Highlights & Basics
- Osteoarthritis (OA) is a common and frequently debilitating joint disorder; prevalence increases with age.
- The most commonly affected joints are the knee, hip, hands, feet, and lumbar and cervical spine.
- Presents with joint pain and stiffness that is typically worse with activity.
- Radiographs show loss of joint space, subchondral sclerosis, and osteophytes.
- Treatments are nonpharmacologic and pharmacologic.
- Joint replacement surgery is effective for controlling the pain of OA in advanced disease.
Quick Reference
History & Exam
Key Factors
pain
functional difficulties
knee, hip, hand, or spine involvement
bony deformities
limited range of motion
malalignment
Other Factors
tenderness
crepitus
stiffness
shoulder, elbow, wrist, or ankle involvement
effusion
antalgic gait
Diagnostics Tests
1st Tests to Order
history and physical exam
Other Tests to consider
x-ray of affected joints
serum CRP
serum erythrocyte sedimentation rate (ESR)
rheumatoid factor (RF)
anticyclic citrullinated peptide (anti-CCP) antibody
MRI of affected joints
ultrasound scan
CT
Treatment Options
acute
joint pain: medical management
topical analgesia
nonpharmacologic approaches
intra-articular corticosteroid injections
acetaminophen + topical analgesia
nonpharmacologic approaches
intra-articular corticosteroid injections
NSAID + acetaminophen + topical capsaicin
nonpharmacologic approaches
gastroprotection
intra-articular corticosteroid injections
viscosupplementation with intra-articular hyaluronic acid
opioid + NSAID + acetaminophen + topical capsaicin
duloxetine
nonpharmacologic approaches
gastroprotection
intra-articular corticosteroid injections
viscosupplementation with intra-articular hyaluronic acid
Definition
Classifications
Osteoarthritis classification by disease etiology
- Primary (idiopathic): no preceding injury to the joint; further categorized into localized OA, which mostly affects the hands, knee, hip, or foot (especially the first metatarsophalangeal), or generalized OA, usually affecting the hands and another joint.
- Secondary: an antecedent insult to the joint, such as a congenital abnormality (e.g., congenital hip dysplasia); trauma; inflammatory arthropathies (e.g., rheumatoid arthritis, chronic gout); and ongoing strenuous physical activities or occupations could lead to joint damage over time.
Kellgren-Lawrence radiographic classification of osteoarthritis
- Grade 0 (none): no radiologic findings of osteoarthritis
- Grade 1 (doubtful): doubtful joint space narrowing and possible osteophytic lipping
- Grade 2 (minimal): definite osteophytes and possible joint space narrowing
- Grade 3 (moderate): moderate multiple osteophytes, definite narrowing of joint space and some sclerosis, and possible deformity of bone ends
- Grade 4 (severe): large osteophytes, marked narrowing of joint space, severe sclerosis, and definite deformity of bone ends.
Vignette
Common Vignette 1
Common Vignette 2
Epidemiology
Etiology
Pathophysiology
- Connective tissue growth factor (CTGF) is present in osteophytes of late-stage OA. CTFG is usually upregulated in synovial fluid of OA that stimulates the production of inflammatory cytokines. Evidence has demonstrated CTFG also activates nuclear factor-κB, increases the production of chemokines and cytokines, and upregulates matrix metalloproteinases-3 (MMP-3) that in turn leads to the reduction in proteoglycan contents in joint cartilage. Thereby creating an imbalance in cartilage homeostasis which may contribute to the pathogenesis of OA by developing synovial inflammation and cartilage degradation.[40]
- Matrix metalloproteinases (e.g., collagenase), enzymes that catalyze both collagen and proteoglycan degradation, are found in increased concentrations in OA cartilage.[41]
- Nitric oxide may activate metalloproteinases, thereby playing a role in cartilage degradation.
- Aberrant chondrocyte metabolism is a response to changes in the inflammatory microenvironment and may play a key role in cartilage degeneration and OA progression. Under conditions of environmental stress, chondrocytes shift from oxidative phosphorylation to glycolysis, a process regulated by the AMP-activated protein kinase (AMPK) and mechanistic target of rapamycin (mTOR) pathways.[45]
- Leptin is able to modulate the production of inflammatory mediators in immune cells of patients with OA, and it has been demonstrated to participate in the onset and progression of OA. One meta-analysis reported greater levels of circulating leptin in OA patients compared with the control group, and that synovial leptin levels were greater in patients with OA compared with healthy participants.[46] In addition, LEPR rs113710 polymorphism was linked to an increased risk of developing OA.[46]
- The Janus Kinase 2 (JAK2)/Signal transducer and activator of transcription 3 (STAT3) is a signaling pathway which is instrumental in the osteoarticular system, including cartilage, subchondral bone, and synovium. There is evidence to suggest this signaling plays a significant role in the progression of OA.[47]
Images
Diagnostic Approach
History
Physical examination
OA is essentially a clinical diagnosis
- Activity-related joint pain
- With either no morning joint-related stiffness or morning stiffness that lasts no longer than 30 minutes
- >45 years of age.
- Prolonged morning joint-related stiffness
- History of recent trauma
- Palpable warmth over the joint
- Rapid worsening of symptoms
- Concerns that may suggest infection or malignancy.
Laboratory assessment
Imaging studies
Risk Factors
History & Exam
Tests
Differential Diagnosis
Bursitis
Differentiating Signs/Symptoms
- Greater trochanteric bursitis in the hip and pes anserine bursitis in the knee present with pain over the lateral aspect of the hip and over the medial aspect of the knee, respectively. There is local tenderness in these areas that is usually absent in simple OA.
Differentiating Tests
- Local anesthetic and corticosteroid injection might be therapeutic and diagnostic if it relieves symptoms to a significant degree.
Gout
Differentiating Signs/Symptoms
- The onset of arthritis in gout is usually more acute (over a period of a few hours), but could mimic an exacerbation of acute OA.
- In acute attacks of gout, the affected joint is usually erythematous, hot, and acutely tender.
- Gout commonly involves the foot, especially the first metatarsophalangeal (MTP) joint.
Differentiating Tests
- Arthrocentesis and joint fluid analysis, which shows leukocytes >2000 cells/mm³, and the presence of sodium monourate crystals.
Pseudogout
Differentiating Signs/Symptoms
- The onset of arthritis in pseudogout (calcium pyrophosphate deposition [CPPD]) is usually more acute (over a period of a few hours), but could mimic an exacerbation of acute OA. Associated with other conditions (e.g., hemochromatosis) and results in secondary pseudo-OA, which often involves the metacarpophalangeal joints.
- In acute attacks of pseudogout, the affected joint is usually erythematous, hot, and acutely tender.
- Pseudogout often involves the wrist and knee, although it may affect almost any joint.
Differentiating Tests
- Arthrocentesis and joint fluid analysis, which shows leukocytes >2000 cells/mm³, and the presence of pyrophosphate crystals.
- Radiographs: chondrocalcinosis; in cases of hemochromatosis, hooklike osteophytes in the second and third metacarpal heads.
Rheumatoid arthritis (RA)
Differentiating Signs/Symptoms
- Number and distribution of the involved joints helps to differentiate RA from OA.
- RA usually causes a symmetric small joint polyarthritis in the hands, particularly affecting the metacarpophalangeal joints and sparing the distal interphalangeal joints. Typically, RA is associated with more prolonged morning stiffness than OA. Patients with acute RA may also feel generally ill, with fatigue and low mood.
- Differentiation is sometimes challenging for hand involvement, and OA and RA can coexist.
Differentiating Tests
- In RA, erythrocyte sedimentation rate and CRP are abnormal and rheumatoid factor and anticyclic citrullinated antibodies are positive. Typical RA erosive changes are seen on x-ray, MRI, or ultrasound.
Psoriatic arthritis
Differentiating Signs/Symptoms
- Psoriatic arthritis can occur in the absence of skin psoriasis and often affects the distal interphalangeal (DIP) joints.
- In psoriatic arthritis, the joint involvement is usually asymmetric, but inflammatory OA can be difficult to distinguish from certain cases of psoriatic arthritis with only DIP involvement.
Differentiating Tests
- In psoriatic arthritis, x-ray might show typical erosive changes. Ultrasound and MRI are usually more sensitive in showing enthesitis, tenosynovitis, and erosions.
Differentiating Signs/Symptoms
- This is common in the hip and knee joints.
- The onset is subacute and there is usually a risk factor such as corticosteroid use. Early on, the joint exam is unremarkable, except for possible localized bony tenderness in the knee.
Differentiating Tests
- MRI is the most sensitive test for AVN. In the early stages, localized subchondral edema is characteristic. In 50% of all cases, accompanying joint effusion may be found. Due to necrosis of the cells of bone marrow and bone fibrovascular tissue, reactions with hyperemia can be delineated.[85]
Internal derangements (e.g., meniscal tears)
Differentiating Signs/Symptoms
- The onset of meniscal tears is usually acute and debilitating, with preceding trauma, although the trauma can be minor.
- Patients may describe true locking (normal flexion, but an inability to extend the affected knee).
Differentiating Tests
- MRI is sensitive in detecting both acute meniscal and cruciate ligament tears, although degenerative meniscal tears are common in OA.
Criteria
- Knee pain plus at least 5 of the following 9 criteria: age >50 years; stiffness <30 minutes; crepitus; bony tenderness; bony enlargement; no palpable warmth; erythrocyte sedimentation rate (ESR) <40 mm/hour; rheumatoid factor <1.40; synovial fluid signs of OA.
- Knee pain plus osteophytes, plus at least 1 of the following 3 criteria: age >50 years; stiffness <30 minutes; crepitus.
- Hard tissue enlargement involving at least 2 of 10 selected joints, swelling in <3 metacarpophalangeal (MCP) joints, and hard tissue enlargement of at least 2 distal interphalangeal (DIP) joints.
- If the patient has <2 enlarged DIP joints, then deformity of at least 1 of the 10 selected joints is necessary in order to classify the symptoms as being due to OA.
- Hip pain is present plus either 1) hip internal rotation ≥15°; pain present on internal rotation of the hip; morning stiffness of the hip for ≤60 minutes; age >50 years, or 2) hip internal rotation <15°; ESR ≤45 mm/hour. If no ESR was obtained, hip flexion ≤115° is substituted (sensitivity 86%, specificity 75%).
- Hip pain plus 2 of the following 3 radiographic criteria: osteophytes (femoral or acetabular); joint space narrowing (superior, axial, and/or medial); ESR <20 mm/hour (sensitivity 89%, specificity 91%).
Treatment Approach
Nonpharmacologic approaches
- Cane use for patients with knee and/or hip OA in one or more joints, which is causing a sufficiently large impact on ambulation, joint stability, or pain to warrant their use
- Tibiofemoral knee braces for patients with OA of the knee, in one or both knees, which is causing a sufficiently large impact on ambulation, joint stability, or pain to warrant their use
- Hand orthoses for patients with OA of the first carpometacarpal (CMC) joint, or in joints apart from the first CMC joint of the hand
- Patellofemoral braces for patients with patellofemoral knee OA.
- Walking aids, such as canes, for people with lower limb OA
- Insoles, braces, tape, splints, or supports are not routinely recommended to OA patients, unless
- there is joint instability or abnormal biomechanical loading AND
- therapeutic exercise is ineffective or unsuitable without the addition of an aid or device AND
- the addition of an aid or device is likely to improve movement.
Pharmacologic treatment
Oral analgesia
Acute exacerbation of symptoms despite regular analgesia
Surgery
Treatment Options
joint pain: medical management
topical analgesia
Primary Options
- capsaicin topical
(0.025 to 0.075%) apply to the affected area(s) three to four times daily when required
- capsaicin topical
- diclofenac topical
(1% gel) upper extremity joints: apply 2 g to the affected area(s) four times daily, maximum 8 g/joint/day up to 32 g/day total; (1% gel) lower extremity joints: apply 4 g to the affected area(s) four times daily, maximum 16 g/joint/day up to 32 g/day total; (1.5% solution) knee joints: apply 40 drops to each affected knee four times daily; (2% solution) knee joints: apply 40 mg (2 sprays) to each affected knee twice daily
- diclofenac topical
- diclofenac epolamine topical
(1.3% patch) apply one patch to the affected area twice daily
- diclofenac epolamine topical
methylsalicylate topical
apply to the affected area(s) three to four times daily when required
Comments
- Topical nonsteroidal anti-inflammatory drugs (NSAIDs) are recommended for patients with OA of the hand or knee, and can be considered for other affected joints.[7] [73] Other topical analgesics include capsaicin and methylsalicylate.[7] The ACR recommends topical capsaicin for patients with OA of the knee, but not for patients with OA of the hand.[7]
- Topical NSAIDs effectively relieve pain in adults with knee or hand OA within 2 weeks of daily application. The results of systematic reviews and meta-analyses report that topical NSAIDs are the most effective topical analgesic for pain relief for OA patients compared with oral NSAIDs, cyclo-oxygenase-2 [COX-2] inhibitors, and opioids, and that diclofenac transdermal patches may be the most effective and safest topical NSAID for pain relief.[146] [147]
- One Cochrane review found that arnica gel may improve symptoms as effectively as a topical NSAID, but with a potentially worse adverse effect profile.[152] In the same review, capsicum-extract gel (capsaicinoids ≤0.05%) did not significantly improve pain or function compared with placebo.[152] However, results of a network meta-analysis suggest that topical capsaicin may be as effective as topical NSAIDs at reducing pain in patients with OA.[153]
nonpharmacologic approaches
Comments
- All patients should start treatment for OA with nonpharmacologic approaches.[134] [136] These include patient education, self-management, exercise programs (with reassurance that exercise, e.g., resistance training, tai chi, yoga, and water-based exercise, is not harmful to the joints), and they may also benefit from cognitive behavioral therapy in combination with physical therapy.[7] [73] [91] [92] [93] [95] [94] [96] [97]
- Exercise is recommended for all patients with OA, though there is considerably more evidence for the use of exercise in the treatment of knee and hip OA than for hand OA.[7] Balance exercises or tai chi are recommended for patients with OA of the knee and/or hip, and yoga is suggested as an alternative for patients with OA of the knee.[7]
- Weight loss is recommended for patients with OA of the knee and/or hip who are overweight.[7]
- Two Cochrane reviews conclude that exercise programs have a small to moderate beneficial effect on pain and function for patients with knee and hip OA.[102] [103] However, the benefit from physical therapy on hip OA is unclear.[104] One meta-analysis showed a modest effect on pain, though no improvement in self-reported function for exercise in patients with OA of the hip.[105] Further meta-analyses reported that 14% more patients with hip OA responded to exercise therapy compared with placebo, and that hip abductor muscle strengthening exercises as significantly improved knee pain and other functional outcomes for patients with knee OA.[106] [107]
- Evidence from randomized controlled trials (RCTs) suggests that quadricep strengthening exercises and weight loss are effective in controlling the pain of knee OA.[108] [109] Subsequent meta-analyses demonstrate that hip strengthening exercises are an effective rehabilitation treatment for patients with OA of the knee.[110] [107] [111]
- Exercise can improve quality of life by reducing pain and increasing function for patients with OA, especially those who are overweight or obese.[112] A combination of diet and exercise has been shown to reduce pain and increase muscle mass in patients with OA, and that diet alone or in combination with exercise can improve function.[113] [114]
- The American College of Rheumatology (ACR) recommends cane use for patients with knee and/or hip OA in one or more joints, which is causing a sufficiently large impact on ambulation, joint stability, or pain to warrant their use; tibiofemoral knee braces for patients with OA of the knee, in one or both knees, which is causing a sufficiently large impact on ambulation, joint stability, or pain to warrant their use; hand orthoses for patients with OA of the first carpometacarpal (CMC) joint, or in joints apart from the first CMC joint of the hand; patellofemoral braces for patients with patellofemoral knee OA.[7]
- The ACR does not recommend modified shoes, or lateral and medial wedged insoles for patients with knee and/or hip OA.[7]
- The National Institute of Health and Care Excellence (NICE) in the UK recommends walking aids, such as canes, for people with lower limb OA; insoles, braces, tape, splints, or supports are not routinely recommended to patients with OA, unless there is joint instability or abnormal biomechanical loading AND therapeutic exercise is ineffective or unsuitable without the addition of an aid or device AND the addition of an aid or device is likely to improve movement.[73]
- One network meta-analysis reported that lateral wedge insoles in combination with knee bracing reduce peak knee adduction moment in patients with tibiofemoral OA, while gait training influenced both knee adduction angular impulse and knee adduction moment, so it is recommended for reducing biomechanical risk factors.[115]
- There is conflicting evidence for the use of orthoses and/or braces for medial knee OA. There is evidence to suggest that lateral wedge insoles do not reduce pain or improve functionality in patients with medial knee OA, but conversely that lateral wedge insoles with arch support significantly improved pain and physical function in patients with knee OA.[116] [117] [118]
- Combining both a knee brace and lateral wedge insoles has been shown to improve pain and function in patients with medial knee OA.[124]
- Unloader shoes do not appear to confer benefit in medial knee OA.[125]
- Patellar bracing or taping for patellofemoral pain can be considered. One RCT suggests the use of a knee brace may be helpful in reducing pain and bone marrow lesions in patellofemoral OA.[126] Results of one meta-analysis reported that a multimodal physical therapy intervention that included taping significantly reduced pain in the short term for patients with patellofemoral OA.[127]
- One meta-analysis found that splinting in patients with thumb and CMC joint OA reduced pain and improved function in the medium term (3-12 months), but not the short term.[128]
- Glucosamine and chondroitin sulfate are not recommended for the management of patients with OA; decisions regarding the use of these agents should be discussed with patients.[7] [73] Despite this recommendation, glucosamine and chondroitin sulfate are commonly used by people with OA. Modest efficacy and low risk may explain the popularity of these supplements among patients.
