What is degenerative joint disease

Degenerative joint disease is also known as osteoarthritis is the most common joint disorder seen in humans, affecting some 60% to 70% of adults 60 years of age and older ¹, ². Osteoarthritis is a degenerative joint disease in which the smooth cartilage that covers the bone surfaces at the joints either is injured or wears over time. In a degenerative joint disease there is a progressive deterioration of the articular cartilage with various degrees of periarticular remodeling. Synovitis usually occurs first and results in progressive degradation of the joint cartilage, sometimes leading to degeneration of the anterior cruciate ligament and subsequent instability of the joint ³.

Osteoarthritis is a complex and progressive disease resulting in damage to and loss of articular cartilage, attrition of subarticular bone, diminished joint space, formation of osteophytes, and often synovial distension and inflammation.

Risk factors include genetics, female sex, past trauma, advancing age, and obesity ⁴. As the U.S. population ages and becomes more obese, family physicians can expect to see more patients with osteoarthritis.

Among men and women, degenerative joint disease occurs most frequently in the:

• Hands (50% to 70% of cases) ⁵,
• Knee joints (25% to 40%) ⁶,
• Hip joint (10% to 20%) ⁷ and
• Upper back and shoulders (5% to 10%) ⁶.

Furthermore, osteoarthritis increases with age and obesity ⁸.

Who gets osteoarthritis ?

Osteoarthritis is more common in older people because they have been using their joints longer. Using the joints to do the same task over and over or simply using them over time can make osteoarthritis worse.

Younger people can also get osteoarthritis. Athletes are at risk because they use their joints so much. People who have jobs that require the same movement over and over are also at risk. Injuries to a joint can increase the risk of arthritis in the joint later on. Excess weight also can accelerate arthritis in the knees, hips and spine.

Degenerative joint disease causes

The exact cause isn’t known. Osteoarthritis seems to be related to the wear and tear put on joints over the years in most people. But wear and tear alone don’t cause osteoarthritis.

Injury, infection, gout, psoriasis, and other conditions can also cause arthritis of the hand.

Osteoarthritis may also be hereditary, which means it runs in families.

What happens in the degenerative joint disease ?

Normally, a smooth layer of cartilage acts as a pad between the bones of a joint. Cartilage helps the joint move easily and comfortably. In some people, the cartilage thins as the joints are used. This is the start of osteoarthritis. Over time, the cartilage wears away and the bones may rub against one another.

Bones may even start to grow too thick on the ends where they meet to make a joint, and bits of cartilage may loosen and get in the way of movement. This can cause pain, joint swelling and stiffness.

Signs and symptoms of degenerative joint disease

The most common symptom of osteoarthritis is joint pain. The pain tends to worsen with activity, especially following a period of rest; this has been called the gelling phenomenon. Osteoarthritis can cause morning stiffness, but it usually lasts for less than 30 minutes, unlike rheumatoid arthritis, which causes stiffness for 45 minutes or more.3 Patients may report joint locking or joint instability. These symptoms result in loss of function, with patients limiting their activities of daily living because of pain and stiffness.

The joints most commonly affected are the hands, knees, hips, and spine, but almost any joint can be involved. Osteoarthritis is often asymmetric. A patient may have severe, debilitating osteoarthritis of one knee with almost normal function of the opposite leg.

Hand Osteoarthritis

The three most common sites where arthritis happens in the hand are:

• At the base of the thumb, where the thumb and wrist come together (the trapeziometacarpal or basilar joint)
• At the joint closest to the fingertip (the distal interphalangeal or DIP joint)
• At the middle joint of a finger (the proximal interphalangeal or PIP joint)

All forms of hand arthritis can cause stiffness, swelling, pain, and deformity. Osteoarthritis sometimes causes bony nodules at the middle joint of the finger (Bouchard’s nodes) or at the end joint of the finger (Heberden’s nodes). Osteoarthritis at the basilar joint can cause swelling, a bump, and a deep, aching pain at the base of the thumb. Weakness of grip and pinch can make it hard to open a jar or turn a key for those with osteoarthritis.

