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12 Articles in Volume 12, Issue #5
A-Delta Pain Fiber Nerve Conduction Study Benefits Patients With Spinal Pain
Chronic Pain Management of the Noncompliant Patient
Clinical Applications of Radiofrequency Lesioning for Back and Neck Pain
Current Understanding and Management Of Medication-overuse Headache
Fibromyalgia: An Overview of Etiology and Non-pharmaceutical Treatment Options
June 2012 Pain Research Updates
Junk The Term Narcotics—Call Them Opioids
Managing Adverse Drug Effects in Pain: Focus on Muscle Relaxants
Music Therapy for Pain Management
Perioperative Pain Management in the Opioid-tolerant Elderly Patient: Case Challenge
Practical Tips in the Treatment Of Osteoarthritis of the Knee
Sudden, Unexpected Death in Chronic Pain Patients

Practical Tips in the Treatment Of Osteoarthritis of the Knee

Recently, the American College of Rheumatology (ACR) released revised recommendations for treatment of knee osteoarthritis.1 These recommendations incorporate the latest evidence-based options for treating knee arthritis. The newly revised recommendations add to the recommendations of four other organizations that have published arthritis treatment guidelines in the last 10 years—American Academy of Orthopaedic Surgeons (AAOS),European League Against Rheumatism (EULAR),3 Osteoarthritis Research Society International (OARSI),4 and the British National Institute for Health and Clinical Excellence (NICE).5 We will highlight the common recommendations using the ACR guidelines as the standard and discuss other treatment options that are available to practitioners.

Introduction
Osteoarthritis is one of the most common causes of disability in adults. The prevalence increases with age, with a surprising 13.9% of the population over 25 years old being affected and 33.6% of the population over 65 years old affected.6

There are no specific pharmacologic treatments that prevent progression of the disease. Treatment is aimed at reducing pain and improving function. There are currently over 100 modalities described in the medical literature for treatment of osteoarthritis.

In this paper, we will use the Grades of Recommendation Assessment, Development, and Evaluation (GRADE) approach for classifying current recommendations, which is the same approach used by ACR and many other organizations.1,7-9 Using this approach, interventions will receive one of four designations: strongly recommend, conditionally recommend, conditionally not recommend, and no evidence/evidence lacking.

ACR Recommendations
The ACR divides their recommendations into pharmacologic and non-pharmacologic interventions. Separate recommendations are made for hip, knee, and hand osteoarthritis, but for the purpose of this article we will focus on knee osteoarthritis. The ACR did not make any recommendations on surgical interventions. The recommendations assume that the patient has already tried and failed intermittent over-the-counter (OTC) acetaminophen, non-steroidal anti-inflammatory drugs (NSAIDs), and nutritional aides (glucosamine, chondroitin).1

The ACR did not “strongly recommend” any medications for the initial management of knee osteoarthritis. Acetaminophen, NSAIDs (oral and topical), tramadol, and intra-articular steroids are conditionally recommended for arthritis treatment depending on the clinical scenario (Table 1). For example, patients with a history of heart disease or peptic ulcer disease may need to be selective on the type of NSAID that is used, avoiding those with higher risks.1

The ACR considers non-pharmacologic measures to be the foundation for knee osteoarthritis treatment. Land-based or aquatic exercise and weight loss (for those who are overweight) are strongly recommended to be tailored to the individual’s abilities and comorbid conditions. Self-management programs to learn more about arthritis and how to manage the disease, manual therapy with supervised exercise, psychosocial interventions, and medially directed patellar taping are conditionally recommended. There is no recommendation made for balance exercises, laterally wedged insoles, manual therapy alone, and knee braces (Table 2).1

In patients who do not desire surgical treatment or have medical conditions that preclude surgery, the ACR guidelines recommend that patients who fail initial medication management and non-pharmacologic interventions strongly consider opioid treatment following the recommended guidelines.1,10 Duloxetine (Cymbalta), transcutaneous electrical nerve stimulation (TENS), and traditional Chinese acupuncture are conditionally recommended in patients who have failed initial interventions.1

Other Treatment Options
It is recommended to use multiple modalities in treating osteoarthritis of the knee as no single modality provides complete relief of symptoms.3 Combining multiple modalities allows for synergy among the different treatments and often provides better pain relief for patients. There are six types of interventions that should be considered for the treatment of knee osteoarthritis: oral medications, injectable medications, complementary and alternative remedies, lifestyle interventions, braces/devices, and surgical therapy (Figure 1). Most of these treatments have a small to moderate impact on osteoarthritis pain; therefore, using multiple modalities makes sense in improving patients’ osteoarthritis symptoms.