- Results of studies on the efficacy of glucosamine or chondroitin varies. One meta-analysis found that glucosamine or chondroitin sulfate reduced pain in patients with knee OA individually, but found no additional benefit associated with combination treatment, whereas subsequent evidence suggests that combination treatment is effective for the treatment of knee OA compared with other placebo.[131] The inconsistencies between the labeling and actual contents of many dietary supplements should be considered; prescription-grade preparations should be sought.[134] [136]
- Evidence suggests that acupuncture may benefit patients with knee OA.[137] [138] [139] [219] However, evidence of short-term benefit is based on low- to very-low-quality evidence, and may not be clinically important, when compared with control treatments.[140] One Cochrane review concluded that acupuncture does not appear to reduce pain or improve function relative to sham acupuncture in people with hip OA.[141] However, subsequent meta-analysis suggest that acupuncture is reduced pain and improves function in patients with OA of the knee, and may be used as an adjunctive treatment.[142] [143]
intra-articular corticosteroid injections
Primary Options
- methylprednisolone acetate
4-80 mg intra-articularly as a single dose
- methylprednisolone acetate
- triamcinolone acetonide
2.5 to 40 mg intra-articularly as a single dose
- triamcinolone acetonide
Comments
- Intra-articular corticosteroid injections are useful, particularly in the knee, for acute exacerbations of OA or when nonsteroidal anti-inflammatory drugs are contraindicated or not tolerated, and can be used in addition to the nonpharmacologic therapies and analgesia.
- The ACR recommends intra-articular corticosteroid injections for patients with knee and/or hip OA, but only conditionally recommends this treatment for patients with OA of the hand.[7] In the UK, intra-articular corticosteroid injections are only recommended when other pharmacologic treatments are ineffective or unsuitable, or to support therapeutic exercise.[73]
- Intra-articular corticosteroid injections reduced pain and improved function in patients with OA of the knee at 6 weeks compared with placebo.[189] However, it appears that intra-articular corticosteroid injections do not reduce joint pain for patients with hand or temporomandibular OA compared with placebo.[190] [191]
- It is unclear how long the benefit of intra-articular corticosteroids lasts in patients with OA. Results from meta-analyses vary, with reports of continued efficacy from 1 to 12 weeks in patients with OA of the hip.[187] [188] [192] [193] However, intra-articular corticosteroid may increase the risk of rapidly destructive hip disease, especially at higher doses.[194]
- Meta-analysis of individual patient data suggests that patients with severe knee pain at baseline may derive greater short-term benefit (reduction in pain up to 4 weeks) from intra‐articular corticosteroid injection than patients with less severe pain.[195]
- Intra-articular triamcinolone every 12 weeks for 2 years failed to significantly reduce OA knee pain compared with intra-articular saline (-1.2 vs. -1.9; between-group difference -0.6, 95% CI -1.6 to 0.3) in a double-blind RCT.[196] Triamcinolone was associated with significantly greater cartilage volume loss than saline (mean change in index compartment cartilage thickness of -0.21 mm vs. -0.10 mm; between-group difference -0.11 mm, 95% CI -0.20 to -0.03), but the clinical significance of this finding is unclear.[196]
- Time-limited adverse effects of intra-articular injection include post-injection pain, swelling, and post-injection flare. Intra-articular injection of corticosteroid was not associated with loss of joint space at 1- and 2-year follow-up in a placebo-controlled randomized trial of patients with knee arthritis.[197] Similarly, in meta-analysis intra-articular corticosteroids for knee OA had no effect on joint space narrowing beyond that of control interventions.[187]
- Evidence suggests that recurrent intra-articular corticosteroid injections often provide inferior (or nonsuperior) symptom relief compared with other injectables (including placebo) at 3 months and beyond in patients with OA.[198]
- Dose depends upon size of joint and degree of inflammation present.
acetaminophen + topical analgesia
Primary Options
- acetaminophen
325-1000 mg orally every 6 hours when required, maximum 4000 mg/day
AND
- capsaicin topical
(0.025 to 0.075%) apply to the affected area(s) three to four times daily when required
or
- diclofenac topical
(1% gel) upper extremity joints: apply 2 g to the affected area(s) four times daily, maximum 8 g/joint/day up to 32 g/day total; (1% gel) lower extremity joints: apply 4 g to the affected area(s) four times daily, maximum 16 g/joint/day up to 32 g/day total; (1.5% solution) knee joints: apply 40 drops to each affected knee four times daily; (2% solution) knee joints: apply 40 mg (2 sprays) to each affected knee twice daily
or
- diclofenac epolamine topical
(1.3% patch) apply one patch to the affected area twice daily
or
methylsalicylate topical
apply to the affected area(s) three to four times daily when required
- acetaminophen
Comments
- While topical analgesics should be used as first-line therapy (e.g., capsaicin, nonsteroidal anti-inflammatory drugs [NSAIDs] such as diclofenac, methylsalicylate), acetaminophen could be added if topical therapies alone do not control symptoms.
nonpharmacologic approaches
Comments
- All patients should start treatment for OA with nonpharmacologic approaches.[134] [136] These include patient education, self-management, exercise programs (with reassurance that exercise, e.g., resistance training, tai chi, yoga, and water-based exercise, is not harmful to the joints), and they may also benefit from cognitive behavioral therapy in combination with physical therapy.[7] [73] [91] [92] [93] [95] [94] [96] [97]
- Exercise is recommended for all patients with OA, though there is considerably more evidence for the use of exercise in the treatment of knee and hip OA than for hand OA.[7] Balance exercises or tai chi are recommended for patients with OA of the knee and/or hip, and yoga is suggested as an alternative for patients with OA of the knee.[7]
- Weight loss is recommended for patients with OA of the knee and/or hip who are overweight.[7]
- Two Cochrane reviews conclude that exercise programs have a small to moderate beneficial effect on pain and function for patients with knee and hip OA.[102] [103] However, the benefit from physical therapy on hip OA is unclear.[104] One meta-analysis showed a modest effect on pain, though no improvement in self-reported function for exercise in patients with OA of the hip.[105] Further meta-analyses reported that 14% more patients with hip OA responded to exercise therapy compared with placebo, and that hip abductor muscle strengthening exercises as significantly improved knee pain and other functional outcomes for patients with knee OA.[106] [107]
- Evidence from randomized controlled trials (RCTs) suggests that quadricep strengthening exercises and weight loss are effective in controlling the pain of knee OA.[108] [109] Subsequent meta-analyses demonstrate that hip strengthening exercises are an effective rehabilitation treatment for patients with OA of the knee.[110] [107] [111]
- Exercise can improve quality of life by reducing pain and increasing function for patients with OA, especially those who are overweight or obese.[112] A combination of diet and exercise has been shown to reduce pain and increase muscle mass in patients with OA, and that diet alone or in combination with exercise can improve function.[113] [114]
- The American College of Rheumatology (ACR) recommends cane use for patients with knee and/or hip OA in one or more joints, which is causing a sufficiently large impact on ambulation, joint stability, or pain to warrant their use; tibiofemoral knee braces for patients with OA of the knee, in one or both knees, which is causing a sufficiently large impact on ambulation, joint stability, or pain to warrant their use; hand orthoses for patients with OA of the first carpometacarpal (CMC) joint, or in joints apart from the first CMC joint of the hand; patellofemoral braces for patients with patellofemoral knee OA.[7]
- The ACR does not recommend modified shoes, or lateral and medial wedged insoles for patients with knee and/or hip OA.[7]
- The National Institute of Health and Care Excellence (NICE) in the UK recommends walking aids, such as canes, for people with lower limb OA; insoles, braces, tape, splints, or supports are not routinely recommended to patients with OA, unless there is joint instability or abnormal biomechanical loading AND therapeutic exercise is ineffective or unsuitable without the addition of an aid or device AND the addition of an aid or device is likely to improve movement.[73]
- One network meta-analysis reported that lateral wedge insoles in combination with knee bracing reduce peak knee adduction moment in patients with tibiofemoral OA, while gait training influenced both knee adduction angular impulse and knee adduction moment, so it is recommended for reducing biomechanical risk factors.[115]
- There is conflicting evidence for the use of orthoses and/or braces for medial knee OA. There is evidence to suggest that lateral wedge insoles do not reduce pain or improve functionality in patients with medial knee OA, but conversely that lateral wedge insoles with arch support significantly improved pain and physical function in patients with knee OA.[116] [117] [118]
- Combining both a knee brace and lateral wedge insoles has been shown to improve pain and function in patients with medial knee OA.[124]
- Unloader shoes do not appear to confer benefit in medial knee OA.[125]
- Patellar bracing or taping for patellofemoral pain can be considered. One RCT suggests the use of a knee brace may be helpful in reducing pain and bone marrow lesions in patellofemoral OA.[126] Results of one meta-analysis reported that a multimodal physical therapy intervention that included taping significantly reduced pain in the short term for patients with patellofemoral OA.[127]
- One meta-analysis found that splinting in patients with thumb and CMC joint OA reduced pain and improved function in the medium term (3-12 months), but not the short term.[128]
- Glucosamine and chondroitin sulfate are not recommended for the management of patients with OA; decisions regarding the use of these agents should be discussed with patients.[7] [73] Despite this recommendation, glucosamine and chondroitin sulfate are commonly used by people with OA. Modest efficacy and low risk may explain the popularity of these supplements among patients.
- Results of studies on the efficacy of glucosamine or chondroitin varies. One meta-analysis found that glucosamine or chondroitin sulfate reduced pain in patients with knee OA individually, but found no additional benefit associated with combination treatment, whereas subsequent evidence suggests that combination treatment is effective for the treatment of knee OA compared with other placebo.[131] The inconsistencies between the labeling and actual contents of many dietary supplements should be considered; prescription-grade preparations should be sought.[134] [136]
- Evidence suggests that acupuncture may benefit patients with knee OA.[137] [138] [139] [219] However, evidence of short-term benefit is based on low- to very-low-quality evidence, and may not be clinically important, when compared with control treatments.[140] One Cochrane review concluded that acupuncture does not appear to reduce pain or improve function relative to sham acupuncture in people with hip OA.[141] However, subsequent meta-analysis suggest that acupuncture is reduced pain and improves function in patients with OA of the knee, and may be used as an adjunctive treatment.[142] [143]
intra-articular corticosteroid injections
Primary Options
- methylprednisolone acetate
4-80 mg intra-articularly as a single dose
- methylprednisolone acetate
- triamcinolone acetonide
2.5 to 40 mg intra-articularly as a single dose
- triamcinolone acetonide
Comments
- Intra-articular corticosteroid injections are useful, particularly in the knee, for acute exacerbations of OA or when nonsteroidal anti-inflammatory drugs are contraindicated or not tolerated, and can be used in addition to the nonpharmacologic therapies and analgesia.
- The ACR recommends intra-articular corticosteroid injections for patients with knee and/or hip OA, but only conditionally recommends this treatment for patients with OA of the hand.[7] In the UK, intra-articular corticosteroid injections are only recommended when other pharmacologic treatments are ineffective or unsuitable, or to support therapeutic exercise.[73]
- Intra-articular corticosteroid injections reduced pain and improved function in patients with OA of the knee at 6 weeks compared with placebo.[189] However, it appears that intra-articular corticosteroid injections do not reduce joint pain for patients with hand or temporomandibular OA compared with placebo.[190] [191]
- It is unclear how long the benefit of intra-articular corticosteroids lasts in patients with OA. Results from meta-analyses vary, with reports of continued efficacy from 1 to 12 weeks in patients with OA of the hip.[187] [188] [192] [193] However, intra-articular corticosteroid may increase the risk of rapidly destructive hip disease, especially at higher doses.[194]
- Meta-analysis of individual patient data suggests that patients with severe knee pain at baseline may derive greater short-term benefit (reduction in pain up to 4 weeks) from intra‐articular corticosteroid injection than patients with less severe pain.[195]
- Intra-articular triamcinolone every 12 weeks for 2 years failed to significantly reduce OA knee pain compared with intra-articular saline (-1.2 vs. -1.9; between-group difference -0.6, 95% CI -1.6 to 0.3) in a double-blind RCT.[196] Triamcinolone was associated with significantly greater cartilage volume loss than saline (mean change in index compartment cartilage thickness of -0.21 mm vs. -0.10 mm; between-group difference -0.11 mm, 95% CI -0.20 to -0.03), but the clinical significance of this finding is unclear.[196]
- Time-limited adverse effects of intra-articular injection include post-injection pain, swelling, and post-injection flare. Intra-articular injection of corticosteroid was not associated with loss of joint space at 1- and 2-year follow-up in a placebo-controlled randomized trial of patients with knee arthritis.[197] Similarly, in meta-analysis intra-articular corticosteroids for knee OA had no effect on joint space narrowing beyond that of control interventions.[187]
- Evidence suggests that recurrent intra-articular corticosteroid injections often provide inferior (or nonsuperior) symptom relief compared with other injectables (including placebo) at 3 months and beyond in patients with OA.[198]
- Dose depends upon size of joint and degree of inflammation present.
-
NSAID + acetaminophen + topical capsaicin
Primary Options
- acetaminophen
325-1000 mg orally every 6 hours when required, maximum 4000 mg/day
AND
- capsaicin topical
(0.025 to 0.075%) apply to the affected area(s) three to four times daily when required
AND
- naproxen
250-500 mg orally twice daily when required, maximum 1250 mg/day
or
- ibuprofen
400-800 mg orally every 6-8 hours when required, maximum 3200 mg/day
or
- diclofenac potassium
50 mg orally (immediate-release) twice or three times daily when required
or
- diclofenac sodium
100 mg orally (extended-release) once daily when required
- acetaminophen
Secondary Options
- acetaminophen
325-1000 mg orally every 6 hours when required, maximum 4000 mg/day
AND
- capsaicin topical
(0.025 to 0.075%) apply to the affected area(s) three to four times daily when required
AND
- celecoxib
200 mg orally once daily; or 100 mg orally twice daily
or
- meloxicam
7.5 to 15 mg orally once daily
- acetaminophen
Comments
- Oral nonsteroidal anti-inflammatory drugs (NSAIDs) can be added to acetaminophen and topical analgesics (e.g., capsaicin), to reduce pain and improve function.
- Selective COX-2 inhibitors may be used as an alternative to nonselective NSAIDs. They are associated with reduced risk of GI adverse effects compared with nonselective NSAIDs, but similar renal toxicity.[164] [165] COX-2 inhibitors are effective for the management of pain associated with knee and hip OA, and may have a role in patients at increased risk for GI adverse effects.[136] [156] However, COX-2 inhibitors do not confer an advantage with respect to GI symptoms when compared with placebo, or NSAID and proton-pump inhibitor (PPI) used concomitantly for gastroprotection.[73] [166] [167] The incidence of upper GI adverse effects did not differ between patients with knee OA who were treated with fixed-dose combination naproxen and esomeprazole or with celecoxib; the former reported significantly more heartburn-free days than those on celecoxib.[168]
- Evidence suggests that NSAID use substantially contributes to the association between OA and cardiovascular disease (CVD), with increased risk reaching significance as early as 4 weeks into treatment.[169] [170] Several patient characteristics may be associated with increased CVD risk when taking an NSAID, such as age >80 years, history of CVD, rheumatoid arthritis, chronic obstructive pulmonary disease, renal disease, and hypertension.[171] One meta-analysis suggested that diclofenac and ibuprofen were associated with increased cardiovascular risk while naproxen and celecoxib were not.[172] However, similar incident rates of cardiovascular events have been reported for ibuprofen, celecoxib, and naproxen.[173]
- GI and cardiovascular safety profiles of individual oral NSAIDs differ, and careful patient selection is required to maximize the risk:benefit ratio.[136] The lowest effective dose of NSAID should be used to minimize adverse effects.
nonpharmacologic approaches
Comments
- All patients should start treatment for OA with nonpharmacologic approaches.[134] [136] These include patient education, self-management, exercise programs (with reassurance that exercise, e.g., resistance training, tai chi, yoga, and water-based exercise, is not harmful to the joints), and they may also benefit from cognitive behavioral therapy in combination with physical therapy.[7] [73] [91] [92] [93] [95] [94] [96] [97]
- Exercise is recommended for all patients with OA, though there is considerably more evidence for the use of exercise in the treatment of knee and hip OA than for hand OA.[7] Balance exercises or tai chi are recommended for patients with OA of the knee and/or hip, and yoga is suggested as an alternative for patients with OA of the knee.[7]
- Weight loss is recommended for patients with OA of the knee and/or hip who are overweight.[7]
- Two Cochrane reviews conclude that exercise programs have a small to moderate beneficial effect on pain and function for patients with knee and hip OA.[102] [103] However, the benefit from physical therapy on hip OA is unclear.[104] One meta-analysis showed a modest effect on pain, though no improvement in self-reported function for exercise in patients with OA of the hip.[105] Further meta-analyses reported that 14% more patients with hip OA responded to exercise therapy compared with placebo, and that hip abductor muscle strengthening exercises as significantly improved knee pain and other functional outcomes for patients with knee OA.[106] [107]
- Evidence from randomized controlled trials (RCTs) suggests that quadricep strengthening exercises and weight loss are effective in controlling the pain of knee OA.[108] [109] Subsequent meta-analyses demonstrate that hip strengthening exercises are an effective rehabilitation treatment for patients with OA of the knee.[110] [107] [111]
- Exercise can improve quality of life by reducing pain and increasing function for patients with OA, especially those who are overweight or obese.[112] A combination of diet and exercise has been shown to reduce pain and increase muscle mass in patients with OA, and that diet alone or in combination with exercise can improve function.[113] [114]
- The American College of Rheumatology (ACR) recommends cane use for patients with knee and/or hip OA in one or more joints, which is causing a sufficiently large impact on ambulation, joint stability, or pain to warrant their use; tibiofemoral knee braces for patients with OA of the knee, in one or both knees, which is causing a sufficiently large impact on ambulation, joint stability, or pain to warrant their use; hand orthoses for patients with OA of the first carpometacarpal (CMC) joint, or in joints apart from the first CMC joint of the hand; patellofemoral braces for patients with patellofemoral knee OA.[7]
- The ACR does not recommend modified shoes, or lateral and medial wedged insoles for patients with knee and/or hip OA.[7]
- The National Institute of Health and Care Excellence (NICE) in the UK recommends walking aids, such as canes, for people with lower limb OA; insoles, braces, tape, splints, or supports are not routinely recommended to patients with OA, unless there is joint instability or abnormal biomechanical loading AND therapeutic exercise is ineffective or unsuitable without the addition of an aid or device AND the addition of an aid or device is likely to improve movement.[73]
- One network meta-analysis reported that lateral wedge insoles in combination with knee bracing reduce peak knee adduction moment in patients with tibiofemoral OA, while gait training influenced both knee adduction angular impulse and knee adduction moment, so it is recommended for reducing biomechanical risk factors.[115]
- There is conflicting evidence for the use of orthoses and/or braces for medial knee OA. There is evidence to suggest that lateral wedge insoles do not reduce pain or improve functionality in patients with medial knee OA, but conversely that lateral wedge insoles with arch support significantly improved pain and physical function in patients with knee OA.[116] [117] [118]
- Combining both a knee brace and lateral wedge insoles has been shown to improve pain and function in patients with medial knee OA.[124]
- Unloader shoes do not appear to confer benefit in medial knee OA.[125]
- Patellar bracing or taping for patellofemoral pain can be considered. One RCT suggests the use of a knee brace may be helpful in reducing pain and bone marrow lesions in patellofemoral OA.[126] Results of one meta-analysis reported that a multimodal physical therapy intervention that included taping significantly reduced pain in the short term for patients with patellofemoral OA.[127]
- One meta-analysis found that splinting in patients with thumb and CMC joint OA reduced pain and improved function in the medium term (3-12 months), but not the short term.[128]
- Glucosamine and chondroitin sulfate are not recommended for the management of patients with OA; decisions regarding the use of these agents should be discussed with patients.[7] [73] Despite this recommendation, glucosamine and chondroitin sulfate are commonly used by people with OA. Modest efficacy and low risk may explain the popularity of these supplements among patients.