Figure 1. Hand Osteoarthritis. (1) Heberden nodes. (2) Bouchard nodes.

Figure 2. Radiograph of a hand affected by osteoarthritis

Note: (1) Joint space narrowing, (2) osteophytes, and (3) joint destruction. Also note changes at carpometacarpal joint (4), which are very common in osteoarthritis.

Shoulder Osteoarthritis

• Pain on range of motion
• Limitation of range of motion, especially external rotation
• Crepitus on range of motion

Knee Osteoarthritis

• Pain on range of motion
• Joint effusion
• Crepitus on range of motion
• Presence of popliteal cyst (Baker cyst)
• Lateral instability
• Valgus or varus deformity

Figure 3. Radiograph of knee osteoarthritis

Note: (A) anteroposterior and (B) lateral views showing (1) Joint space narrowing and (2) Osteophyte formation.

Hip Osteoarthritis

• Pain on range of motion
• Pain in buttock
• Limitation of range of motion, especially internal rotation

Figure 4. Radiograph of hips osteoarthritis

Note: (1) Joint space narrowing and (2) osteophyte formation

Foot Osteoarthritis

• Pain on ambulation, especially at first metatarsophalangeal joint
• Limited range of motion of first metatarsophalangeal joint, hallux rigidus
• Hallux valgus deformity

Spine Osteoarthritis

• Pain on range of motion
• Limitation of range of motion
• Lower extremity sensory loss, reflex loss, motor weakness caused by nerve root impingement
• Pseudoclaudication caused by spinal stenosis

The Diagnosis of Osteoarthritis

Your doctor will ask you questions about your pain. He or she will probably ask you if your joint pain gets worse with activity and better with rest. Your doctor will examine you to see if you have trouble moving your joint. Your doctor may also order an X-ray of the joint that is causing you problems to see what is causing the pain. Blood tests can help rule out other forms of arthritis.

Because osteoarthritis is primarily a clinical diagnosis, physicians can confidently make the diagnosis based on the history and physical examination. Plain radiography can be helpful in confirming the diagnosis and ruling out other conditions.1 Advanced imaging techniques, such as computed tomography or magnetic resonance imaging, are rarely needed unless the diagnosis is in doubt and there is a strong suspicion for another etiology, such as a meniscal injury. Figures 2 through 4 show examples of radiography of the hand, hips, and knee.

How to Treat Osteoarthritis

No cure for osteoarthritis has been found. But the right plan can help you stay active, protect your joints from damage, limit injury and control pain. Your doctor will help you create the right plan for you.

• Exercising and achieving a healthy weight are generally the most important ways to treat osteoarthritis.

The goals in treating osteoarthritis are to relieve pain and restore function. Brief rest—either by changing activities or wearing a splint—can help. Soft, snug sleeves can help support a joint when rigid splints are too restrictive. Heat (for example, paraffin baths and warm compresses) can soothe the joints and help keep them mobile.

Clinical practice guidelines have been recommended by American and British specialty societies ⁹, ¹⁰.