Oral Medications
There is general consensus among all the guidelines that supports the use of acetaminophen, oral NSAIDs, topical NSAIDs, and tramadol.1-5 Reflecting recent warning from the FDA, the ACR cautions that if a patient is prescribed acetaminophen in the full dosage (up to 4,000 mg/d), the patient should be counseled to avoid all other products containing acetaminophen, including OTC cold remedies as well as combination products with opioid analgesics.1

Oral NSAIDs are associated with a dose-dependent risk of gastrointestinal, cardiovascular, hematologic, hepatic, and renal adverse events (AEs).11 The risk of gastrointestinal side effects can be lessened by using a cyclooxygenase (COX)-2 selective NSAID (Celebrex) or by combining non-selective NSAIDs with proton pump inhibitors.12 Concerns about cardiovascular events with COX-2 selective NSAIDs have limited the use of this class of medications in patients who have cardiovascular risk factors.13

Topical NSAIDs
Topical NSAIDs were developed to provide analgesia similar to their oral counterparts with less systemic exposure and fewer serious AEs. Topical NSAIDs have been available in Europe for the management of osteoarthritis, and both the EULAR and OARSI specify that topical NSAIDs are preferred over oral NSAIDs for patients with knee osteoarthritis of mild to moderate severity, few affected joints, and/or a history of sensitivity to oral NSAIDs.3,4 For the first time, the ACR conditionally recommends topical NSAIDs for management of knee osteoarthritis.1 Topical NSAIDs have shown promise especially for short-term pain relief (Table 3). Long term, these medications have a diminished efficacy and have the potential for systemic toxicity.14 Oral NSAIDs have recently been created with nitric oxide links to inhibit cyclooxygenase—a class of medications called cyclooxygenase-inhibiting nitric oxide donating drugs. This class of medications may show promise in the future for causing less gastric toxicity.14

Tramadol has been shown to provide pain relief and improved function in patients with osteoarthritis. It is conditionally recommended by the ACR because side effects are common.15

Injectables
Injectables provide a fairly convenient method for treatment of osteoarthritis symptoms. Compliance is good and dosing is fairly convenient. Side effects of the injectables are uncommon. As noted previously, intra-articular steroids were conditionally recommended by the ACR, whereas no recommendation was made for viscosupplementation.1

Viscosupplementation
Viscosupplementation has been shown to provide short- and moderate-term pain relief as well as improvement in function and global assessment of symptoms.16 There are few head-to-head comparison studies on the various formulations so one should be cautious in interpreting the relative value of different products. Viscosupplements have few adverse reactions. They seem to work best in patients with mild to moderate osteoarthritis with effusion. OARSI strongly recommends its use, whereas EULAR gives it a weak recommendation.3,4 The AAOS, ACR, and NICE feel there is inconclusive evidence to recommend the use of viscosupplementation.1,2,5

Complementary/Alternative Remedies
Complimentary and alternative remedies for knee osteoarthritis are a quickly expanding group of treatments that are popular with many patients. Studies done on these compounds are typically not as strong as those involving drug treatments; therefore, it is difficult to give firm recommendations for the use of many of the remedies.

Avocado/Soybean Unsaponifiable
Avocado/soybean unsaponifiables were found to improve function, pain, and global evaluation in patients with knee osteoarthritis. Side effects are reported as very minimal. Dosing is 300 to 600 mg daily, and it is reasonably cheap. The mechanism for action is thought to involve the inhibition of interleukin-1, which stimulates collagen synthesis. This potentially has a disease modifying effect but needs further study.17

Capsaicin
Capsaicin has been shown in smaller studies to provide mild to moderate relief of pain. It requires frequent dosing (3-4 applications daily), which limits its efficacy.18 It is recommended to start with low strength and small amounts to limit the initial burning quality of the product and then increase the strength and amount as tolerated by the side effects over time. It takes 2 to 3 weeks to fully get the effect of treatment. It is strongly recommended by EULAR and OARSI and weakly recommended by NICE.3-5 The ACR states there is no evidence to provide a recommendation for its use.1