- Results of studies on the efficacy of glucosamine or chondroitin varies. One meta-analysis found that glucosamine or chondroitin sulfate reduced pain in patients with knee OA individually, but found no additional benefit associated with combination treatment, whereas subsequent evidence suggests that combination treatment is effective for the treatment of knee OA compared with other placebo.[131] The inconsistencies between the labeling and actual contents of many dietary supplements should be considered; prescription-grade preparations should be sought.[134] [136]
- Evidence suggests that acupuncture may benefit patients with knee OA.[137] [138] [139] [219] However, evidence of short-term benefit is based on low- to very-low-quality evidence, and may not be clinically important, when compared with control treatments.[140] One Cochrane review concluded that acupuncture does not appear to reduce pain or improve function relative to sham acupuncture in people with hip OA.[141] However, subsequent meta-analysis suggest that acupuncture is reduced pain and improves function in patients with OA of the knee, and may be used as an adjunctive treatment.[142] [143]
gastroprotection
Primary Options
- omeprazole
20 mg orally once daily
- omeprazole
- esomeprazole
20 mg orally once daily
- esomeprazole
- pantoprazole
40 mg orally once daily
- pantoprazole
- rabeprazole
20 mg orally once daily
- rabeprazole
Secondary Options
- misoprostol
100-200 micrograms orally four times daily
- misoprostol
Comments
- Gastroprotection should be offered to patients on long-term NSAID therapy, especially those at risk of GI bleeding.[73] Evidence suggests that proton-pump inhibitors (PPIs) provide better protection against NSAID-induced peptic ulcer disease and gastritis compared with H2 antagonists.[160] Misoprostol is a prostaglandin E1 analog and is another option for gastroprotection, but diarrhea is a common adverse effect, and the drug is less well tolerated than PPIs.[161] [162] [163]
intra-articular corticosteroid injections
Primary Options
- methylprednisolone acetate
4-80 mg intra-articularly as a single dose
- methylprednisolone acetate
- triamcinolone acetonide
2.5 to 40 mg intra-articularly as a single dose
- triamcinolone acetonide
Comments
- Intra-articular corticosteroid injections are useful, particularly in the knee, for acute exacerbations of OA or when nonsteroidal anti-inflammatory drugs are contraindicated or not tolerated, and can be used in addition to the nonpharmacologic therapies and analgesia.
- The ACR recommends intra-articular corticosteroid injections for patients with knee and/or hip OA, but only conditionally recommends this treatment for patients with OA of the hand.[7] In the UK, intra-articular corticosteroid injections are only recommended when other pharmacologic treatments are ineffective or unsuitable, or to support therapeutic exercise.[73]
- Intra-articular corticosteroid injections reduced pain and improved function in patients with OA of the knee at 6 weeks compared with placebo.[189] However, it appears that intra-articular corticosteroid injections do not reduce joint pain for patients with hand or temporomandibular OA compared with placebo.[190] [191]
- It is unclear how long the benefit of intra-articular corticosteroids lasts in patients with OA. Results from meta-analyses vary, with reports of continued efficacy from 1 to 12 weeks in patients with OA of the hip.[187] [188] [192] [193] However, intra-articular corticosteroid may increase the risk of rapidly destructive hip disease, especially at higher doses.[194]
- Meta-analysis of individual patient data suggests that patients with severe knee pain at baseline may derive greater short-term benefit (reduction in pain up to 4 weeks) from intra‐articular corticosteroid injection than patients with less severe pain.[195]
- Intra-articular triamcinolone every 12 weeks for 2 years failed to significantly reduce OA knee pain compared with intra-articular saline (-1.2 vs. -1.9; between-group difference -0.6, 95% CI -1.6 to 0.3) in a double-blind RCT.[196] Triamcinolone was associated with significantly greater cartilage volume loss than saline (mean change in index compartment cartilage thickness of -0.21 mm vs. -0.10 mm; between-group difference -0.11 mm, 95% CI -0.20 to -0.03), but the clinical significance of this finding is unclear.[196]
- Time-limited adverse effects of intra-articular injection include post-injection pain, swelling, and post-injection flare. Intra-articular injection of corticosteroid was not associated with loss of joint space at 1- and 2-year follow-up in a placebo-controlled randomized trial of patients with knee arthritis.[197] Similarly, in meta-analysis intra-articular corticosteroids for knee OA had no effect on joint space narrowing beyond that of control interventions.[187]
- Evidence suggests that recurrent intra-articular corticosteroid injections often provide inferior (or nonsuperior) symptom relief compared with other injectables (including placebo) at 3 months and beyond in patients with OA.[198]
- Dose depends upon size of joint and degree of inflammation present.
-
viscosupplementation with intra-articular hyaluronic acid
Primary Options
- sodium hyaluronate
20 mg (2 mL) intra-articularly once weekly for 3-5 weeks
- sodium hyaluronate
hylan GF 20
16 mg (2 mL) intra-articularly once weekly for 3 weeks, total of 3 injections; 6 mL intra-articularly as single injection
Comments
- One literature review concludes that intra-articular hyaluronic acid should be considered as a treatment for patients with OA, tailored by disease stage and patient phenotype, despite recommendations to the contrary from international guidelines.[202]
- One meta-analysis found that intra-articular viscosupplementation with hyaluronan or hylan derivatives is effective in the management of OA of the knee; improvement from baseline during the 5- to 13-week post-injection period was 28% to 54% for pain and 9% to 32% for function.[201] The analyses suggested that different hyaluronan/hylan products exert differential therapeutic effects, and that response is time dependent.[201]
- Analyzing data only from placebo-controlled trials with low risk of bias, one meta-analysis indicated that intra-articular hyaluronic acid provides a modest, but real, benefit for patients with OA of the knee (pain intensity standardized mean difference [SMD] -0.21, 95% CI -0.32 to -0.10; function at 3 months SMD -0.12, 95% CI -0.22 to -0.02).[203]
opioid + NSAID + acetaminophen + topical capsaicin
Primary Options
- acetaminophen
325-1000 mg orally every 6 hours when required, maximum 4000 mg/day
AND
- capsaicin topical
(0.025 to 0.075%) apply to the affected area(s) three to four times daily when required
AND
- naproxen
250-500 mg orally twice daily when required, maximum 1250 mg/day
or
- ibuprofen
400-800 mg orally every 6-8 hours when required, maximum 3200 mg/day
or
- diclofenac potassium
50 mg orally (immediate-release) twice or three times daily when required
or
- diclofenac sodium
100 mg orally (extended-release) once daily when required
or
- celecoxib
200 mg orally once daily; or 100 mg orally twice daily
or
- meloxicam
7.5 to 15 mg orally once daily
AND
- tramadol
50-100 mg orally (immediate-release) every 4-6 hours when required, maximum 400 mg/day
or
- oxycodone
5-10 mg orally (immediate-release) every 4-6 hours when required; 10 mg orally (controlled-release) twice daily when required
or
- codeine sulfate
15-60 mg orally every 4-6 hours when required, maximum 360 mg/day
or
- morphine sulfate
10-30 mg orally (immediate-release) every 4 hours when required; 15 mg orally (controlled-release) every 8-12 hours when required
- acetaminophen
Comments
- Opioids are reserved for pain relief in patients whose symptoms are inadequately controlled, or in whom the other agents are inadequate or contraindicated.[73]
- Opioids can be added to topical analgesics (e.g., capsaicin), acetaminophen, and nonsteroidal anti-inflammatory drugs (NSAIDs) (or cyclo-oxygenase-2 [COX-2] inhibitors).
- It should be noted that the potential clinical benefit of opioid treatment, regardless of preparation or dose, does not outweigh the harm opioid treatment may cause in patients with OA.[147] Opioids provide minimal relief of OA symptoms, and are known to cause discomfort in a many patients. Clinicians should give careful consideration to the utility of opioids in the management of OA.[174]
- Oral and transdermal opioids can decrease pain intensity and improve function in patients with OA of the knee or hip compared with placebo, but the observed benefits were small (12% absolute improvement in mean pain compared with placebo [various pain scales]; number needed to benefit of 10).[175] No studies of tramadol contributed to these results.
- A subsequent meta-analysis reported that opioids did not demonstrate a clinically relevant reduction in pain or disability compared with placebo in patients with OA of the hip or knee in at 4-24 weeks. Number needed to treat for an additional dropout due to side effects was 5 (95% CI 4 to 7).[176]
- Opioids are used at the smallest possible dose and shortest possible course to avoid adverse effects, especially in older people.
- Patients requiring opioid analgesia are considered for surgery.
duloxetine
Primary Options
- duloxetine
30 mg orally once daily initially, increase according to response, maximum 120 mg/day
- duloxetine
Comments
- Duloxetine is an antidepressant with analgesic properties.
- Results from one systematic review suggest that duloxetine may be effective for the treatment of chronic pain associated with OA, with a number needed to benefit (clinically meaningful outcome at study end compared with placebo) of 7.[179]
- Indirect comparisons between duloxetine and a number of post-first-line oral treatments for OA, including selective COX-2 inhibitors and opioids, found no difference in the total WOMAC composite scores (an inclusive set of OA outcomes) after approximately 12 weeks of treatment.[180] Some analyses suggested that etoricoxib (not available in the US) may be superior to duloxetine.[180]
- Commonly observed adverse effects reported among patients with OA treated with duloxetine include nausea, fatigue, constipation, and dry mouth.[181] There is a possible increased serotonergic effect if given with tramadol.
nonpharmacologic approaches
Comments
- All patients should start treatment for OA with nonpharmacologic approaches.[134] [136] These include patient education, self-management, exercise programs (with reassurance that exercise, e.g., resistance training, tai chi, yoga, and water-based exercise, is not harmful to the joints), and they may also benefit from cognitive behavioural therapy in combination with physical therapy.[7] [73] [91] [92] [93] [95] [94] [96] [97]
- Exercise is recommended for all patients with OA, though there is considerably more evidence for the use of exercise in the treatment of knee and hip OA than for hand OA.[7] Balance exercises or tai chi are recommended for patients with OA of the knee and/or hip, and yoga is suggested as an alternative for patients with OA of the knee.[7]
- Weight loss is recommended for patients with OA of the knee and/or hip who are overweight.[7]
- Two Cochrane reviews conclude that exercise programs have a small to moderate beneficial effect on pain and function for patients with knee and hip OA.[102] [103] However, the benefit from physical therapy on hip OA is unclear.[104] One meta-analysis showed a modest effect on pain, though no improvement in self-reported function for exercise in patients with OA of the hip.[105] Further meta-analyses reported that 14% more patients with hip OA responded to exercise therapy compared with placebo, and that hip abductor muscle strengthening exercises as significantly improved knee pain and other functional outcomes for patients with knee OA.[106] [107]
- Evidence from randomized controlled trials (RCTs) suggests that quadricep strengthening exercises and weight loss are effective in controlling the pain of knee OA.[108] [109] Subsequent meta-analyses demonstrate that hip strengthening exercises are an effective rehabilitation treatment for patients with OA of the knee.[110] [107] [111]
- Exercise can improve quality of life by reducing pain and increasing function for patients with OA, especially those who are overweight or obese.[112] A combination of diet and exercise has been shown to reduce pain and increase muscle mass in patients with OA, and that diet alone or in combination with exercise can improve function.[113] [114]
- The American College of Rheumatology (ACR) recommends cane use for patients with knee and/or hip OA in one or more joints, which is causing a sufficiently large impact on ambulation, joint stability, or pain to warrant their use; tibiofemoral knee braces for patients with OA of the knee, in one or both knees, which is causing a sufficiently large impact on ambulation, joint stability, or pain to warrant their use; hand orthoses for patients with OA of the first carpometacarpal (CMC) joint, or in joints apart from the first CMC joint of the hand; patellofemoral braces for patients with patellofemoral knee OA.[7]
- The ACR does not recommend modified shoes, or lateral and medial wedged insoles for patients with knee and/or hip OA.[7]
- The National Institute of Health and Care Excellence (NICE) in the UK recommends walking aids, such as canes, for people with lower limb OA; insoles, braces, tape, splints, or supports are not routinely recommended to patients with OA, unless there is joint instability or abnormal biomechanical loading AND therapeutic exercise is ineffective or unsuitable without the addition of an aid or device AND the addition of an aid or device is likely to improve movement.[73]
- One network meta-analysis reported that lateral wedge insoles in combination with knee bracing reduce peak knee adduction moment in patients with tibiofemoral OA, while gait training influenced both knee adduction angular impulse and knee adduction moment, so it is recommended for reducing biomechanical risk factors.[115]
- There is conflicting evidence for the use of orthoses and/or braces for medial knee OA. There is evidence to suggest that lateral wedge insoles do not reduce pain or improve functionality in patients with medial knee OA, but conversely that lateral wedge insoles with arch support significantly improved pain and physical function in patients with knee OA.[116] [117] [118]
- Combining both a knee brace and lateral wedge insoles has been shown to improve pain and function in patients with medial knee OA.[124]
- Unloader shoes do not appear to confer benefit in medial knee OA.[125]
- Patellar bracing or taping for patellofemoral pain can be considered. One RCT suggests the use of a knee brace may be helpful in reducing pain and bone marrow lesions in patellofemoral OA.[126] Results of one meta-analysis reported that a multimodal physical therapy intervention that included taping significantly reduced pain in the short term for patients with patellofemoral OA.[127]
- One meta-analysis found that splinting in patients with thumb and CMC joint OA reduced pain and improved function in the medium term (3-12 months), but not the short term.[128]
- Glucosamine and chondroitin sulfate are not recommended for the management of patients with OA; decisions regarding the use of these agents should be discussed with patients.[7] [73] Despite this recommendation, glucosamine and chondroitin sulfate are commonly used by people with OA. Modest efficacy and low risk may explain the popularity of these supplements among patients.
- Results of studies on the efficacy of glucosamine or chondroitin varies. One meta-analysis found that glucosamine or chondroitin sulfate reduced pain in patients with knee OA individually, but found no additional benefit associated with combination treatment, whereas subsequent evidence suggests that combination treatment is effective for the treatment of knee OA compared with other placebo.[131] The inconsistencies between the labeling and actual contents of many dietary supplements should be considered; prescription-grade preparations should be sought.[134] [136]
- Evidence suggests that acupuncture may benefit patients with knee OA.[137] [138] [139] [219] However, evidence of short-term benefit is based on low- to very-low-quality evidence, and may not be clinically important, when compared with control treatments.[140] One Cochrane review concluded that acupuncture does not appear to reduce pain or improve function relative to sham acupuncture in people with hip OA.[141] However, subsequent meta-analysis suggest that acupuncture is reduced pain and improves function in patients with OA of the knee, and may be used as an adjunctive treatment.[142] [143]
gastroprotection
Primary Options
- omeprazole
20 mg orally once daily
- omeprazole
- esomeprazole
20 mg orally once daily
- esomeprazole
- pantoprazole
40 mg orally once daily
- pantoprazole
- rabeprazole
20 mg orally once daily
- rabeprazole
Secondary Options
- misoprostol
100-200 micrograms orally four times daily
- misoprostol
Comments
- Gastroprotection should be offered to patients on long-term NSAID therapy, especially those at risk of GI bleeding.[73] Evidence suggests that proton-pump inhibitors (PPIs) provide better protection against NSAID-induced peptic ulcer disease and gastritis compared with H2 antagonists.[160] Misoprostol is a prostaglandin E1 analog and is another option for gastroprotection, but diarrhea is a common adverse effect, and the drug is less well tolerated than PPIs.[161] [162] [163]
intra-articular corticosteroid injections
Primary Options
- methylprednisolone acetate
4-80 mg intra-articularly as a single dose
- methylprednisolone acetate
- triamcinolone acetonide
2.5 to 40 mg intra-articularly as a single dose
- triamcinolone acetonide
Comments
- Intra-articular corticosteroid injections are useful, particularly in the knee, for acute exacerbations of OA or when nonsteroidal anti-inflammatory drugs are contraindicated or not tolerated, and can be used in addition to the nonpharmacologic therapies and analgesia.