Table 1. Summary of osteoarthritis treatment guidelines

Intervention	Current Guidelines	FDA Approval for Indicated Use	CMS Coverage	Brand Names
Glucosamine Chondroitin	ACR: Conditional recommendation against use AAOS: Recommendation against use glucosamine and chondroitin (strong)	Evidence insufficient to demonstrate reduction in risk or disease modification (2004); Unclear regarding treatment of symptoms	Not relevant (over-the-counter)
Platelet Rich Plasma	ACR: not mentioned AAOS: unable to recommend for or against growth factor injections and/or platelet rich plasma (inconclusive)	Off-label use for an FDA-approved product	CMS National Coverage Determination: covered only for certain chronic non-healing wounds
Mesenchymal Stem Cells	ACR: not mentioned AAOS: not mentioned	Not approved by the FDA	Not covered for OA National Coverage Determination for Stem Cell Transplantation
Duloxetine	ACR: has no recommendation on using Duloxetine. AAOS: not mentioned	Indicated for treatment of chronic musculoskeletal pain including discomfort from osteoarthritis and chronic lower back pain	Not found (Medicare Part D coverage is plan dependent)	Effexor Eli Lilly and Co.
Herbal blends	ACR: not mentioned AAOS: not mentioned	Not relevant	Not relevant (over-the-counter)
Topical or transdermal analgesics	ACR: conditionally recommends topical NSAIDS, topical capsaicin AAOS: not mentioned [unless the following: “We are unable to recommend for or against the use of acetaminophen, opioids, or pain patches for patients with symptomatic osteoarthritis of the knee.” (inconclusive)]	FDA approval for OA in 1988. Black box warning regarding cardiovascular effects. Capsaicin patch is FDA-approved.	Not relevant for over-the-counter products; Coverage for prescription products is plan dependent.	Capzasin (Chattem, Inc.) Salonpas® methyl­salicylate patch (Hisamatsu America, Inc.) Voltaren® Diclofenac transdermal patch (FLECTOR® IBSA Institut Biochimique SA, licensed by Alpharma Pharmaceuticals LLC, a subsidiary of Pfizer Inc) Voltaren® Gel Diclofenac topical (Endo Pharmaceuticals, Inc. in collaboration with Sandoz, a subsidiary of Novartis
Intraarticular cortico­steroids	ACR: conditionally recommends intraarticular corticosteroid injections. AAOS: unable to recommend for or against the use of intraarticular (IA) corticosteroids (inconclusive)	Approved by the FDA for intra-lesional administration	Coverage is based on reasonable and necessary in addition to any other applicable regulation and guidance.	Aristospan (Sandoz, Inc.) Depo-medrol (Pfizer/Pharmacia/Upjohn)
Intraarticular prolotherapy	Not addressed for knee OA	Injected dextrose is FDA-approved for treatment of hypoglycemia only	National noncoverage.	Abbot Labs manufactures dextrose for IV use
Acupuncture	ACR: conditionally recommends traditional Chinese acupuncture AAOS: cannot recommend using acupuncture in patients with symptomatic OAK (strong)	FDA approves acupuncture needles as medical devices	CMS National Coverage Determination (2004): not covered
Weight loss	ACR: strongly recommends weight loss (for persons who are overweight) AAOS: suggests weight loss for patients with symptomatic osteoarthritis of the knee OAK and a BMI ≥ 25. (moderate)	Not searched	Bariatric Surgery for the Treatment of Morbid Obesity Certain procedures for the treatment of obesity are covered for Medicare beneficiaries who have a BMI ≥35, have at least one co-morbidity related to obesity and have been previously unsuccessful with the medical treatment of obesity. Other Treatments for Obesity Nationally Noncovered Indications Treatments for obesity alone remain non-covered. Supplemented fasting is not covered under the Medicare program as a general treatment for obesity, with certain exceptions. Where weight loss is necessary before surgery in order to ameliorate the complications posed by obesity when it coexists with pathological conditions such as cardiac and respiratory diseases, diabetes, or hypertension (and other more conservative techniques to achieve this end are not regarded as appropriate), supplemented fasting with adequate monitoring of the patient is eligible for coverage on a case-by-case basis or pursuant to a local coverage determination. The risks associated with the achievement of rapid weight loss must be carefully balanced against the risk posed by the condition requiring surgical treatment	Not relevant
Physical therapy	ACR: conditionally recommends receiving manual therapy in combination with supervised exercise. AAOS: not found specifically on physical therapy, although there were studies presented [unless if the following: “We are unable to recommend for or against the use of physical agents (including electrotherapeutic modalities) in patients with symptomatic osteoarthritis of the knee. (inconclusive)”“We are unable to recommend for or against manual therapy in patients with symptomatic osteoarthritis of the knee. (inconclusive)”]	Not relevant	Covered under Part B subject to certain conditions and limitations
Braces and/or orthotics (orthoses or wedges)	ACR: conditionally recommends using medially directed patellar taping; wearing medially wedged insoles if a patient with OAK has lateral compartment OA, wearing laterally wedged subtalar strapped insoles if a patient with OAK have medial compartment OA; has no recommendations on wearing laterally wedged insoles and wearing knee braces. AAOS: cannot suggest that lateral wedge insoles be used for patients with symptomatic medial compartment osteoarthritis of the knee. (moderate)	Unloader braces are approved by the FDA as medical equipment [need to check orthotics]	Medicare Part B covers medically necessary arm, leg, back, and neck braces under the durable medical equipment prefabricated orthotics benefit, subject to certain conditions and limitations. Shoes and foot orthotics are covered under certain circumstances only when criteria are met.	Ortho VQ and others

