopathy, dactylitis, and/or sacroiliitis. Reactive Arthritis can be associated with fever Fever Fever is defined as a measured body temperature of at least 38°C (100.4°F). Fever is caused by circulating endogenous and/or exogenous pyrogens that increase levels of prostaglandin E2 in the hypothalamus. Fever is commonly associated with chills, rigors, sweating, and flushing of the skin. Fever, tendinitis, enthesitis, mucocutaneous ulcers, and conjunctivitis Conjunctivitis Conjunctivitis is a common inflammation of the bulbar and/or palpebral conjunctiva. It can be classified into infectious (mostly viral) and noninfectious conjunctivitis, which includes allergic causes. Patients commonly present with red eyes, increased tearing, burning, foreign body sensation, and photophobia. Conjunctivitis. Diagnosis is clinical. Management includes NSAIDs, DMARDs, and treatment of the infection. 
  • Psoriatic arthritis: a spondyloarthropathy that occurs in patients with psoriasis Psoriasis Psoriasis is a common T-cell-mediated inflammatory skin condition. The etiology is unknown, but is thought to be due to genetic inheritance and environmental triggers. There are 4 major subtypes, with the most common form being chronic plaque psoriasis. Psoriasis. This inflammatory arthritis is frequently asymmetric. Small and large joints are involved, including the DIP joints and the sacroiliac spine. Enthesopathy and dactylitis are also seen. The diagnosis is clinical, and should be suspected in patients with psoriasis Psoriasis Psoriasis is a common T-cell-mediated inflammatory skin condition. The etiology is unknown, but is thought to be due to genetic inheritance and environmental triggers. There are 4 major subtypes, with the most common form being chronic plaque psoriasis. Psoriasis. Management includes DMARDs and biologic agents.
  • Gout: a disease caused by hyperuricemia that leads to arthritis from precipitation of monosodium urate crystals in the joints. Gout is often monoarticular, and usually involves pain Pain Pain has accompanied humans since they first existed, first lamented as the curse of existence and later understood as an adaptive mechanism that ensures survival. Pain is the most common symptomatic complaint and the main reason why people seek medical care. Physiology of Pain, tenderness, swelling, erythema, and warmth of the first MTP joint. The diagnosis is made with identification of negatively birefringent, needle-shaped crystals in the synovial fluid. Management includes NSAIDs, colchicine, corticosteroids, and uric acid reduction with allopurinol.
  • Pseudogout: intra-articular calcium pyrophosphate deposition. The etiology is not clear. Patients present with acute flares of joint swelling, warmth, and pain Pain Pain has accompanied humans since they first existed, first lamented as the curse of existence and later understood as an adaptive mechanism that ensures survival. Pain is the most common symptomatic complaint and the main reason why people seek medical care. Physiology of Pain. Pseudogout usually affects larger joints, such as the knee. Diagnosis is with identification of positively birefringent, rhomboid crystals in the synovial fluid. Management includes NSAIDs, corticosteroids, and colchicine.
  • Septic arthritis Septic arthritis Septic arthritis is an infection of the joint due to direct inoculation, contiguous extension, or hematogenous spread of infectious organisms into the joint space. This process causes an acute, inflammatory, monoarticular arthritis. Septic Arthritis: a joint infection due to bacteria Bacteria Bacteria are prokaryotic single-celled microorganisms that are metabolically active and divide by binary fission. Some of these organisms play a significant role in the pathogenesis of diseases. Bacteriology: Overview (rarely, viruses) in the synovial or periarticular tissues. Patients present with an acute onset of monoarticular swelling, pain Pain Pain has accompanied humans since they first existed, first lamented as the curse of existence and later understood as an adaptive mechanism that ensures survival. Pain is the most common symptomatic complaint and the main reason why people seek medical care. Physiology of Pain, erythema, and warmth. Fever may also be present. Diagnosis is made with synovial fluid analysis, including Gram stain, culture, and WBC count > 20,000 cells/μL. Management includes intravenous antibiotics and drainage of pus from the joint.

References

  1. March, L., and Cross, M. (2020). Epidemiology and risk factors for osteoarthritis. In Ramirez Curtis, M. (Ed.), UpToDate. Retrieved January 11, 2021, from https://www.uptodate.com/contents/epidemiology-and-risk-factors-for-osteoarthritis
  2. Loeser, R.F. (2020). Pathogenesis of osteoarthritis. In Ramirez Curtis, M. (Ed.), UpToDate. Retrieved January 11, 2021, from https://www.uptodate.com/contents/pathogenesis-of-osteoarthritis
  3. Doherty, M., and Abhishek, A. (2019). Clinical manifestations and diagnosis of osteoarthritis. In Ramirez Curtis, M. (Ed.), UpToDate. Retrieved January 11, 2021, from https://www.uptodate.com/contents/clinical-manifestations-and-diagnosis-of-osteoarthritis
  4. Deveza, L.A. (2020). Overview of the management of osteoarthritis. In Ramirez Curtis, M. (Ed.), UpToDate. Retrieved January 11, 2021, from https://www.uptodate.com/contents/overview-of-the-management-of-osteoarthritis
  5. Kontzias, A. (2020). Osteoarthritis (OA). [online] MSD Manual Professional Version. Retrieved January 11, 2021, from https://www.msdmanuals.com/professional/musculoskeletal-and-connective-tissue-disorders/joint-disorders/osteoarthritis-oa
  6. Lozada, C.J., and Culpepper Pace, S.S. (2020). Osteoarthritis. In Diamond, H.S. (Ed.), Medscape. Retrieved January 11, 2021, from https://emedicine.medscape.com/article/330487-overview
  7. Sen, R., and Hurley, J.A. (2020). Osteoarthritis. [online] StatPearls. Retrieved January 12, 2021, from https://www.ncbi.nlm.nih.gov/books/NBK482326/

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