- The ACR recommends intra-articular corticosteroid injections for patients with knee and/or hip OA, but only conditionally recommends this treatment for patients with OA of the hand.[7] In the UK, intra-articular corticosteroid injections are only recommended when other pharmacologic treatments are ineffective or unsuitable, or to support therapeutic exercise.[73]
- Intra-articular corticosteroid injections reduced pain and improved function in patients with OA of the knee at 6 weeks compared with placebo.[189] However, it appears that intra-articular corticosteroid injections do not reduce joint pain for patients with hand or temporomandibular OA compared with placebo.[190] [191]
- It is unclear how long the benefit of intra-articular corticosteroids lasts in patients with OA. Results from meta-analyses vary, with reports of continued efficacy from 1 to 12 weeks in patients with OA of the hip.[187] [188] [192] [193] However, intra-articular corticosteroid may increase the risk of rapidly destructive hip disease, especially at higher doses.[194]
- Meta-analysis of individual patient data suggests that patients with severe knee pain at baseline may derive greater short-term benefit (reduction in pain up to 4 weeks) from intra‐articular corticosteroid injection than patients with less severe pain.[195]
- Intra-articular triamcinolone every 12 weeks for 2 years failed to significantly reduce OA knee pain compared with intra-articular saline (-1.2 vs. -1.9; between-group difference -0.6, 95% CI -1.6 to 0.3) in a double-blind RCT.[196] Triamcinolone was associated with significantly greater cartilage volume loss than saline (mean change in index compartment cartilage thickness of -0.21 mm vs. -0.10 mm; between-group difference -0.11 mm, 95% CI -0.20 to -0.03), but the clinical significance of this finding is unclear.[196]
- Time-limited adverse effects of intra-articular injection include post-injection pain, swelling, and post-injection flare. Intra-articular injection of corticosteroid was not associated with loss of joint space at 1- and 2-year follow-up in a placebo-controlled randomized trial of patients with knee arthritis.[197] Similarly, in meta-analysis intra-articular corticosteroids for knee OA had no effect on joint space narrowing beyond that of control interventions.[187]
- Evidence suggests that recurrent intra-articular corticosteroid injections often provide inferior (or nonsuperior) symptom relief compared with other injectables (including placebo) at 3 months and beyond in patients with OA.[198]
- Dose depends upon size of joint and degree of inflammation present.
-
viscosupplementation with intra-articular hyaluronic acid
Primary Options
- sodium hyaluronate
20 mg (2 mL) intra-articularly once weekly for 3-5 weeks
- sodium hyaluronate
hylan GF 20
16 mg (2 mL) intra-articularly once weekly for 3 weeks, total of 3 injections; 6 mL intra-articularly as single injection
Comments
- One literature review concludes that intra-articular hyaluronic acid should be considered as a treatment for patients with OA, tailored by disease stage and patient phenotype, despite recommendations to the contrary from international guidelines.[202]
- One meta-analysis found that intra-articular viscosupplementation with hyaluronan or hylan derivatives is effective in the management of OA of the knee; improvement from baseline during the 5- to 13-week post-injection period was 28% to 54% for pain and 9% to 32% for function.[201] The analyses suggested that different hyaluronan/hylan products exert differential therapeutic effects, and that response is time dependent.[201]
- Analysing data only from placebo-controlled trials with low risk of bias, one meta-analysis indicated that intra-articular hyaluronic acid provides a modest, but real, benefit for patients with OA of the knee (pain intensity standardized mean difference [SMD] -0.21, 95% CI -0.32 to -0.10; function at 3 months SMD -0.12, 95% CI -0.22 to -0.02).[203]
persistent pain despite multiple treatment modalities or with severe disability
surgery
Comments
- Patients with OA pain that persists despite multiple treatment modalities and which substantially impacts their quality of life should be referred and considered for joint placement surgery.[73]
- Total knee replacement followed by nonsurgical treatment resulted in significantly greater pain relief and functional improvement after 12 months than nonsurgical treatment alone (Knee Injury and Osteoarthritis Outcome Score [KOOS4] 32.5 vs. 16.0; adjusted mean difference 15.8, 95% CI 10.0 to 21.5) in a randomized controlled trial of patients with moderate-to-severe knee OA who were eligible for unilateral total knee replacement.[205] Total knee replacement was associated with more serious adverse events.[205]
- Unipartmental (partial) knee arthroplasty has been demonstrated to provides pain relief and satisfactory activity level for patients ages 60 years or younger. The results of one meta-analysis reported that 96.5% of implants survived at 10-year follow-up.[206]
- There is no role of partial meniscectomy for meniscal tear in knee OA based on a randomized controlled trial.[207]
- Arthroscopic surgery is not effective for knee OA.[33] [208] [209] Clinical guidelines do not recommend the use of arthroscopic surgery in knee OA.[7] [73] BMJ Rapid Recommendations: arthroscopic surgery for degenerative knee arthritis and meniscal tears MAGICapp: recommendations, evidence summaries and consultation decision aids
- In patients with primary glenohumeral OA with an intact rotator cuff, total shoulder arthroplasty significantly improved postoperative patient-reported outcome measures (PROMs) compared with hemiarthroplasty.[210]
- Arthroplasty, trapeziectomy, and arthrodesis are options for thumb OA.[213] One meta-analysis concluded that there remains uncertainty about which procedure offers the best functional outcome and safety profile to treat OA of the thumb, the results of the systematic review suggest trapeziectomy with ligament reconstruction and tendon interposition yielded good postoperative range of movement, while arthrodesis demonstrated a high rate of moderate-severe complications.[214]
topical and oral analgesia
Primary Options
- acetaminophen
325-1000 mg orally every 6 hours when required, maximum 4000 mg/day
AND
- capsaicin topical
(0.025 to 0.075%) apply to the affected area(s) three to four times daily when required
AND
- naproxen
250-500 mg orally twice daily when required, maximum 1250 mg/day
or
- ibuprofen
400-800 mg orally every 6-8 hours when required, maximum 3200 mg/day
or
- diclofenac potassium
50 mg orally (immediate-release) twice or three times daily when required
or
- diclofenac sodium
100 mg orally (extended-release) once daily when required
or
- celecoxib
200 mg orally once daily; or 100 mg orally twice daily
or
- meloxicam
7.5 to 15 mg orally once daily
AND
- tramadol
50-100 mg orally (immediate-release) every 4-6 hours when required, maximum 400 mg/day
or
- oxycodone
5-10 mg orally (immediate-release) every 4-6 hours when required; 10 mg orally (controlled-release) twice daily when required
or
- codeine sulfate
15-60 mg orally every 4-6 hours when required, maximum 360 mg/day
or
- morphine sulfate
10-30 mg orally (immediate-release) every 4 hours when required; 15 mg orally (controlled-release) every 8-12 hours when required
- acetaminophen
Comments
- Topical and oral analgesia should be continued as required while awaiting joint replacement and can be used in combination.
- Studies have demonstrated that acetaminophen has a small to modest benefit for patients with OA of the hip or knee, and is statistically inferior to all other drug categories for the management of OA pain (oral NSAIDs, topical NSAIDs, COX-2 inhibitors, and opioids).[154] [146] [155] As such acetaminophen alone may not have a role in the treatment of hip or knee OA, irrespective of the dose used, but may be added for rescue analgesia, or if local therapies alone do not control symptoms.[136] [156]
- Selective COX-2 inhibitors may be used as an alternative to nonselective NSAIDs. They are associated with reduced risk of GI adverse effects compared with nonselective NSAIDs, but similar renal toxicity.[164] [165] COX-2 inhibitors are effective for the management of pain associated with knee and hip OA, and may have a role in patients at increased risk for GI adverse effects.[136] [156] However, COX-2 inhibitors do not confer an advantage with respect to GI symptoms when compared with placebo, or NSAID and proton-pump inhibitor (PPI) used concomitantly for gastroprotection.[73] [166] [167] The incidence of upper GI adverse effects did not differ between patients with knee OA who were treated with fixed-dose combination naproxen and esomeprazole or with celecoxib; the former reported significantly more heartburn-free days than those on celecoxib.[168]
- Evidence suggests that NSAID use substantially contributes to the association between OA and cardiovascular disease (CVD), with increased risk reaching significance as early as 4 weeks into treatment.[169] [170] Several patient characteristics may be associated with increased CVD risk when taking an NSAID, such as age >80 years, history of CVD, rheumatoid arthritis, chronic obstructive pulmonary disease, renal disease, and hypertension.[171] One meta-analysis suggested that diclofenac and ibuprofen were associated with increased cardiovascular risk, while naproxen and celecoxib were not.[172] However, similar incident rates of cardiovascular events have been reported for ibuprofen, celecoxib, and naproxen.[173]
- GI and cardiovascular safety profiles of individual oral NSAIDs differ, and careful patient selection is required to maximize the risk:benefit ratio.[136] The lowest effective dose of NSAID should be used to minimize adverse effects.
- It should be noted that the potential clinical benefit of opioid treatment, regardless of preparation or dose, does not outweigh the harm opioid treatment may cause in patients with OA.[147] Opioids provide minimal relief of OA symptoms, and are known to cause discomfort in a many patients. Clinicians should give careful consideration to the utility of opioids in the management of OA.[174]
- Oral and transdermal opioids can decrease pain intensity and improve function in patients with OA of the knee or hip compared with placebo, but the observed benefits were small (12% absolute improvement in mean pain compared with placebo [various pain scales]; number needed to benefit of 10).[175] No studies of tramadol contributed to these results.
- A subsequent meta-analysis reported that opioids did not demonstrate a clinically relevant reduction in pain or disability compared with placebo in patients with OA of the hip or knee in at 4-24 weeks. Number needed to treat for an additional dropout due to side effects was 5 (95% CI 4 to 7).[176]
duloxetine
Primary Options
- duloxetine
30 mg orally once daily initially, increase according to response, maximum 120 mg/day
- duloxetine
Comments
- May be continued while awaiting joint replacement.
- Duloxetine inhibits the reuptake of both serotonin and norepinephrine and can be used to reduce pain and improve function.
- Results from one systematic review suggest that duloxetine may be effective for the treatment of chronic pain associated with OA, with a number needed to benefit (clinically meaningful outcome at study end compared with placebo) of 7.[179]
- Indirect comparisons between duloxetine and a number of post-first-line oral treatments for OA, including selective COX-2 inhibitors and opioids, found no difference in the total WOMAC composite scores (an inclusive set of OA outcomes) after approximately 12 weeks of treatment.[180] Some analyses suggested that etoricoxib (not available in the US) may be superior to duloxetine.[180]
- Commonly observed adverse effects reported among patients with OA treated with duloxetine include nausea, fatigue, constipation, and dry mouth.[181] There is a possible increased serotonergic effect if given with tramadol.
gastroprotection
Primary Options
- omeprazole
20 mg orally once daily
- omeprazole
- esomeprazole
20 mg orally once daily
- esomeprazole
- pantoprazole
40 mg orally once daily
- pantoprazole
- rabeprazole
20 mg orally once daily
- rabeprazole
Secondary Options
- misoprostol
100-200 micrograms orally four times daily
- misoprostol
Comments
- Gastroprotection should be offered to patients on long-term NSAID therapy, especially those at risk of GI bleeding.[73] Evidence suggests that proton-pump inhibitors (PPIs) provide better protection against NSAID-induced peptic ulcer disease and gastritis compared with H2 antagonists.[160] Misoprostol is a prostaglandin E1 analog and is another option for gastroprotection, but diarrhea is a common adverse effect, and the drug is less well tolerated than PPIs.[161] [162] [163]
viscosupplementation with intra-articular hyaluronic acid
Primary Options
- sodium hyaluronate
20 mg (2 mL) intra-articularly once weekly for 3-5 weeks
- sodium hyaluronate
hylan GF 20
16 mg (2 mL) intra-articularly once weekly for 3 weeks, total of 3 injections; 6 mL intra-articularly as single injection
Comments
- May be continued while awaiting joint replacement.
- One literature review concludes that intra-articular hyaluronic acid should be considered as a treatment for patients with OA, tailored by disease stage and patient phenotype, despite recommendations to the contrary from international guidelines.[202]
- One meta-analysis found that intra-articular viscosupplementation with hyaluronan or hylan derivatives is effective in the management of OA of the knee; improvement from baseline during the 5- to 13-week post-injection period was 28% to 54% for pain and 9% to 32% for function.[201] The analyses suggested that different hyaluronan/hylan products exert differential therapeutic effects, and that response is time dependent.[201]
- Analysing data only from placebo-controlled trials with low risk of bias, one meta-analysis indicated that intra-articular hyaluronic acid provides a modest, but real, benefit for patients with OA of the knee (pain intensity standardized mean difference [SMD] -0.21, 95% CI -0.32 to -0.10; function at 3 months SMD -0.12, 95% CI -0.22 to -0.02).[203]
-
intra-articular corticosteroid injections
Primary Options
- methylprednisolone acetate
4-80 mg intra-articularly as a single dose
- methylprednisolone acetate
- triamcinolone acetonide
2.5 to 40 mg intra-articularly as a single dose
- triamcinolone acetonide
Comments
- May be continued while awaiting joint replacement.
- Intra-articular corticosteroid injections are useful, particularly in the knee, for acute exacerbations of OA or when nonsteroidal anti-inflammatory drugs are contraindicated or not tolerated, and can be used in addition to the nonpharmacologic therapies and analgesia.
- The ACR recommends intra-articular corticosteroid injections for patients with knee and/or hip OA, but only conditionally recommends this treatment for patients with OA of the hand.[7] In the UK, intra-articular corticosteroid injections are only recommended when other pharmacologic treatments are ineffective or unsuitable, or to support therapeutic exercise.[73]
- Intra-articular corticosteroid injections reduced pain and improved function in patients with OA of the knee at 6 weeks compared with placebo.[189] However, it appears that intra-articular corticosteroid injections do not reduce joint pain for patients with hand or temporomandibular OA compared with placebo.[190] [191]
- It is unclear how long the benefit of intra-articular corticosteroids lasts in patients with OA. Results from meta-analyses vary, with reports of continued efficacy from 1 to 12 weeks in patients with OA of the hip.[187] [188] [192] [193] However, intra-articular corticosteroid may increase the risk of rapidly destructive hip disease, especially at higher doses.[194]
- Meta-analysis of individual patient data suggests that patients with severe knee pain at baseline may derive greater short-term benefit (reduction in pain up to 4 weeks) from intra‐articular corticosteroid injection than patients with less severe pain.[195]
- Intra-articular triamcinolone every 12 weeks for 2 years failed to significantly reduce OA knee pain compared with intra-articular saline (-1.2 vs. -1.9; between-group difference -0.6, 95% CI -1.6 to 0.3) in a double-blind RCT.[196] Triamcinolone was associated with significantly greater cartilage volume loss than saline (mean change in index compartment cartilage thickness of -0.21 mm vs. -0.10 mm; between-group difference -0.11 mm, 95% CI -0.20 to -0.03), but the clinical significance of this finding is unclear.[196]
- Time-limited adverse effects of intra-articular injection include post-injection pain, swelling, and post-injection flare. Intra-articular injection of corticosteroid was not associated with loss of joint space at 1- and 2-year follow-up in a placebo-controlled randomized trial of patients with knee arthritis.[197] Similarly, in meta-analysis intra-articular corticosteroids for knee OA had no effect on joint space narrowing beyond that of control interventions.[187]
- Evidence suggests that recurrent intra-articular corticosteroid injections often provide inferior (or nonsuperior) symptom relief compared with other injectables (including placebo) at 3 months and beyond in patients with OA.[198]
- Dose depends upon size of joint and degree of inflammation present.
Emerging Tx
Extracorporeal shockwave therapy (ESWT)
Autologous conditioned serum (ACS)
Platelet-rich plasma (PRP) intra-articular injections
Radiofrequency ablation
Tapentadol
Ketorolac
Cell-mediated gene therapy
Stem cell therapy
Combined intra-articular injections
Antinerve growth factor antibodies
Prevention
Primary Prevention
- Person-centered interventions to promote education, self-management, and exercises that mitigate known modifiable risk factors for re-injury and nontraumatic OA.
- Education and exercise therapy based rehabilitation for patients with anterior cruciate ligament tear, with optional reconstruction if a patient cannot achieve their acceptable functional level.
- Monitoring knee pain and other symptoms, adverse events, knee-related quality of life and cognitive behavioral factors (fear, self-efficacy, and confidence), self-reported knee function, quadriceps and hamstring muscle function (strength), functional performance (hop battery), and physical activity/sport participation.