Note: ACR = American College of Rheumatology; AAOS = American Academy of Orthopaedic Surgeons; OA = Osteoarthritis; OAK = Osteoarthritis Knee

[Source ¹¹]

Table 2. Treatments for Knee Osteoarthritis

Treatment	Evidence
Physical therapy and weight loss	Combination of aerobic and strength training is recommended, and weight loss if body mass index is greater than 25 kg/m2; home programs are as effective as supervised programs 12
	Ice improves range of motion and strength, but not pain 13
	There is some evidence for patellar taping or therapeutic ultrasonography to improve physical function and decrease pain 14
Pharmacotherapy	Extended-release acetaminophen, 1,300 mg three times daily, is effective and well tolerated; however, other studies show inconclusive evidence of effectiveness 15
	Glucosamine/chondroitin supplements show mixed benefit and are not recommended by the American Academy of Orthopaedic Surgeons 12
	Opioid analgesics should be used only if conservative pharmacotherapy is ineffective in patients who are not candidates for surgery 16
	Selective and nonselective nonsteroidal anti-inflammatory drugs are effective 16
Injections	Corticosteroid injections provide short-term improvements in pain and function 17
	Hyaluronic injections have questionable benefit for pain and function, and are best reserved for patients in whom first-line conservative treatments have been ineffective and who are not candidates for surgery 12
Braces, orthoses, and other therapies	Limited evidence for medial unloader valgus brace 18

[Source ¹⁹]

NONPHARMACOLOGIC

Nonpharmacologic therapy often starts with exercise. A randomized clinical trial compared supervised home-based exercise with no exercise in 786 patients with osteoarthritis of the knee. The exercise program consisted of muscle strengthening and range-of-motion exercises. The researchers found statistically significant improvements in a validated arthritis symptom score at six, 12, 18, and 24 months ²⁰.

A Cochrane review of exercise for osteoarthritis of the knee concluded that land-based exercise can result in short-term reduction of pain and improvement in physical function ²¹. A similar Cochrane review of water-based exercise for knee and hip osteoarthritis showed improvement, but the results were not as robust ²². A randomized controlled trial of 200 persons compared education by a primary care physician to exercise supervised by a physical therapist. The supervised exercise program had better short-term outcomes, but the differences were no longer noted at 36 weeks ²³.

Therapeutic ultrasound is a physical therapy modality often used in osteoarthritis treatment. A Cochrane review of this modality concluded that although statistically significant improvements were noted in visual analog pain scales following therapeutic ultrasound for knee osteoarthritis, the clinical significance of these changes is questionable ¹⁴. The authors found that the studies were underpowered to properly determine the effectiveness of therapeutic ultrasound for knee or hip osteoarthritis. A Cochrane review on transcutaneous electrical nerve stimulation found no clinically significant improvement in knee osteoarthritis pain ²⁴.