Glucosamine
There are 25 studies evaluating glucosamine and osteoarthritis with mixed results. Fourteen of the 25 studies used a preparation made by Rottapharm and showed improvement in pain and function. Funnel and Egger’s plots evaluating these studies for bias showed no evidence of bias. Those studies using non-Rotta preparation showed no benefit in treatment of knee osteoarthritis.19 Two studies showed a mild effect on slowing radiologic progression of knee osteoarthritis over a 3-year period.20,21 Side effects are similar to placebo. Glucosamine is a slow-acting agent; therefore, a 3-4 month trial is recommended before deciding on efficacy. Glucosamine sulfate is recommended whereas glucosamine hydrochloride is not as it has not shown to be efficacious.19 EULAR and OARSI strongly recommend the use of glucosamine.3,4 The ACR states there is no evidence for its use and NICE and AAOS recommend against the use of glucosamine.1,2,5

Lifestyle Interventions
Lifestyle interventions provide some of the most important treatments for knee osteoarthritis frequently being equal in efficacy to other modalities and potentially providing disease-modifying effects, especially in the case of weight loss and exercise.

Thermotherapy
Thermotherapy, such as ice massage, has been shown to improve range of motion, function, and knee strength in patients with osteoarthritis, but there are only a few studies evaluating this modality.22 Thermotherapy is weakly recommended by NICE and OARSI.4,5

Balneotherapy
Balneotherapy, or mineral bath treatment, shows improved pain, quality of life, and reduced analgesic intake in several studies and meta-analyses.23 Use of mineral bath treatment is weakly recommended by OARSI.4

Braces/Devices
Braces and shoe orthoses show a small to moderate effect on pain relief although compliance with use of these modalities can be difficult.24 Braces include medial unloader braces, which take some of the weight off of the medial aspect of the knee—thought to be particularly helpful for medial compartment knee osteoarthritis. Knee sleeves are thought to provide relief by trapping heat and warming the joint. Shoe orthoses are usually used to wedge either the medial or lateral aspect of the foot and place less weight through the knee in the compartment most effected by osteoarthritis. They are strongly recommended by OARSI and weakly recommended by EULAR and ACR.1,3,4

Therapeutic Ultrasound
Therapeutic ultrasound has been shown to improve pain and function in patients with knee osteoarthritis.25 Many of the ultrasound studies are of lower quality due to the multiple methods of treatment (pulsed, continuous). Therapeutic ultrasound receives a weak recommendation by EULAR.3

Surgical Treatments (Table 4)
Arthroscopic Debridement for Knee Osteoarthritis
In 1991, Sprague first reported on arthroscopic debridement of 330 knees as a treatment option for osteoarthritis of the knee. Seventy-four percent of patients reported improved function compared to preoperative status. The author did not detail the extent of the arthritis, nor was the clinical picture associated with any kind of imaging alignment.26

Two studies published in 1991, both with a notable follow up (8+ years), reported that the best predictor of success after arthroscopic debridement for osteoarthritis was normally aligned knees with mild arthritis.27,28 These and other studies support the widely held “best practice” that arthroscopic debridement works best in patients with minimal arthritis and no angular deformity as judged by standing, long-leg radiographs.29,30

Moseley and colleagues first suggested that arthroscopic debridement for knee osteoarthritis was no better than placebo. Their study published in 2002 led the Center for Medicare and Medicaid Services to disallow the arthroscopic code for debridement in a patient with Medicare.31 This opinion has been confirmed by two more recent randomized controlled trials. One study concluded that arthroscopic debridement results are no greater than sham operations for osteoarthritis in older patients; the second study showed when evaluated with outcome scores, arthroscopic partial medial meniscectomy followed by supervised exercise was not superior to supervised exercise alone in terms of reduced knee pain, improved knee function, and improved quality of life.32,33

Another approach—seeking an answer to “when is arthroscopic partial meniscectomy (APM) helpful?”—used a mathematical model and published data combining two clinical indicators (mechanical symptoms and pain pattern) and two magnetic resonance imaging (MRI) indicators (tear type and bone marrow lesions) to help stratify patient outcome with easily obtainable clinical information.34 Their ranked response showed rank 1 (eg, displaced tear, locking, increased pain, no bone marrow lesions) represented the highest likelihood of APM benefit; rank 36 (eg, oblique tear, no mechanical symptoms, static pain, severe bone marrow lesions) represented the lowest likelihood of APM benefit. Among individuals with degenerative meniscal tears and osteoarthritis, easily obtainable clinical information can differentiate those who are more likely to benefit from APM.34