Secondary Prevention
Follow-Up Overview
Prognosis
Monitoring
Complications
Citations
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). 2020 Feb;72(2):149-62.[Abstract][Full Text]
National Institute for Health and Care Excellence. Osteoarthritis in over 16s: diagnosis and management. Oct 2022 [internet publication].[Full Text]
Bruyère O, Honvo G, Veronese N, et al. An updated algorithm recommendation for the management of knee osteoarthritis from the European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO). Semin Arthritis Rheum. 2019 Dec;49(3):337-50.[Abstract][Full Text]
1. Sharma L, Kapoor D, Issa S. Epidemiology of osteoarthritis: an update. Curr Opin Rheumatol. 2006;18:147-156.[Abstract]
2. Hunter DJ, Felson DT. Osteoarthritis. BMJ. 2006;332:639-642.[Abstract]
3. Altman R, Asch E, Bloch D, et al; Diagnostic and Therapeutic Criteria Committee of the American Rheumatism Association. Development of criteria for the classification and reporting of osteoarthritis: classification of osteoarthritis of the knee. Arthritis Rheum. 1986;29:1039-49.[Abstract]
4. Altman RD. Criteria for classification of clinical osteoarthritis. J Rheumatol Suppl. 1991 Feb;27:10-2.[Abstract]
5. Kellgren JH, Lawrence JS. Radiological assessment of osteo-arthrosis. Ann Rheum Dis. 1957 Dec;16(4):494-502.[Abstract][Full Text]
6. Schiphof D, Boers M, Bierma-Zeinstra SM. Differences in descriptions of Kellgren and Lawrence grades of knee osteoarthritis. Ann Rheum Dis. 2008 Jul;67(7):1034-6.[Abstract]
7. 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). 2020 Feb;72(2):149-62.[Abstract][Full Text]
8. Cisternas MG, Murphy L, Sacks JJ, et al. Alternative methods for defining osteoarthritis and the impact on estimating prevalence in a US population-based survey. Arthritis Care Res (Hoboken). 2016 May;68(5):574-80.[Abstract][Full Text]
9. Zhang Y, Jordan JM. Epidemiology of osteoarthritis. Clin Geriatr Med. 2010 Aug;26(3):355-69.[Abstract][Full Text]
10. Prieto-Alhambra D, Judge A, Javaid MK, et al. Incidence and risk factors for clinically diagnosed knee, hip and hand osteoarthritis: influences of age, gender and osteoarthritis affecting other joints. Ann Rheum Dis. 2014 Sep;73(9):1659-64.[Abstract][Full Text]
11. van der Oest MJW, Duraku LS, Andrinopoulou ER, et al. The prevalence of radiographic thumb base osteoarthritis: a meta-analysis. Osteoarthr Cartil. 2021 Jun;29(6):785-92.[Abstract][Full Text]
12. Wilson MG, Michel CJ Jr, Ilstrup DM, et al. Idiopathic symptomatic osteoarthritis of the hip and knee: a population-based incidence study. Mayo Clin Proc. 1990; 65:1214-1221.[Abstract]
13. Oliveria SA, Felson DT, Reed JI, et al. Incidence of symptomatic hand, hip, and knee osteoarthritis among patients in a health maintenance organization. Arthritis Rheum. 1995;38:1134-1141.[Abstract]
14. Moss AS, Murphy LB, Helmick CG, et al. Annual incidence rates of hip symptoms and three hip OA outcomes from a U.S. population-based cohort study: the Johnston County Osteoarthritis Project. Osteoarthr Cartil. 2016 Sep;24(9):1518-27.[Abstract][Full Text]
15. Felson DT, Naimark A, Anderson J, et al. The prevalence of knee osteoarthritis in the elderly: the Framingham Osteoarthritis Study. Arthritis Rheum. 1987;30:914-918.[Abstract]
16. Felson DT, Zhang Y, Hannan MT, et al. The incidence and natural history of knee osteoarthritis in the elderly. The Framingham Osteoarthritis Study. Arthritis Rheum. 1995;38:1500-1505.[Abstract]
17. Kim C, Linsenmeyer KD, Vlad SC, et al. Prevalence of radiographic and symptomatic hip osteoarthritis in an urban United States community: the Framingham osteoarthritis study. Arthritis Rheumatol. 2014 Nov;66(11):3013-7.[Abstract][Full Text]
18. Nevitt MC, Xu L, Zhang Y, et al. Very low prevalence of hip osteoarthritis among Chinese elderly in Beijing, China, compared with whites in the United States: the Beijing osteoarthritis study. Arthritis Rheum. 2002;46:1773-1779.[Abstract]
19. Zhang Y, Xu L, Nevitt MC, et al. Comparison of the prevalence of knee osteoarthritis between the elderly Chinese population in Beijing and whites in the United States: the Beijing Osteoarthritis Study. Arthritis Rheum. 2001;44:2065-2071.[Abstract]
20. Fan Z, Yan L, Liu H, et al. The prevalence of hip osteoarthritis: a systematic review and meta-analysis. Arthritis Res Ther. 2023 Mar 29;25(1):51.[Abstract][Full Text]
21. Glyn-Jones S, Palmer AJ, Agricola R, et al. Osteoarthritis. Lancet. 2015 Jul 25;386(9991):376-87.[Abstract]
22. Reyes C, Leyland KM, Peat G, et al. Association between overweight and obesity and risk of clinically diagnosed knee, hip, and hand osteoarthritis: a population-based cohort study. Arthritis Rheumatol. 2016 Aug;68(8):1869-75.[Abstract][Full Text]
23. Silverwood V, Blagojevic-Bucknall M, Jinks C, et al. Current evidence on risk factors for knee osteoarthritis in older adults: a systematic review and meta-analysis. Osteoarthritis Cartilage. 2015 Apr;23(4):507-15.[Abstract][Full Text]
24. Spector TD, Cicuttini F, Baker J, et al. Genetic influences on osteoarthritis in women: a twin study. BMJ. 1996;312:940-3.[Abstract]
25. Valdes AM, Spector TD. Genetic epidemiology of hip and knee osteoarthritis. Nat Rev Rheumatol. 2011 Jan;7(1):23-32.[Abstract]
26. Tanamas S, Hanna FS, Cicuttini FM, et al. Does knee malalignment increase the risk of development and progression of knee osteoarthritis? A systematic review. Arthritis Rheum. 2009 Apr 15;61(4):459-67.[Abstract][Full Text]
27. Brouwer GM, van Tol AW, Bergink AP, et al. Association between valgus and varus alignment and the development and progression of radiographic osteoarthritis of the knee. Arthritis Rheum. 2007 Apr;56(4):1204-11.[Abstract][Full Text]
28. van Buuren MMA, Arden NK, Bierma-Zeinstra SMA, et al. Statistical shape modeling of the hip and the association with hip osteoarthritis: a systematic review. Osteoarthr Cartil. 2021 May;29(5):607-18.[Abstract][Full Text]
29. Cinque ME, Dornan GJ, Chahla J, et al. High rates of osteoarthritis develop after anterior cruciate ligament surgery: an analysis of 4108 patients. Am J Sports Med. 2018 Jul;46(8):2011-19.[Abstract]
30. Chen T, Wang S, Li Y, et al. Radiographic osteoarthritis prevalence over ten years after anterior cruciate ligament reconstruction. Int J Sports Med. 2019 Oct;40(11):683-95.[Abstract][Full Text]
31. Cerejo R, Dunlop DD, Cahue S, et al. The influence of alignment on risk of knee osteoarthritis progression according to baseline stage of disease. Arthritis Rheum. 2002 Oct;46(10):2632-6.[Abstract][Full Text]
32. Chang A, Hayes K, Dunlop D, et al. Thrust during ambulation and progression of knee osteoarthritis. Arthritis Rheum. 2004;50:3897-903.[Abstract]
33. Felson DT. Clinical practice. Osteoarthritis of the knee. N Engl J Med. 2006;354:841-8.[Abstract]
34. Heinemeier KM, Schjerling P, Heinemeier J, et al. Radiocarbon dating reveals minimal collagen turnover in both healthy and osteoarthritic human cartilage. Sci Transl Med. 2016 Jul 6;8(346):346ra90.[Abstract]
35. Sohn DH, Sokolove J, Sharpe O, et al. Plasma proteins present in osteoarthritic synovial fluid can stimulate cytokine production via Toll-like receptor 4. Arthritis Res Ther. 2012 Jan 8;14(1):R7.[Abstract][Full Text]
36. Li T, Chubinskaya S, Esposito A, et al. TGF-beta type 2 receptor-mediated modulation of the IL-36 family can be therapeutically targeted in osteoarthritis. Sci Transl Med. 2019 May 8;11(491):eaan2585.[Abstract][Full Text]
37. Budhiparama NC, Lumban-Gaol I, Sudoyo H, et al. Interleukin-1 genetic polymorphisms in knee osteoarthritis: What do we know? A meta-analysis and systematic review. J Orthop Surg (Hong Kong). 2022 Jan-Apr;30(1):23094990221076652.[Abstract][Full Text]
38. Lee YH, Song GG. Association between IL-17 gene polymorphisms and circulating IL-17 levels in osteoarthritis: a meta-analysis. Z Rheumatol. 2020 Jun;79(5):482-90.[Abstract]
39. Gao S, Mao C, Cheng J, et al. Association of IL-17A-197G/A and IL-17F-7488T/C polymorphisms and osteoarthritis susceptibility: a meta-analysis. Int J Rheum Dis. 2020 Jan;23(1):37-46.[Abstract]
40. Tu M, Yao Y, Qiao FH, et al. The pathogenic role of connective tissue growth factor in osteoarthritis. Biosci Rep. 2019 Jul 31;39(7):BSR20191374.[Abstract][Full Text]
41. Troeberg L, Nagase H. Proteases involved in cartilage matrix degradation in osteoarthritis. Biochim Biophys Acta. 2012 Jan;1824(1):133-45.[Abstract][Full Text]
42. Loeser RF, Collins JA, Diekman BO. Ageing and the pathogenesis of osteoarthritis. Nat Rev Rheumatol. 2016 Jul;12(7):412-20.[Abstract][Full Text]
43. Coryell PR, Diekman BO, Loeser RF. Mechanisms and therapeutic implications of cellular senescence in osteoarthritis. Nat Rev Rheumatol. 2021 Jan;17(1):47-57.[Abstract]
44. Van Pevenage PM, Birchmier JT, June RK. Utilizing metabolomics to identify potential biomarkers and perturbed metabolic pathways in osteoarthritis: a systematic review. Semin Arthritis Rheum. 2023 Apr;59:152163.[Abstract][Full Text]
45. Zheng L, Zhang Z, Sheng P, et al. The role of metabolism in chondrocyte dysfunction and the progression of osteoarthritis. Ageing Res Rev. 2021 Mar;66:101249.[Abstract][Full Text]
46. Lee YH, Song GG. Circulating leptin level in osteoarthritis and associations between leptin receptor polymorphisms and disease susceptibility: a meta-analysis. Int J Rheum Dis. 2023 Jul;26(7):1305-13.[Abstract]
47. Chen B, Ning K, Sun ML, et al. Regulation and therapy, the role of JAK2/STAT3 signaling pathway in OA: a systematic review. Cell Commun Signal. 2023 Apr 3;21(1):67.[Abstract][Full Text]
48. Sharma L, Song J, Felson DT, et al. The role of knee alignment in disease progression and functional decline in knee osteoarthritis. JAMA. 2001;286:188-195.[Abstract]
49. Hart DJ, Doyle DV, Spector TD. Incidence and risk factors for radiographic knee osteoarthritis in middle-aged women: the Chingford Study. Arthritis Rheum. 1999;42:17-24.[Abstract]
50. Kallman DA, Wigley FM, Scott WW Jr, et al. The longitudinal course of hand osteoarthritis in a male population. Arthritis Rheum. 1990;33:1323-1331.[Abstract]
51. Felson DT, Zhang Y, Hannan MT, et al. Risk factors for incident radiographic knee osteoarthritis in the elderly: the Framingham Study. Arthritis Rheum. 1997 Apr;40(4):728-33.[Abstract][Full Text]
52. Felson DT, Anderson JJ, Naimark A, et al. Obesity and knee osteoarthritis. The Framingham Study. Ann Intern Med. 1988;109:18-24.[Abstract]
53. Francomano CA, Liberfarb RM, Hirose T, et al. The Stickler syndrome: evidence for close linkage to the structural gene for type II collagen. Genomics. 1987;1:293-6.[Abstract]
54. Kannu P, Bateman JF, Randle S, et al. Premature arthritis is a distinct type II collagen phenotype. Arthritis Rheum. 2010 May;62(5):1421-30.[Abstract][Full Text]
55. Kannu P, Bateman J, Savarirayan R. Clinical phenotypes associated with type II collagen mutations. J Paediatr Child Health. 2012 Feb;48(2):E38-43.[Abstract]
56. Zhang W, Doherty M, Leeb BF, et al. EULAR evidence-based recommendations for the diagnosis of hand osteoarthritis: report of a task force of ESCISIT. Ann Rheum Dis. 2009 Jan;68(1):8-17.[Abstract][Full Text]
57. Casartelli NC, Maffiuletti NA, Valenzuela PL, et al. Is hip morphology a risk factor for developing hip osteoarthritis? A systematic review with meta-analysis. Osteoarthr Cartil. 2021 Sep;29(9):1252-64.[Abstract][Full Text]
58. Cooper C. Occupational activity and the risk of osteoarthritis. J Rheumatol Suppl. 1995;22(Suppl 43):10-12.[Abstract]
59. Maetzel A, Makela M, Hawker G, et al. Osteoarthritis of the hip and knee and mechanical occupational exposure - a systematic overview of the evidence. J Rheumatol. 1997;24:1599-1607.[Abstract]
60. Sapolsky HM. Prospective payment in perspective. J Health Polit Policy Law. 1986;11(4):633-45.[Abstract]
61. Croft P, Cooper C, Wickham C, et al. Osteoarthritis of the hip and occupational activity. Scand J Work Env Health. 1992;18:59-63.[Abstract]
62. Driban JB, Hootman JM, Sitler MR, et al. Is participation in certain sports associated with knee osteoarthritis? A systematic review. J Athl Train. 2017 Jun 2;52(6):497-506.[Abstract][Full Text]
63. Whittaker JL, Losciale JM, Juhl CB, et al. Risk factors for knee osteoarthritis after traumatic knee injury: a systematic review and meta-analysis of randomised controlled trials and cohort studies for the OPTIKNEE Consensus. Br J Sports Med. 2022 Dec;56(24):1406-21.[Abstract][Full Text]
64. Webster KE, Hewett TE. Anterior cruciate ligament injury and knee osteoarthritis: an umbrella systematic review and meta-analysis. Clin J Sport Med. 2022 Mar 1;32(2):145-52.[Abstract]
65. Hannan MT, Anderson JJ, Zhang Y, et al. Bone mineral density and knee osteoarthritis in elderly men and women. The Framingham Study. Arthritis Rheum. 1993;36:1671-1680.[Abstract]
66. Bergink AP, Rivadeneira F, Bierma-Zeinstra SM, et al. Are bone mineral density and fractures related to the incidence and progression of radiographic osteoarthritis of the knee, hip, and hand in elderly men and women? The Rotterdam study. Arthritis Rheumatol. 2019 Mar;71(3):361-9.[Abstract]
67. Hartley A, Hardcastle SA, Frysz M, et al. Increased development of radiographic hip osteoarthritis in individuals with high bone mass: a prospective cohort study. Arthritis Res Ther. 2021 Jan 6;23(1):4.[Abstract][Full Text]
68. Whittaker JL, Culvenor AG, Juhl CB, et al. OPTIKNEE 2022: consensus recommendations to optimise knee health after traumatic knee injury to prevent osteoarthritis. Br J Sports Med. 2022 Dec;56(24):1393-405.[Abstract][Full Text]
69. Brandt KD, Mazzuca SA, Katz BP, et al. Effects of doxycycline on progression of osteoarthritis: results of a randomized, placebo-controlled, double-blind trial. Arthritis Rheum. 2005;52:2015-2025.[Abstract]
70. da Costa BR, Nüesch E, Reichenbach S, et al. Doxycycline for osteoarthritis of the knee or hip. Cochrane Database Syst Rev. 2012 Nov 14;(11):CD007323.[Abstract]
71. Lee YH, Woo JH, Choi SJ, et al. Effect of glucosamine or chondroitin sulfate on the osteoarthritis progression: a meta-analysis. Rheumatol Int. 2010 Jan;30(3):357-63.[Abstract]
72. Kouki I, Tuffet S, Crema MD, et al. Metacarpophalangeal joint impairment in hand osteoarthritis and its association with mechanical factors: results from the digital cohort osteoarthritis design hand osteoarthritis cohort. Arthritis Care Res (Hoboken). 2022 Oct;74(10):1696-703.[Abstract]
73. National Institute for Health and Care Excellence. Osteoarthritis in over 16s: diagnosis and management. Oct 2022 [internet publication].[Full Text]
74. van Tunen JAC, Dell'Isola A, Juhl C, et al. Association of malalignment, muscular dysfunction, proprioception, laxity and abnormal joint loading with tibiofemoral knee osteoarthritis - a systematic review and meta-analysis. BMC Musculoskelet Disord. 2018 Jul 28;19(1):273.[Abstract][Full Text]
75. Altman R, Alarcon G, Appelrouth D. The American College of Rheumatology criteria for the classification and reporting of osteoarthritis of the hand. Arthritis Rheum. 1990;33:1601-1610.[Abstract]
76. Peat G, Duncan RC, Wood LR, et al. Clinical features of symptomatic patellofemoral joint osteoarthritis. Arthritis Res Ther. 2012 Mar 14;14(2):R63.[Abstract][Full Text]
77. Sakellariou G, Conaghan PG, Zhang W, et al. EULAR recommendations for the use of imaging in the clinical management of peripheral joint osteoarthritis. Ann Rheum Dis. 2017 Sep;76(9):1484-94.[Abstract][Full Text]
78. Altman R, Alarcon G, Appelrouth D. The American College of Rheumatology criteria for the classification and reporting of osteoarthritis of the hip. Arthritis Rheum. 1991;34:505-514.[Abstract]
79. Fox MG, Chang EY, Amini B, et al; Expert Panel on Musculoskeletal Imaging. ACR appropriateness criteria®: chronic knee pain. J Am Coll Radiol. 2018 Nov;15(11s):S302-12.[Abstract][Full Text]
80. Hayashi D, Roemer FW, Guermazi A. Imaging for osteoarthritis. Ann Phys Rehabil Med. 2016 Jun;59(3):161-9.[Abstract][Full Text]
81. Wesseling J, Bierma-Zeinstra SM, Kloppenburg M, et al. Worsening of pain and function over 5 years in individuals with 'early' OA is related to structural damage: data from the Osteoarthritis Initiative and CHECK (Cohort Hip & Cohort Knee) study. Ann Rheum Dis. 2015;74:347-353.[Abstract]
82. Yusuf E, Kortekaas MC, Watt I, et al. Do knee abnormalities visualised on MRI explain knee pain in knee osteoarthritis? A systematic review. Ann Rheum Dis. 2011 Jan;70(1):60-7.[Abstract]
83. Foong YC, Khan HI, Blizzard L, et al. The clinical significance, natural history and predictors of bone marrow lesion change over eight years. Arthritis Res Ther. 2014 Jul 14;16(4):R149.[Abstract][Full Text]
84. Felson DT, McLaughlin S, Goggins J, et al. Bone marrow edema and its relation to progression to knee osteoarthritis. Ann Intern Med. 2003;139:330-336.[Abstract]
85. Imhof H, Breitenseher M, Trattnig S, et al. Imaging of avascular necrosis of bone. Eur Radiol. 1997;7:180-186.[Abstract]