Because obesity is considered a major risk factor for osteoarthritis, studies have investigated whether weight loss improves patient outcomes. A meta-analysis of weight reduction and knee osteoarthritis concluded that weight loss of 5 percent from baseline was sufficient to reduce disability ²⁵. Additionally, pain and disability were reduced if patients lost more than 6 kg (13.2 lb) ²⁵. Aerobic exercise is important for weight loss, but can be challenging in persons with osteoarthritis of weight-bearing joints. Swimming, elliptical training, cycling, and upper body exercise may help in such cases.

Other nonpharmacologic treatments include bracing and splinting to help support painful or unstable joints. A cane can help reduce the weight load in persons with hip or knee osteoarthritis, but it needs to be properly fitted and used on the side contralateral to the affected joint ²⁶.

MEDICATIONS

Osteoarthritis symptoms, primarily pain, may be helped by certain medications, including:

• Acetaminophen. Acetaminophen (Tylenol, others) has been shown to be effective for people with osteoarthritis who have mild to moderate pain. Taking more than the recommended dosage of acetaminophen can cause liver damage.
• Nonsteroidal anti-inflammatory drugs (NSAIDs). Over-the-counter NSAIDs, including ibuprofen (Advil, Motrin IB, others) and naproxen sodium (Aleve, others), taken at the recommended doses, typically relieve osteoarthritis pain. Stronger NSAIDs, available by prescription, may also slightly reduce inflammation along with relieving pain. NSAIDs can cause stomach upset, cardiovascular problems, bleeding problems, and liver and kidney damage. Topical NSAIDs have fewer side effects and may relieve pain just as well.
• Duloxetine (Cymbalta). Normally used as an antidepressant, this medication is also approved to treat chronic pain, including osteoarthritis pain.

The mainstay of treatment for mild osteoarthritis is acetaminophen ²⁷. It is inexpensive, safe, and effective. A 2006 Cochrane review concluded that acetaminophen is better than placebo for treating mild osteoarthritis, and equal to nonsteroidal anti-inflammatory drugs (NSAIDs), but with fewer gastrointestinal adverse effects. Patients should be instructed to take 650 to 1,000 mg of acetaminophen up to four times per day to relieve osteoarthritis symptoms. The U.S. Food and Drug Administration recommends no more than 4,000 mg of acetaminophen per day to avoid liver toxicity. It further cautions patients to be aware of coincident use of other over-the-counter or prescription medications that may contain acetaminophen ²⁸.

When acetaminophen fails to control symptoms, or if symptoms are moderate to severe, NSAID therapy is recommended. NSAIDs as a class are superior to acetaminophen for treating osteoarthritis ²⁷. Patients taking NSAIDs should be cautioned about adverse effects, which may include gastrointestinal bleeding, renal dysfunction, and blood pressure elevation (number needed to harm = 12) ²⁷. There have not been many head-to-head studies comparing nonsteroidal agents, so less expensive, generic products are appropriate (e.g., ibuprofen, naproxen, diclofenac). Cyclooxygenase-2 inhibitors, such as celecoxib (Celebrex), have an improved safety profile for gastrointestinal adverse effects ²⁹, but are costly and confer an increased cardiovascular risk ³⁰. Table 3 lists medications commonly used to treat osteoarthritis, typical dosing, and relative costs.

 

Table 3. Medications Commonly Used for Osteoarthritis

Medication	Typical dosage	Cost of generic (brand)*
Acetaminophen	650 to 1,000 mg four times per day	$17 ($20)
Celecoxib (Celebrex)	200 mg per day	NA ($141)
Diclofenac sodium	50 mg two to three times per day	$46 (NA)
Diclofenac/misoprostol (Arthrotec)	50 mg/200 mcg two to three times per day	NA ($195)
Ibuprofen, over-the-counter	400 to 600 mg three times per day	$28† ($30)
Meloxicam (Mobic)	7.5 to 15 mg per day	$16† ($155)
Nabumetone	500 mg two times per day	$40 (NA)
Naproxen, over-the-counter (Aleve)	220 to 440 mg two times per day	$5 ($5)
Naproxen (Naprosyn)	250 to 500 mg two times per day	$20† ($151)
Oxaprozin (Daypro)	1,200 mg per day	$26 ($206)
Sulindac (Clinoril)	150 to 200 mg two times per day	$19 ($92‡)

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[Source ³¹]

American College of Rheumatology guidelines

The American College of Rheumatology has issued guidelines for pharmacologic treatment of osteoarthritis of the hand, hip, and knee ³².