Despite these studies, arthroscopy continues to be used in the treatment of degenerative arthritis due to its low morbidity. When a patient has clinical variables suggesting mechanical symptoms, presence of an unstable meniscal, no bone marrow edema by MRI, and minimal malalignment on standing radiographs, these reported predictors improve the outcome from an arthroscopic debridement. In contrast, clearly reported predictors of poor outcomes include marked standing malalignment of the limb, restricted range of motion, prior arthroscopic debridement, and bone marrow edema on MRI.34-36

Osteotomies About the Knee
The purpose of a realignment osteotomy about an arthritic knee is to transfer weight-bearing forces from an arthritic portion of the joint to a healthier location in the joint. Osteotomies about the knee date back to the 19th century, and were an often used operation in the ’50s and ’60s.37 The use of resurfacing arthroplasty, both total knee replacement (TKA) and unicompartmental knee replacement, has reduced enthusiasm for this technically challenging operation. However, despite its rather significant decline, an osteotomy about the knee remains a viable treatment option in carefully selected patients with knee arthritis.38-41

The most common osteotomy is a high-tibial osteotomy to correct medial compartment gonarthrosis combined with genu varus knee alignment.42 (See Table 5 for patient selection.) Surgical technique requires creating a stable osteotomy site that heals without increasing deformity; this is crucial to the end result. Critical to this is the quality of the surgical technique, with exacting preoperative planning and stable intraoperative fixation. Indeed, the accuracy of postoperative alignment appears to be the primary factor in success of the operated knee over time. Despite this, appropriate postoperative alignment does vary between reports, and reports vary on whether this alignment is taken as an anatomic alignment on knee radiographs or biomechanical alignment on long-leg radiographs. However, there continues to be enthusiasm for high-tibial osteotomies, particularly in the younger patient, the heavier patient, and the patient who continues to be active in work or play.

Knee Joint Resurfacing Arthroplasty 
(Total Knees and Partial Knees)
TKA is a highly successful surgical procedure for the treatment of knee osteoarthritis. It restores mobility in many patients and leads to a better quality of life. However, we are seeing a precipitous increase in its use. In 2008, 615,050 TKAs were performed in the US adult population—134% more than in 1999. During the same time period, the overall population size increased by 11%. Though previous authors reported the increase in TKAs was a result of an aging population and growing levels of obesity,43,44 a more recent report countered this assumption.45 The authors felt that the recent increase was likely related to a multitude of factors, including a growing prevalence of sports-related knee injuries and expanded indications for TKA due to both patient and surgeon preferences.

Figure: Treatment Options for Patients with Knee Osteoarthritis

Any surgical intervention should be weighed on its possible risks and benefits compared to alternative treatments. TKA are often felt to be the “end game” treatment for knee arthritis; however, clinicians must account for the appropriateness of the procedure. It has been shown that utilization of TKA in the United States is greater than that in some European countries, despite a similar prevalence of osteoarthritis.46 This is also in spite of a lower utilization of TKA among several subpopulations within the United States, including racial minorities.47-49 By 2030, the demand for primary TKAs is projected to grow by 673% to 3.48 million procedures, and the demand for knee revisions is projected to grow by 601% between 2005 and 2030.50 This holds significance for both financial burden and manpower burden to cover this projection.

Continued research is necessary to help the clinician elucidate patient risk profile, knee outcome data across various patient profiles, and appropriate patient consultation for knee arthroplasty.

Conclusions
Knee osteoarthritis is a difficult condition to treat. The recent ACR guidelines highlight the major pharmacologic and non-pharmacologic treatments available; other international guidelines supplement these recommendations. There is good evidence for the use of medications such as acetaminophen, topical and oral NSAIDs, and tramadol; injectables including viscosupplementation and intra-articular steroids; lifestyle interventions such as education, exercise, weight loss, and mineral baths; and braces such as a knee unloader brace, knee sleeve, and shoe inserts. There are many controversial treatments needing more study. Ideally, treatment should involve the use of multiple modalities to allow for synergy of inventions. In the future, there is the potential for disease modifying interventions but none have been studied well enough to make recommendations at this time. These disease-modifying interventions would expand the nonoperative treatment options available for knee osteoarthritis.

Last updated on: June 30, 2015
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Practical Tips in the Treatment of Osteoarthritis of the Hip
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