86. American College of Radiology; Subhas N, Wu F, et al. ACR Appropriateness Criteria® chronic extremity joint pain-suspected inflammatory arthritis, crystalline arthritis, or erosive osteoarthritis: 2022 Update. J Am Coll Radiol. 2023 May;20(5s):S20-S32.[Abstract][Full Text]
87. American College of Radiology. ACR appropriateness criteria: chronic hip pain. 2022 [internet publication].[Full Text]
88. Zhang W, Robertson J, Jones AC, et al. The placebo effect and its determinants in osteoarthritis: meta-analysis of randomised controlled trials. Ann Rheum Dis. 2008;67:1716-23. [Abstract]
89. Previtali D, Merli G, Di Laura Frattura G, et al. The long-lasting effects of "placebo injections" in knee osteoarthritis: a meta-analysis. Cartilage. 2021 Dec;13(suppl 1):185S-96S.[Abstract][Full Text]
90. Bannuru RR, McAlindon TE, Sullivan MC, et al. Effectiveness and implications of alternative placebo treatments: a systematic review and network meta-analysis of osteoarthritis trials. Ann Intern Med. 2015;163:365-372.[Abstract]
91. Bricca A, Juhl CB, Steultjens M, et al. Impact of exercise on articular cartilage in people at risk of, or with established, knee osteoarthritis: a systematic review of randomised controlled trials. Br J Sports Med. 2019 Aug;53(15):940-7.[Abstract][Full Text]
92. Gohir SA, Eek F, Kelly A, et al. Effectiveness of internet-based exercises aimed at treating knee osteoarthritis: the iBEAT-OA randomized clinical trial. JAMA Netw Open. 2021 Feb 1;4(2):e210012.[Abstract][Full Text]
93. Dong R, Wu Y, Xu S, et al. Is aquatic exercise more effective than land-based exercise for knee osteoarthritis? Medicine (Baltimore). 2018 Dec;97(52):e13823.[Abstract][Full Text]
94. Goff AJ, De Oliveira Silva D, Merolli M, et al. Patient education improves pain and function in people with knee osteoarthritis with better effects when combined with exercise therapy: a systematic review. J Physiother. 2021 Jul;67(3):177-89.[Abstract][Full Text]
95. Sasaki R, Honda Y, Oga S, et al. Effect of exercise and/or educational interventions on physical activity and pain in patients with hip/knee osteoarthritis: a systematic review with meta-analysis. PLoS One. 2022;17(11):e0275591.[Abstract][Full Text]
96. Hu L, Wang Y, Liu X, et al. Tai Chi exercise can ameliorate physical and mental health of patients with knee osteoarthritis: systematic review and meta-analysis. Clin Rehabil. 2021 Jan;35(1):64-79.[Abstract][Full Text]
97. Pitsillides A, Stasinopoulos D, Giannakou K. The effects of cognitive behavioural therapy delivered by physical therapists in knee osteoarthritis pain: a systematic review and meta-analysis of randomized controlled trials. J Bodyw Mov Ther. 2021 Jan;25:157-64.[Abstract]
98. Brosseau L, Wells GA, Pugh AG, et al. Ottawa Panel evidence-based clinical practice guidelines for therapeutic exercise in the management of hip osteoarthritis. Clin Rehabil. 2016 Oct;30(10):935-46.[Abstract]
99. Jansen MJ, Viechtbauer W, Lenssen AF, et al. Strength training alone, exercise therapy alone, and exercise therapy with passive manual mobilisation each reduce pain and disability in people with knee osteoarthritis: a systematic review. J Physiother. 2011;57:11-20.[Abstract]
100. Dziedzic K, Nicholls E, Hill S, et al. Self-management approaches for osteoarthritis in the hand: a 2x2 factorial randomised trial. Ann Rheum Dis. 2015;74:108-118.[Abstract][Full Text]
101. Anwer S, Alghadir A, Zafar H, et al. Effects of orthopaedic manual therapy in knee osteoarthritis: a systematic review and meta-analysis. Physiotherapy. 2018 Sep;104(3):264-76.[Abstract]
102. Fransen M, McConnell S, Harmer AR, et al. Exercise for osteoarthritis of the knee. Cochrane Database Syst Rev. 2015;(1):CD004376.[Abstract][Full Text]
103. Fransen M, McConnell S, Hernandez-Molina G, et al. Exercise for osteoarthritis of the hip. Cochrane Database Syst Rev. 2014;(4):CD007912.[Abstract][Full Text]
104. Bennell KL, Egerton T, Martin J, et al. Effect of physical therapy on pain and function in patients with hip osteoarthritis: a randomized clinical trial. JAMA. 2014;311:1987-1997.[Abstract][Full Text]
105. Fransen M, McConnell S, Hernandez-Molina G, et al. Does land-based exercise reduce pain and disability associated with hip osteoarthritis? A meta-analysis of randomized controlled trials. Osteoarthritis Cartilage. 2010;18:613-620.[Abstract]
106. Teirlinck CH, Verhagen AP, Reijneveld EAE, et al. Responders to exercise therapy in patients with osteoarthritis of the hip: a systematic review and meta-analysis. Int J Environ Res Public Health. 2020 Oct 10;17(20):7380.[Abstract][Full Text]
107. Thomas DT, R S, Prabhakar AJ, et al. Hip abductor strengthening in patients diagnosed with knee osteoarthritis - a systematic review and meta-analysis. BMC Musculoskelet Disord. 2022 Jun 29;23(1):622.[Abstract][Full Text]
108. Messier SP, Mihalko SL, Legault C, et al. Effects of intensive diet and exercise on knee joint loads, inflammation, and clinical outcomes among overweight and obese adults with knee osteoarthritis: the IDEA randomized clinical trial. JAMA. 2013;310:1263-1273.[Abstract][Full Text]
109. Christensen R, Henriksen M, Leeds AR, et al. Effect of weight maintenance on symptoms of knee osteoarthritis in obese patients: a twelve-month randomized controlled trial. Arthritis Care Res (Hoboken). 2015;67:640-650.[Abstract][Full Text]
110. Hislop AC, Collins NJ, Tucker K, et al. Does adding hip exercises to quadriceps exercises result in superior outcomes in pain, function and quality of life for people with knee osteoarthritis? A systematic review and meta-analysis. Br J Sports Med. 2020 Mar;54(5):263-71.[Abstract][Full Text]
111. Raghava Neelapala YV, Bhagat M, Shah P. Hip muscle strengthening for knee osteoarthritis: a systematic review of literature. J Geriatr Phys Ther. 2020 Apr/Jun;43(2):89-98.[Abstract][Full Text]
112. Jurado-Castro JM, Muñoz-López M, Ledesma AS, et al. Effectiveness of exercise in patients with overweight or obesity suffering from knee osteoarthritis: a systematic review and meta-analysis. Int J Environ Res Public Health. 2022 Aug 24;19(17):10510.[Abstract][Full Text]
113. Hall M, Castelein B, Wittoek R, et al. Diet-induced weight loss alone or combined with exercise in overweight or obese people with knee osteoarthritis: A systematic review and meta-analysis. Semin Arthritis Rheum. 2019 Apr;48(5):765-77.[Abstract]
114. Chu SF, Liou TH, Chen HC, et al. Relative efficacy of weight management, exercise, and combined treatment for muscle mass and physical sarcopenia indices in adults with overweight or obesity and osteoarthritis: a network meta-analysis of randomized controlled trials. Nutrients. 2021 Jun 10;13(6):1992.[Abstract][Full Text]
115. Huang XM, Yuan FZ, Chen YR, et al. Physical therapy and orthopaedic equipment-induced reduction in the biomechanical risk factors related to knee osteoarthritis: a systematic review and Bayesian network meta-analysis of randomised controlled trials. BMJ Open. 2022 Feb 9;12(2):e051608.[Abstract][Full Text]
116. 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. 2013;310:722-730.[Abstract][Full Text]
117. Yu L, Wang Y, Yang J, et al. Effects of orthopedic insoles on patients with knee osteoarthritis: a meta-analysis and systematic review. J Rehabil Med. 2021 May 18;53(5):jrm00191.[Abstract][Full Text]
118. Jindasakchai P, Angthong C, Panyarachun P, et al. Therapeutic significance of insoles in patients with knee osteoarthritis. Eur Rev Med Pharmacol Sci. 2023 Jun;27(11):5023-30.[Abstract][Full Text]
119. Alfatafta H, Onchonga D, Alfatafta M, et al. Effect of using knee valgus brace on pain and activity level over different time intervals among patients with medial knee OA: systematic review. BMC Musculoskelet Disord. 2021 Aug 12;22(1):687.[Abstract][Full Text]
120. Duivenvoorden T, Brouwer RW, van Raaij TM, et al. Braces and orthoses for treating osteoarthritis of the knee. Cochrane Database Syst Rev. 2015;(3):CD004020.[Abstract][Full Text]
121. Moyer RF, Birmingham TB, Bryant DM, et al. Valgus bracing for knee osteoarthritis: a meta-analysis of randomized trials. Arthritis Care Res (Hoboken). 2015;67:493-501.[Abstract]
122. Gohal C, Shanmugaraj A, Tate P, et al. Effectiveness of valgus offloading knee braces in the treatment of medial compartment knee osteoarthritis: a systematic review. Sports Health. 2018 Nov/Dec;10(6):500-14.[Abstract]
123. Fan Y, Li Z, Zhang H, et al. Valgus knee bracing may have no long-term effect on pain improvement and functional activity in patients with knee osteoarthritis: a meta-analysis of randomized trials. J Orthop Surg Res. 2020 Sep 1;15(1):373.[Abstract][Full Text]
124. Khosravi M, Babaee T, Daryabor A, et al. Effect of knee braces and insoles on clinical outcomes of individuals with medial knee osteoarthritis: a systematic review and meta-analysis. Assist Technol. 2022 Sep 3;34(5):501-17.[Abstract]
125. Hinman RS, Wrigley TV, Metcalf BR, et al. Unloading shoes for self-management of knee osteoarthritis: a randomized trial. Ann Intern Med. 2016;165:381-89.[Abstract]
126. Callaghan MJ, Parkes MJ, Hutchinson CE, et al. A randomised trial of a brace for patellofemoral osteoarthritis targeting knee pain and bone marrow lesions. Ann Rheum Dis. 2015;74:1164-70.[Abstract][Full Text]
127. Callaghan MJ, Palmer E, O'Neill T. Management of patellofemoral joint osteoarthritis using biomechanical device therapy: a systematic review with meta-analysis. Syst Rev. 2021 Jun 9;10(1):173.[Abstract][Full Text]
128. Buhler M, Chapple CM, Stebbings S, et al. Effectiveness of splinting for pain and function in people with thumb carpometacarpal osteoarthritis: a systematic review with meta-analysis. Osteoarthritis Cartilage. 2019 Apr;27(4):547-59.[Abstract][Full Text]
129. Honvo G, Reginster JY, Rabenda V, et al. Safety of symptomatic slow-acting drugs for osteoarthritis: outcomes of a systematic review and meta-analysis. Drugs Aging. 2019 Apr;36(suppl 1):65-99.[Abstract][Full Text]
130. Gregori D, Giacovelli G, Minto C, et al. Association of pharmacological treatments with long-term pain control in patients with knee osteoarthritis: a systematic review and meta-analysis. JAMA. 2018 Dec 25;320(24):2564-79.[Abstract][Full Text]
131. Simental-Mendía M, Sánchez-García A, Vilchez-Cavazos F, et al. Effect of glucosamine and chondroitin sulfate in symptomatic knee osteoarthritis: a systematic review and meta-analysis of randomized placebo-controlled trials. Rheumatol Int. 2018 Aug;38(8):1413-28.[Abstract]
132. Singh JA, Noorbaloochi S, MacDonald R, et al. Chondroitin for osteoarthritis. Cochrane Database Syst Rev. 2015;(1):CD005614.[Abstract][Full Text]
133. Ogata T, Ideno Y, Akai M, et al. Effects of glucosamine in patients with osteoarthritis of the knee: a systematic review and meta-analysis. Clin Rheumatol. 2018 Sep;37(9):2479-87.[Abstract][Full Text]
134. Knapik JJ, Pope R, Hoedebecke SS, et al. Effects of oral chondroitin sulfate on osteoarthritis-related pain and joint structural changes: systematic review and meta-analysis. J Spec Oper Med. Spring 2019;19(1):113-24.[Abstract]
135. Meng Z, Liu J, Zhou N. Efficacy and safety of the combination of glucosamine and chondroitin for knee osteoarthritis: a systematic review and meta-analysis. Arch Orthop Trauma Surg. 2023 Jan;143(1):409-21.[Abstract]
136. Bruyère O, Honvo G, Veronese N, et al. An updated algorithm recommendation for the management of knee osteoarthritis from the European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO). Semin Arthritis Rheum. 2019 Dec;49(3):337-50.[Abstract][Full Text]
137. Suarez-Almazor ME, Looney C, Liu Y, et al. A randomized controlled trial of acupuncture for osteoarthritis of the knee: effects of patient-provider communication. Arthritis Care Res (Hoboken). 2010;62:1229-1236.[Abstract]
138. Kwon YD, Pittler MH, Ernst E. Acupuncture for peripheral joint osteoarthritis: a systematic review and meta-analysis. Rheumatology (Oxford). 2006;45:1331-1337.[Abstract][Full Text]
139. Cao L, Zhang XL, Gao YS, et al. Needle acupuncture for osteoarthritis of the knee. A systematic review and updated meta-analysis. Saudi Med J. 2012;33:526-532.[Abstract]
140. Araya-Quintanilla F, Cuyúl-Vásquez I, Gutiérrez-Espinoza H. Does acupuncture provide pain relief in patients with osteoarthritis knee? An overview of systematic reviews. J Bodyw Mov Ther. 2022 Jan;29:117-26.[Abstract]
141. Manheimer E, Cheng K, Wieland LS, et al. Acupuncture for hip osteoarthritis. Cochrane Database Syst Rev. 2018 May 5;(5):CD013010.[Abstract][Full Text]
142. Tian H, Huang L, Sun M, et al. Acupuncture for knee osteoarthritis: a systematic review of randomized clinical trials with meta-analyses and trial sequential analyses. Biomed Res Int. 2022;2022:6561633.[Abstract][Full Text]
143. Kwak SG, Kwon JB, Seo YW, et al. The effectiveness of acupuncture as an adjunctive therapy to oral pharmacological medication in patient with knee osteoarthritis: a systematic review and meta-analysis. Medicine (Baltimore). 2023 Mar 17;102(11):e33262.[Abstract][Full Text]
144. Rutjes AW, Nüesch E, Sterchi R, et al. Transcutaneous electrostimulation for osteoarthritis of the knee. Cochrane Database Syst Rev. 2009 Oct 7;(4):CD002823.[Abstract][Full Text]
145. Wu Y, Zhu F, Chen W, et al. Effects of transcutaneous electrical nerve stimulation (TENS) in people with knee osteoarthritis: a systematic review and meta-analysis. Clin Rehabil. 2022 Apr;36(4):472-85.[Abstract]
146. Stewart M, Cibere J, Sayre EC, et al. Efficacy of commonly prescribed analgesics in the management of osteoarthritis: a systematic review and meta-analysis. Rheumatol Int. 2018 Nov;38(11):1985-97.[Abstract]
147. da Costa BR, Pereira TV, Saadat P, et al. Effectiveness and safety of non-steroidal anti-inflammatory drugs and opioid treatment for knee and hip osteoarthritis: network meta-analysis. BMJ. 2021 Oct 12;375:n2321.[Abstract][Full Text]
148. Zeng C, Wei J, Persson MS, et al. Relative efficacy and safety of topical non-steroidal anti-inflammatory drugs for osteoarthritis: a systematic review and network meta-analysis of randomised controlled trials and observational studies. Br J Sports Med. 2018 May;52(10):642-50.[Abstract][Full Text]
149. Sardana V, Burzynski J, Zalzal P. Safety and efficacy of topical ketoprofen in transfersome gel in knee osteoarthritis: a systematic review. Musculoskeletal Care. 2017 Jun;15(2):114-21.[Abstract]
150. Honvo G, Leclercq V, Geerinck A, et al. Safety of topical non-steroidal anti-inflammatory drugs in osteoarthritis: outcomes of a systematic review and meta-analysis. Drugs Aging. 2019 Apr;36(suppl 1):45-64.[Abstract][Full Text]
151. Ling T, Li JJ, Xu RJ, et al. Topical Diclofenac Solution for Osteoarthritis of the Knee: An Updated Meta-Analysis of Randomized Controlled Trials. Biomed Res Int. 2020;2020:1758071.[Abstract][Full Text]
152. Cameron M, Chrubasik S. Topical herbal therapies for treating osteoarthritis. Cochrane Database Syst Rev. 2013;(5):CD010538.[Abstract][Full Text]
153. Persson MSM, Stocks J, Walsh DA, et al. The relative efficacy of topical non-steroidal anti-inflammatory drugs and capsaicin in osteoarthritis: a network meta-analysis of randomised controlled trials. Osteoarthritis Cartilage. 2018 Dec;26(12):1575-82.[Abstract][Full Text]
154. Machado GC, Maher CG, Ferreira PH, et al. Efficacy and safety of paracetamol for spinal pain and osteoarthritis: systematic review and meta-analysis of randomised placebo controlled trials. BMJ. 2015;350:h1225.[Abstract][Full Text]
155. Abdel Shaheed C, Ferreira GE, Dmitritchenko A, et al. The efficacy and safety of paracetamol for pain relief: an overview of systematic reviews. Med J Aust. 2021 Apr;214(7):324-31.[Abstract][Full Text]
156. da Costa BR, Reichenbach S, Keller N, et al. Effectiveness of non-steroidal anti-inflammatory drugs for the treatment of pain in knee and hip osteoarthritis: a network meta-analysis. Lancet. 2017 Jul 8;390(10090):e21-33.[Abstract]
157. Leopoldino AO, Machado GC, Ferreira PH, et al. Paracetamol versus placebo for knee and hip osteoarthritis. Cochrane Database Syst Rev. 2019 Feb 25;(2):CD013273.[Abstract][Full Text]
158. Bannuru RR, Schmid CH, Kent DM, et al. Comparative effectiveness of pharmacologic interventions for knee osteoarthritis: a systematic review and network meta-analysis. Ann Intern Med. 2015;162:46-54.[Abstract]
159. Machado GC, Abdel-Shaheed C, Underwood M, et al. Non-steroidal anti-inflammatory drugs (NSAIDs) for musculoskeletal pain. BMJ. 2021 Jan 29;372:n104.[Abstract]
160. Yeomans ND, Tulassay Z, Juhasz L, et al; Acid suppression trial: ranitidine versus omeprazole for NSAID-associated ulcer treatment (ASTRONAUT) study group. A comparison of omeprazole with ranitidine for ulcers associated with nonsteroidal antiinflammatory drugs. N Engl J Med. 1998;338:719-26.[Abstract][Full Text]
161. Hawkey CJ, Karrasch JA, Szczepanski L, et al. Omeprazole compared with misoprostol for ulcers associated with nonsteroidal antiinflammatory drugs. N Engl J Med. 1998;338:727-734.[Abstract][Full Text]
162. Elliott SL, Yeomans ND, Buchanan RR, et al. Efficacy of 12 months' misoprostol as prophylaxis against NSAID-induced gastric ulcers. A placebo-controlled trial. Scand J Rheumatol. 1994;23:171-176.[Abstract]
163. Graham DY, Agrawal NM, Roth SH. Prevention of NSAID-induced gastric ulcer with misoprostol: multicentre, double-blind, placebo-controlled trial. Lancet. 1988;2:1277-1280.[Abstract]
164. Graham DJ, Campen D, Hui R, et al. Risk of acute myocardial infarction and sudden cardiac death in patients treated with cyclo-oxygenase 2 selective and non-selective non-steroidal anti-inflammatory drugs: nested case-control study. Lancet. 2005;365:475-481.[Abstract]
165. Maxwell SR, Payne RA, Murray GD, et al. Selectivity of NSAIDs for COX-2 and cardiovascular outcome. Br J Clin Pharmacol. 2006;62:243-245.[Abstract]
166. Wang X, Tian HJ, Yang HK, et al. Meta-analysis: cyclooxygenase-2 inhibitors are no better than nonselective nonsteroidal anti-inflammatory drugs with proton pump inhibitors in regard to gastrointestinal adverse events in osteoarthritis and rheumatoid arthritis. Eur J Gastroenterol Hepatol. 2011;23:876-880.[Abstract]
167. Curtis E, Fuggle N, Shaw S, et al. Safety of cyclooxygenase-2 inhibitors in osteoarthritis: outcomes of a systematic review and meta-analysis. Drugs Aging. 2019 Apr;36(suppl 1):25-44.[Abstract][Full Text]
168. Cryer BL, Sostek MB, Fort JG, et al. A fixed-dose combination of naproxen and esomeprazole magnesium has comparable upper gastrointestinal tolerability to celecoxib in patients with osteoarthritis of the knee: results from two randomized, parallel-group, placebo-controlled trials. Ann Med. 2011;43:594-605.[Abstract]
169. Atiquzzaman M, Karim ME, Kopec J, et al. Role of nonsteroidal antiinflammatory drugs in the association between osteoarthritis and cardiovascular diseases: a longitudinal study. Arthritis Rheumatol. 2019 Nov;71(11):1835-43.[Abstract]
170. Osani MC, Vaysbrot EE, Zhou M, et al. Duration of symptom relief and early trajectory of adverse events for oral nonsteroidal antiinflammatory drugs in knee osteoarthritis: a systematic review and meta-analysis. Arthritis Care Res (Hoboken). 2020 May;72(5):641-51.[Abstract][Full Text]
171. Solomon DH, Glynn RJ, Rothman KJ, et al. Subgroup analyses to determine cardiovascular risk associated with nonsteroidal antiinflammatory drugs and coxibs in specific patient groups. Arthritis Rheum. 2008;59:1097-1104.[Abstract][Full Text]
172. Antman EM, DeMets D, Loscalzo J. Cyclooxygenase inhibition and cardiovascular risk. Circulation. 2005;112:759-770.[Abstract][Full Text]
173. Nissen SE. Cardiovascular safety of celecoxib, naproxen, or ibuprofen for arthritis. N Engl J Med. 2017 Apr 6;376(14):1390.[Abstract]
174. Osani MC, Lohmander LS, Bannuru RR. Is There any role for opioids in the management of knee and hip osteoarthritis? A systematic review and meta-analysis. Arthritis Care Res (Hoboken). 2021 Oct;73(10):1413-24.[Abstract][Full Text]
175. 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;(9):CD003115.[Abstract][Full Text]
176. Welsch P, Petzke F, Klose P, et al. Opioids for chronic osteoarthritis pain: an updated systematic review and meta-analysis of efficacy, tolerability and safety in randomized placebo-controlled studies of at least 4 weeks double-blind duration. Eur J Pain. 2020 Apr;24(4):685-703.[Abstract][Full Text]
177. Toupin April K, Bisaillon J, Welch V, et al. Tramadol for osteoarthritis. Cochrane Database Syst Rev. 2019 May 27;(5):CD005522.[Abstract][Full Text]
178. Zhang X, Li X, Xiong Y, et al. Efficacy and safety of tramadol for knee or hip osteoarthritis: a systematic review and network meta-analysis of randomized controlled trials. Arthritis Care Res (Hoboken). 2023 Jan;75(1):158-65.[Abstract]
179. Citrome L, Weiss-Citrome A. A systematic review of duloxetine for osteoarthritic pain: what is the number needed to treat, number needed to harm, and likelihood to be helped or harmed? Postgrad Med. 2012;124:83-93.[Abstract]
180. Myers J, Wielage RC, Han B, et al. The efficacy of duloxetine, non-steroidal anti-inflammatory drugs, and opioids in osteoarthritis: a systematic literature review and meta-analysis. BMC Musculoskelet Disord. 2014 Mar 11;15:76.[Abstract][Full Text]
181. Osani MC, Bannuru RR. Efficacy and safety of duloxetine in osteoarthritis: a systematic review and meta-analysis. Korean J Intern Med. 2019 Sep;34(5):966-73.[Abstract][Full Text]
182. Chen L, Gong M, Liu G, et al. Efficacy and tolerability of duloxetine in patients with knee osteoarthritis: a meta-analysis of randomised controlled trials. Intern Med J. 2019 Dec;49(12):1514-23.[Abstract]
183. Weng C, Xu J, Wang Q, et al. Efficacy and safety of duloxetine in osteoarthritis or chronic low back pain: a systematic review and meta-analysis. Osteoarthritis Cartilage. 2020 Jun;28(6):721-34.[Abstract][Full Text]
184. Chen B, Duan J, Wen S, et al. An updated systematic review and meta-analysis of duloxetine for knee osteoarthritis Pain. Clin J Pain. 2021 Nov 1;37(11):852-62.[Abstract][Full Text]
185. Saltzman BM, Leroux T, Meyer MA, et al. The therapeutic effect of intra-articular normal saline injections for knee osteoarthritis: a meta-analysis of evidence level 1 studies. Am J Sports Med. 2017 Sep;45(11):2647-53.[Abstract]
186. Gazendam A, Ekhtiari S, Bozzo A, et al. Intra-articular saline injection is as effective as corticosteroids, platelet-rich plasma and hyaluronic acid for hip osteoarthritis pain: a systematic review and network meta-analysis of randomised controlled trials. Br J Sports Med. 2021 Mar;55(5):256-61.[Abstract][Full Text]
187. Jüni P, Hari R, Rutjes AW, et al. Intra-articular corticosteroid for knee osteoarthritis. Cochrane Database Syst Rev. 2015 Oct 22;(10):CD005328.[Abstract][Full Text]
188. McCabe PS, Maricar N, Parkes MJ, et al. The efficacy of intra-articular steroids in hip osteoarthritis: a systematic review. Osteoarthritis Cartilage. 2016 Sep;24(9):1509-17.[Abstract][Full Text]
189. Najm A, Alunno A, Gwinnutt JM, et al. Efficacy of intra-articular corticosteroid injections in knee osteoarthritis: a systematic review and meta-analysis of randomized controlled trials. Joint Bone Spine. 2021 Jul;88(4):105198.[Abstract]
190. Wang X, Wang P, Faramand A, et al. Efficacy and safety of corticosteroid in the treatment of hand osteoarthritis: a systematic review and meta-analysis of randomized controlled trials. Clin Rheumatol. 2022 Jun;41(6):1825-32.[Abstract]
191. Xie Y, Zhao K, Ye G, et al. Effectiveness of intra-articular injections of sodium hyaluronate, corticosteroids, platelet-rich plasma on temporomandibular joint osteoarthritis: a systematic review and network meta-analysis of randomized controlled trials. J Evid Based Dent Pract. 2022 Sep;22(3):101720.[Abstract]
192. Choueiri M, Chevalier X, Eymard F. Intraarticular corticosteroids for hip osteoarthritis: a review. Cartilage. 2021 Dec;13(suppl 1):122S-31S.[Abstract][Full Text]
193. Zhong HM, Zhao GF, Lin T, et al. Intra-articular steroid injection for patients with hip osteoarthritis: a systematic review and meta-analysis. Biomed Res Int. 2020;2020:6320154.[Abstract][Full Text]
194. Okike K, King RK, Merchant JC, et al. Rapidly destructive hip disease following intra-articular corticosteroid injection of the hip. J Bone Joint Surg Am. 2021 Nov 17;103(22):2070-79.[Abstract]
195. van Middelkoop M, Arden NK, Atchia I, et al. The OA Trial Bank: meta-analysis of individual patient data from knee and hip osteoarthritis trials show that patients with severe pain exhibit greater benefit from intra-articular glucocorticoids. Osteoarthritis Cartilage. 2016 Jul;24(7):1143-52.[Abstract][Full Text]
196. 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: a randomized clinical trial. JAMA. 2017 May 16;317(19):1967-75.[Abstract][Full Text]
197. Raynauld JP, Buckland-Wright C, Ward R, et al. Safety and efficacy of long-term intraarticular steroid injections in osteoarthritis of the knee: a randomized, double-blind, placebo-controlled trial. Arthritis Rheum. 2003 Feb;48(2):370-7.[Abstract][Full Text]
198. Donovan RL, Edwards TA, Judge A, et al. Effects of recurrent intra-articular corticosteroid injections for osteoarthritis at 3 months and beyond: a systematic review and meta-analysis in comparison to other injectables. Osteoarthritis Cartilage. 2022 Dec;30(12):1658-69.[Abstract][Full Text]
199. Bannuru RR, Natov NS, Obadan IE, et al. Therapeutic trajectory of hyaluronic acid versus corticosteroids in the treatment of knee osteoarthritis: a systematic review and meta-analysis. Arthritis Rheum. 2009;61:1704-1711.[Abstract]
200. Leite VF, Daud Amadera JE, Buehler AM. Viscosupplementation for hip osteoarthritis: a systematic review and meta-analysis of the efficacy on pain and disability, and the occurrence of adverse events. Arch Phys Med Rehabil. 2018 Mar;99(3):574-83.e1.[Abstract]
201. Bellamy N, Campbell J, Welch V, et al. Viscosupplementation for the treatment of osteoarthritis of the knee. Cochrane Database Syst Rev. 2006 Apr 19;(2):CD005321.[Abstract][Full Text]
202. Maheu E, Bannuru RR, Herrero-Beaumont G, et al. Why we should definitely include intra-articular hyaluronic acid as a therapeutic option in the management of knee osteoarthritis: results of an extensive critical literature review. Semin Arthritis Rheum. 2019 Feb;48(4):563-72.[Abstract][Full Text]
203. Richette P, Chevalier X, Ea HK, et al. Hyaluronan for knee osteoarthritis: an updated meta-analysis of trials with low risk of bias. RMD Open. 2015 May 14;1(1):e000071.[Abstract][Full Text]
204. Pereira TV, Jüni P, Saadat P, et al. Viscosupplementation for knee osteoarthritis: systematic review and meta-analysis. BMJ. 2022 Jul 6;378:e069722.[Abstract][Full Text]
205. Skou ST, Roos EM, Laursen MB, et al. A randomized, controlled trial of total knee replacement. N Engl J Med. 2015;373:1597-1606.[Abstract][Full Text]
206. Kyriakidis T, Asopa V, Baums M, et al. Unicompartmental knee arthroplasty in patients under the age of 60 years provides excellent clinical outcomes and 10-year implant survival: a systematic review : a study performed by the Early Osteoarthritis group of ESSKA-European Knee Associates section. Knee Surg Sports Traumatol Arthrosc. 2023 Mar;31(3):922-32.[Abstract]
207. Katz JN, Brophy RH, Chaisson CE, et al. Surgery versus physical therapy for a meniscal tear and osteoarthritis. N Engl J Med. 2013;368:1675-1684.[Abstract][Full Text]
208. Moseley JB, O'Malley K, Petersen NJ, et al. A controlled trial of arthroscopic surgery for osteoarthritis of the knee. N Engl J Med. 2002 Jul 11;347(2):81-8.[Abstract][Full Text]
209. O'Connor D, Johnston RV, Brignardello-Petersen R, et al. Arthroscopic surgery for degenerative knee disease (osteoarthritis including degenerative meniscal tears). Cochrane Database Syst Rev. 2022 Mar 3;3(3):CD014328.[Abstract][Full Text]
210. Singh Jagdev B, McGrath J, Cole A, et al. Total shoulder arthroplasty vs. hemiarthroplasty in patients with primary glenohumeral arthritis with intact rotator cuff: meta-analysis using the ratio of means. J Shoulder Elbow Surg. 2022 Dec;31(12):2657-70.[Abstract]
211. Gandolfi S, Carloni R, Mouton J, et al. Finger joint denervation in hand osteoarthritis: indications, surgical techniques and outcomes. A systematic review of published cases. Hand Surg Rehabil. 2020 Sep;39(4):239-50.[Abstract]
212. Zhu SL, Chin B, Sarraj M, et al. Denervation as a treatment for arthritis of the hands: a systematic review of the current literature. Hand (N Y). 2023 Mar;18(2):183-91.[Abstract][Full Text]
213. Kloppenburg M, Kroon FP, Blanco FJ, et al. 2018 update of the EULAR recommendations for the management of hand osteoarthritis. Ann Rheum Dis. 2019 Jan;78(1):16-24.[Abstract][Full Text]
214. Knightly N, Sullivan P. Surgery for trapeziometacarpal joint osteoarthritis: a meta-analysis on efficacy and safety. J Hand Surg Asian Pac Vol. 2021 Jun;26(2):245-64.[Abstract]
215. Pozzobon D, Ferreira PH, Blyth FM, et al. Can obesity and physical activity predict outcomes of elective knee or hip surgery due to osteoarthritis? A meta-analysis of cohort studies. BMJ Open. 2018 Feb 27;8(2):e017689.[Abstract][Full Text]
216. Wallis JA, Taylor NF. Pre-operative interventions (non-surgical and non-pharmacological) for patients with hip or knee osteoarthritis awaiting joint replacement surgery - a systematic review and meta-analysis. Osteoarthritis Cartilage. 2011;19:1381-1395.[Abstract]
217. Schairer WW, Nwachukwu BU, Mayman DJ, et al. Preoperative hip injections increase the rate of periprosthetic infection after total hip arthroplasty. J Arthroplasty. 2016;31(suppl):S166-S169.[Abstract]
218. Werner BC, Cancienne JM, Browne JA. The timing of total hip arthroplasty after intraarticular hip injection affects postoperative infection risk. J Arthroplasty. 2016;31:820-823.[Abstract]
219. Li J, Li YX, Luo LJ, et al. The effectiveness and safety of acupuncture for knee osteoarthritis: an overview of systematic reviews. Medicine (Baltimore). 2019 Jul;98(28):e16301.[Abstract][Full Text]
220. Ahmed I, Gertner E. Safety of arthrocentesis and joint injection in patients receiving anticoagulation at therapeutic levels. Am J Med. 2012 Mar;125(3):265-9.[Abstract][Full Text]
221. Bashir MA, Ray R, Sarda P, et al. Determination of a safe INR for joint injections in patients taking warfarin. Ann R Coll Surg Engl. 2015 Nov;97(8):589-91.[Abstract][Full Text]
222. The Primary Care Rheumatology and Musculoskeletal Medicine Society. Joint and Soft Tissue Injection Recommendations. 2021 [internet publication].[Full Text]
223. Avendaño-Coy J, Comino-Suárez N, Grande-Muñoz J, et al. Extracorporeal shockwave therapy improves pain and function in subjects with knee osteoarthritis: a systematic review and meta-analysis of randomized clinical trials. Int J Surg. 2020 Oct;82:64-75.[Abstract][Full Text]
224. Ma H, Zhang W, Shi J, et al. The efficacy and safety of extracorporeal shockwave therapy in knee osteoarthritis: a systematic review and meta-analysis. Int J Surg. 2020 Mar;75:24-34.[Abstract][Full Text]
225. Wang YC, Huang HT, Huang PJ, et al. Efficacy and safety of extracorporeal shockwave therapy for treatment of knee osteoarthritis: a systematic review and meta-analysis. Pain Med. 2020 Apr 1;21(4):822-35.[Abstract][Full Text]
226. Leone R, de Rosa A, Iudicone P, et al. Pain control and functional improvement in patients treated by autologous conditioned serum after failure of platelet rich plasma treatments in knee osteoarthritis. Transfus Med. 2021 Oct;31(5):357-64.[Abstract]
227. Simon MJK, Aartsen VE, Coghlan JA, et al. Shoulder injections with autologous conditioned serum reduce pain and disability in glenohumeral osteoarthritis: longitudinal observational study. ANZ J Surg. 2021 Apr;91(4):673-9.[Abstract][Full Text]
228. Zarringam D, Bekkers JE, Saris DB. Long-term effect of injection treatment for osteoarthritis in the knee by orthokin autologous conditioned serum. Cartilage. 2018 Apr;9(2):140-5.[Abstract][Full Text]
229. Baltzer AW, Moser C, Jansen SA, et al. Autologous conditioned serum (Orthokine) is an effective treatment for knee osteoarthritis. Osteoarthritis Cartilage. 2009;17:152-160.[Abstract]
230. Khoshbin A, Leroux T, Wasserstein D, et al. The efficacy of platelet-rich plasma in the treatment of symptomatic knee osteoarthritis: a systematic review with quantitative synthesis. Arthroscopy. 2013;29:2037-2048.[Abstract]
231. Campbell KA, Saltzman BM, Mascarenhas R, et al. Does intra-articular platelet-rich plasma injection provide clinically superior outcomes compared with other therapies in the treatment of knee osteoarthritis? A systematic review of overlapping meta-analyses. Arthroscopy. 2015;31:2213-2221.[Abstract]
232. Ye Y, Zhou X, Mao S, et al. Platelet rich plasma versus hyaluronic acid in patients with hip osteoarthritis: a meta-analysis of randomized controlled trials. Int J Surg. 2018 May;53:279-87.[Abstract]
233. Chen P, Huang L, Ma Y, et al. Intra-articular platelet-rich plasma injection for knee osteoarthritis: a summary of meta-analyses. J Orthop Surg Res. 2019 Nov 27;14(1):385.[Abstract][Full Text]
234. Dong Y, Zhang B, Yang Q, et al. The effects of platelet-rich plasma injection in knee and hip osteoarthritis: a meta-analysis of randomized controlled trials. Clin Rheumatol. 2021 Jan;40(1):263-77.[Abstract]
235. Berney M, McCarroll P, Glynn L, et al. Platelet-rich plasma injections for hip osteoarthritis: a review of the evidence. Ir J Med Sci. 2021 Aug;190(3):1021-25.[Abstract]
236. Laohajaroensombat S, Prusmetikul S, Rattanasiri S, et al. Platelet-rich plasma injection for the treatment of ankle osteoarthritis: a systematic review and meta-analysis. J Orthop Surg Res. 2023 May 19;18(1):373.[Abstract][Full Text]
237. National Institute for Health and Care Excellence. Platelet-rich plasma injections for knee osteoarthritis. Jan 2019 [internet publication].[Full Text]
238. Belk JW, Lim JJ, Keeter C, et al. Patients with knee osteoarthritis who receive platelet-rich plasma or bone marrow aspirate concentrate injections have better outcomes than patients who receive hyaluronic acid: systematic review and meta-analysis. Arthroscopy. 2023 Jul;39(7):1714-34.[Abstract]
239. Belk JW, Kraeutler MJ, Houck DA, et al. Platelet-rich plasma versus hyaluronic acid for knee osteoarthritis: a systematic review and meta-analysis of randomized controlled trials. Am J Sports Med. 2021 Jan;49(1):249-60.[Abstract][Full Text]
240. Belk JW, Houck DA, Littlefield CP, et al. Platelet-rich plasma versus hyaluronic acid for hip osteoarthritis yields similarly beneficial short-term clinical outcomes: a systematic review and meta-analysis of Level I and II randomized controlled trials. Arthroscopy. 2022 Jun;38(6):2035-46.[Abstract][Full Text]
241. Filardo G, Previtali D, Napoli F, et al. PRP injections for the treatment of knee osteoarthritis: a meta-analysis of rndomized controlled trials. Cartilage. 2021 Dec;13(suppl 1):364S-75S.[Abstract][Full Text]
242. Paget LDA, Reurink G, de Vos RJ, et al. Platelet-rich plasma injections for the treatment of ankle osteoarthritis. Am J Sports Med. 2023 Aug;51(10):2625-34.[Abstract][Full Text]
243. Chou SH, Shen PC, Lu CC, et al. Comparison of efficacy among three radiofrequency ablation techniques for treating knee osteoarthritis: a systematic review and meta-analysis. Int J Environ Res Public Health. 2021 Jul 12;18(14):7424.[Abstract][Full Text]
244. Gupta A, Huettner DP, Dukewich M. Comparative effectiveness review of cooled versus pulsed radiofrequency ablation for the treatment of knee osteoarthritis: a systematic review. Pain Physician. 2017 Mar;20(3):155-71.[Abstract][Full Text]
245. Ajrawat P, Radomski L, Bhatia A, et al. Radiofrequency procedures for the treatment of symptomatic knee osteoarthritis: a systematic review. Pain Med. 2020 Feb 1;21(2):333-48.[Abstract][Full Text]
246. Fogarty AE, Burnham T, Kuo K, et al. The effectiveness of fluoroscopically guided genicular nerve radiofrequency ablation for the treatment of chronic knee pain due to osteoarthritis: a systematic review. Am J Phys Med Rehabil. 2022 May 1;101(5):482-92.[Abstract]
247. Li G, Zhang Y, Tian L, et al. Radiofrequency ablation reduces pain for knee osteoarthritis: a meta-analysis of randomized controlled trials. Int J Surg. 2021 Jul;91:105951.[Abstract][Full Text]
248. Tan YL, Neo EJR, Wee TC. Ultrasound-guided genicular nerve blockade with pharmacological agents for chronic knee osteoarthritis: a systematic review. Pain Physician. 2022 Jul;25(4):E489-502.[Abstract][Full Text]
249. Liu J, Wang T, Zhu ZH. Efficacy and safety of radiofrequency treatment for improving knee pain and function in knee osteoarthritis: a meta-analysis of randomized controlled trials. J Orthop Surg Res. 2022 Jan 15;17(1):21.[Abstract][Full Text]
250. Chen AF, Mullen K, Casambre F, et al. Thermal nerve radiofrequency ablation for the nonsurgical treatment of knee osteoarthritis: a systematic literature review. J Am Acad Orthop Surg. 2021 May 1;29(9):387-96.[Abstract]
251. Guevara-Noriega KA, Chavez-Abiega R, Castro-Rios JG. Embolization of genicular arteries in patients with knee osteoarthritis as an alternative for refractory pain treatment: a systematic review. [in spa]. Med Clin (Barc). 2022 Dec 23;159(12):592-7.[Abstract]
252. Epelboym Y, Mandell JC, Collins JE, et al. Genicular artery embolization as a treatment for osteoarthritis related knee pain: a systematic review and meta-analysis. Cardiovasc Intervent Radiol. 2023 Jun;46(6):760-9.[Abstract]
253. Lange B, von Zabern D, Elling C, et al. Efficacy and safety of tapentadol prolonged release for moderate-to-severe chronic osteoarthritis knee pain: a pooled analysis of two double-blind, randomized, placebo- and oxycodone controlled release-controlled studies. Curr Med Res Opin. 2017 Aug;33(8):1413-22.[Abstract]
254. Jurgensmeier K, Jurgensmeier D, Kunz DE, et al. Intra-articular injections of the hip and knee with triamcinolone vs ketorolac: a randomized controlled trial. J Arthroplasty. 2021 Feb;36(2):416-22.[Abstract]
255. Bellamy JL, Goff BJ, Sayeed SA. Economic impact of ketorolac vs corticosteroid intra-articular knee injections for osteoarthritis: a randomized, double-blind, prospective study. J Arthroplasty. 2016 Sep;31(9 Suppl):293-7.[Abstract]
256. Ha CW, Cho JJ, Elmallah RK, et al. A multicenter, single-blind, phase IIa clinical trial to evaluate the efficacy and safety of a cell-mediated gene therapy in degenerative knee arthritis patients. Hum Gene Ther Clin Dev. 2015 Jun;26(2):125-30.[Abstract]
257. Kim MK, Ha CW, In Y, et al. A multicenter, double-blind, phase III clinical trial to evaluate the efficacy and safety of a cell and gene therapy in knee osteoarthritis patients. Hum Gene Ther Clin Dev. 2018 Mar;29(1):48-59.[Abstract]
258. Borakati A, Mafi R, Mafi P, et al. A systematic review and meta-analysis of clinical trials of mesenchymal stem cell therapy for cartilage repair. Curr Stem Cell Res Ther. 2018 Feb 23;13(3):215-25.[Abstract]
259. Huang R, Li W, Zhao Y, et al. Clinical efficacy and safety of stem cell therapy for knee osteoarthritis: a meta-analysis. Medicine (Baltimore). 2020 Mar;99(11):e19434.[Abstract][Full Text]
260. Ha CW, Park YB, Kim SH, et al. Intra-articular mesenchymal stem cells in osteoarthritis of the knee: a systematic review of clinical outcomes and evidence of cartilage repair. Arthroscopy. 2019 Jan;35(1):277-288.e2.[Abstract]
261. Kim SH, Ha CW, Park YB, et al. Intra-articular injection of mesenchymal stem cells for clinical outcomes and cartilage repair in osteoarthritis of the knee: a meta-analysis of randomized controlled trials. Arch Orthop Trauma Surg. 2019 Jul;139(7):971-80.[Abstract]
262. Di Matteo B, Anzillotti G, Gallese A, et al. Placenta-derived products demonstrate good safety profile and overall satisfactory outcomes for treating knee osteoarthritis: a systematic review of clinical evidence. Arthroscopy. 2023 Aug;39(8):1892-904.[Abstract]
263. Colombini A, Libonati F, Lopa S, et al. Autologous chondrocyte implantation provides good long-term clinical results in the treatment of knee osteoarthritis: a systematic review. Knee Surg Sports Traumatol Arthrosc. 2023 Jun;31(6):2338-48.[Abstract]
264. Wiggers TG, Winters M, Van den Boom NA, et al. Autologous stem cell therapy in knee osteoarthritis: a systematic review of randomised controlled trials. Br J Sports Med. 2021 Oct;55(20):1161-9.[Abstract][Full Text]
265. Smith C, Patel R, Vannabouathong C, et al. Combined intra-articular injection of corticosteroid and hyaluronic acid reduces pain compared to hyaluronic acid alone in the treatment of knee osteoarthritis. Knee Surg Sports Traumatol Arthrosc. 2019 Jun;27(6):1974-83.[Abstract]
266. Baria MR, Vasileff WK, Borchers J, et al. Treating knee osteoarthritis with platelet-rich plasma and hyaluronic acid combination therapy: a systematic review. Am J Sports Med. 2022 Jan;50(1):273-81.[Abstract][Full Text]
267. Zhao J, Liang G, Han Y, et al. Combination of mesenchymal stem cells (MSCs) and platelet-rich plasma (PRP) in the treatment of knee osteoarthritis: a meta-analysis of randomised controlled trials. BMJ Open. 2022 Nov 16;12(11):e061008.[Abstract][Full Text]
268. Dakin P, DiMartino SJ, Gao H, et al. The efficacy, tolerability, and joint safety of fasinumab in osteoarthritis pain: a phase IIb/III double-blind, placebo-controlled, randomized clinical trial. Arthritis Rheumatol. 2019 Nov;71(11):1824-34.[Abstract][Full Text]
269. ClinicalTrials.gov. Search for fasinumab trials [internet publication].[Full Text]
270. American College of Rheumatology (ACR) and American Association of Hip and Knee Surgeons (AAHKS). Clinical practice guideline for the optimal timing of elective total hip or knee arthroplasty for patients with symptomatic moderate to severe osteoarthritis or osteonecrosis who have failed nonoperative therapy. Feb 2023 [internet publication].[Full Text]
271. American Academy of Orthopedic Surgeons. Treatment for shoulder OA with intact rotator cuff and severe glenoid retroversion: appropriate use criteria. Mar 2023 [internet publication].[Full Text]
272. American Academy of Orthopaedic Surgeons. Appropriate use criteria for the management of osteoarthritis of the knee (non-arthroplasty). Sep 2022 [internet publication].[Full Text]
273. Goodman SM, Springer BD, Chen AF, et al. 2022 American College of Rheumatology/American Association of Hip and Knee Surgeons guideline for the perioperative management of antirheumatic medication in patients with rheumatic diseases undergoing elective total hip or total knee arthroplasty. Arthritis Care Res (Hoboken). 2022 Sep;74(9):1399-408.[Abstract][Full Text]
274. American Academy of Orthopaedic Surgeons. Surgical management of osteoarthritis of the knee: evidence-based clinical practice guideline. Dec 2022 [internet publication].[Full Text]
275. American Academy of Orthopaedic Surgeons. Management of osteoarthritis of the knee (non-arthroplasty): evidence-based clinical practice guideline (3rd edition). Aug 2021 [internet publication].[Full Text]
276. US Department of Veterans Affairs. VA/DoD clinical practice guideline for the non-surgical management of hip & knee osteoarthritis. 2020 [internet publication].[Full Text]
277. Brosseau L, Thevenot O, MacKiddie O, et al. The Ottawa Panel guidelines on programmes involving therapeutic exercise for the management of hand osteoarthritis. Clin Rehabil. 2018 Nov;32(11):1449-71.[Abstract]
278. Qaseem A, Wilt TJ, McLean RM, et al. Noninvasive treatments for acute, subacute, and chronic low back pain: a clinical practice guideline from the American College of Physicians. Ann Intern Med. 2017 Apr 4;166(7):514-30.[Abstract][Full Text]
279. Manchikanti L, Kaye AM, Knezevic NN, et al. Responsible, safe, and effective prescription of opioids for chronic non-cancer pain: American Society of Interventional Pain Physicians (ASIPP) guidelines. Pain Physician. 2017 Feb;20(2s):S3-S92.[Abstract][Full Text]
280. Quinn RH, Murray J, Pezold R, et al. Management of osteoarthritis of the hip. J Am Acad Orthop Surg. 2018 Oct 15;26(20):e434-6.[Abstract][Full Text]
281. Manchikanti L, Abdi S, Atluri S, et al. An update of comprehensive evidence-based guidelines for interventional techniques in chronic spinal pain. Part II: guidance and recommendations. Pain Physician. 2013 Apr;16(2 suppl):S49-283.[Abstract][Full Text]
282. Bannuru RR, Osani MC, Vaysbrot EE, et al. OARSI guidelines for the non-surgical management of knee, hip, and polyarticular osteoarthritis. Osteoarthr Cartil. 2019 Nov;27(11):1578-89.
283. Haanen J, Obeid M, Spain L, et al. Management of toxicities from immunotherapy: ESMO clinical practice guideline for diagnosis, treatment and follow-up. Ann Oncol. 2022 Dec;33(12):1217-38.[Abstract][Full Text]
284. Gwinnutt JM, Wieczorek M, Balanescu A, et al. 2021 EULAR recommendations regarding lifestyle behaviours and work participation to prevent progression of rheumatic and musculoskeletal diseases. Ann Rheum Dis. 2023 Jan;82(1):48-56.[Abstract][Full Text]
285. Uson J, Rodriguez-García SC, Castellanos-Moreira R, et al. EULAR recommendations for intra-articular therapies. Ann Rheum Dis. 2021 Oct;80(10):1299-305.[Abstract][Full Text]
286. Fernandes L, Hagen KB, Bijlsma JW, et al; European League Against Rheumatism (EULAR). EULAR recommendations for the non-pharmacological core management of hip and knee osteoarthritis. Ann Rheum Dis. 2013;72:1125-1135.[Abstract]
287. Felson DT, Zhang Y, Anthony JM, et al. Weight loss reduces the risk for symptomatic knee osteoarthritis in women. The Framingham Study. Ann Intern Med. 1992 Apr 1;116(7):535-9.[Abstract]
288. Zhang R, Guo H, Yang X, et al. Potential candidate biomarkers associated with osteoarthritis: evidence from a comprehensive network and pathway analysis. J Cell Physiol. 2019 Aug;234(10):17433-43.[Abstract]
289. Ren G, Krawetz RJ. Biochemical markers for the early identification of osteoarthritis: systematic review and meta-analysis. Mol Diagn Ther. 2018 Dec;22(6):671-82.[Abstract]
Key Articles
Other Online Resources
Referenced Articles
Guidelines
Diagnostic
Summary
Evidence-based imaging recommendations for patients with chronic extremity joint pain/suspected inflammatory arthritis, crystalline arthritis, or erosive osteoarthritis.Published by
American College of Radiology
Published
2022
Summary
Evidence based imaging recommendations for patients with chronic hip pain.Published by
American College of Radiology
Published
2022
Summary
Evidence-based recommendations for the use of imaging in the clinical management of OA.Published by
European League Against Rheumatism
Published
2017
Summary
Diagnosis of OA is clinical if the patient is >45 years of age, has activity-related joint pain, and has either no morning joint-related stiffness or morning stiffness that lasts no longer than 30 minutes.Published by
National Institute for Health and Care Excellence (UK)
Published
2022
Treatment
Summary
Evidence-based and consensus recommendations for the optimal timing of hip and knee arthroplasty for patients who have failed nonoperative treatment.Published by
American College of Rheumatology (ACR) and American Association of Hip and Knee Surgeons (AAHKS)
Published
2023
Summary
Recommendations on the appropriate use of treatments for shoulder osteoarthritis with intact rotator cuff and severe glenoid retroversion.Published by
American Academy of Orthopedic Surgeons
Published
2023
Summary
Recommendations to determine appropriateness of various treatments for the non-arthroplasty management of osteoarthritis of the knee.Published by
American Academy of Orthopaedic Surgeons
Published
2022
Summary
Evidence based recommendations on the perioperative management of antirheumatic medication in patients with rheumatic disease undergoing elective total hip or knee arthroplasty.Published by
American College of Rheumatology/American Association of Hip and Knee Surgeons
Published
2022
Summary
Recommendations for the surgical management of OA of the knee.Published by
American Academy of Orthopaedic Surgeons
Published
2022
Summary
Evidence-based guidelines for the medical management of OA of the knee.Published by
American Academy of Orthopaedic Surgeons
Published
2021
Summary
Consensus guideline recommendations for the use of nonpharmacologic and pharmacologic therapies in OA.Published by
American College of Rheumatology
Published
2020
Summary
Clinical practice guidelines on the management of hip and knee OA.Published by
US Department of Veterans Affairs; US Department of Defense
Published
2020
Summary
Recommends hand exercises with or without other types of interventions (i.e., orthosis and patient education) as a potentially clinically effective nonpharmacologic intervention for adults with hand OA.Published by
Ottawa Panel
Published
2018
Summary
Recommendations on noninvasive pharmacologic and nonpharmacologic treatments for low back pain.Published by
American College of Physicians
Published
2017
Summary
Guidance for the prescription of opioids for the management of chronic noncancer pain.Published by
American Society of Interventional Pain Physicians
Published
2017
Summary
Evidence-based guidelines for the management of OA of the hip.Published by
American Academy of Orthopaedic Surgeons
Published
2017
Summary
Evidence-based clinical practice guidelines for interventional techniques in the treatment of chronic spinal pain.Published by
American Society of Interventional Pain Physicians
Published
2013
Summary
Evidence-based guidelines on the management of knee OA.Published by
Osteoarthritis Research Society International
Published
2019
Summary
Consensus and evidence-based recommendations on assessment, diagnosis, and treatment of the most common and severe immunotherapy-related toxicities.Published by
European Society for Medical Oncology
Published
2022
Summary
Summary: Recommendations to guide shared decision making between people with rheumatic and musculoskeletal diseases and health professionals.Published by
European League Against Rheumatism
Published
2021
Summary
Evidence based recommendations on the use of intra-articular therapies for patients with joint synovitis, effusion and pain of different origins such as inflammatory arthritis and osteoarthritis.Published by
European League Against Rheumatism
Published
2021
Summary
Consensus recommendations on the management of knee OA.Published by
European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO)
Published
2019
Summary
Guidance on the delivery of nonpharmacologic interventions to people with hip or knee OA.Published by
European League Against Rheumatism
Published
2013
Summary
Addresses pharmacologic and nonpharmacologic management of OA.Published by
National Institute for Health and Care Excellence (UK)
Published
2022