For hand osteoarthritis, the American College of Rheumatology conditionally recommends using one or more of the following:

• Topical capsaicin
• Topical nonsteroidal anti-inflammatory drugs (NSAIDs)
• Oral NSAIDs
• Tramadol

The American College of Rheumatology conditionally recommends against using intra-articular therapies or opioid analgesics for hand osteoarthritis. For patients 75 years and older, the American College of Rheumatology conditionally recommends the use of topical rather than oral NSAIDs.

For knee osteoarthritis, the American College of Rheumatology conditionally recommends using one of the following:

• Acetaminophen
• Oral NSAIDs
• Topical NSAIDs
• Tramadol
• Intra-articular corticosteroid injections

The American College of Rheumatology conditionally recommends against using chondroitin sulfate, glucosamine, or topical capsaicin for knee osteoarthritis. The American College of Rheumatology has no recommendations regarding the use of intra-articular hyaluronates, duloxetine, and opioid analgesics.

For hip osteoarthritis, the American College of Rheumatology conditionally recommends using one or more of the following for initial management:

• Acetaminophen
• Oral NSAIDs
• Tramadol
• Intra-articular corticosteroid injections

The American College of Rheumatology conditionally recommends against using chondroitin sulfate or glucosamine for hip osteoarthritis. The ACR has no recommendation regarding the use of topical NSAIDs, intra-articular hyaluronate injections, duloxetine, or opioid analgesics.

American Academy of Orthopaedic Surgeons guidelines

A 2013 clinical practice guideline from the American Academy of Orthopaedic Surgeons recommends the following pharmacologic treatments for symptomatic osteoarthritis of the knee ³³:

• Oral NSAIDs
• Topical NSAIDs
• Tramadol

The American Academy of Orthopaedic Surgeons was unable to recommend for or against the use of the following for symptomatic knee osteoarthritis:

• Acetaminophen
• Opioids
• Pain patches
• Intra-articular corticosteroid injections
• Growth factor injections and/or platelet rich plasma

The recommendation on acetaminophen is a downgrade from the previous American Academy of Orthopaedic Surgeons guideline, and reflects the use of new criteria that resulted in the selection of only one study, which found no statistical significance or minimum clinically important improvement with acetaminophen compared with placebo.

The American Academy of Orthopaedic Surgeons does not recommend treatment with any of the following:

• Intra-articular hyaluronic acid
• Glucosamine and/or chondroitin sulfate or hydrochloride

Agency for Healthcare Research and Quality findings

A comparison of analgesics for osteoarthritis carried out by the Agency for Healthcare Research and Quality (AHRQ) found ³⁴:

• A total of 273 studies were included.
• Overall, we found no clear differences in efficacy for pain relief associated with different NSAIDs.
• Celecoxib was associated with a lower risk of ulcer complications compared to nonselective NSAIDs.
• Coprescribing of proton pump inhibitors, misoprostol and H2-antagonists reduce the risk of endoscopically detected gastroduodenal ulcers compared to placebo in persons prescribed NSAIDs.
• Celecoxib and most nonselective, nonaspirin NSAIDs appeared to be associated with an increased risk of serious cardiovascular harms. There was no clear association between longer duration of NSAID use or higher doses and increased risk of serious cardiovascular harms.
• There were no clear differences between glucosamine or chondroitin and oral NSAIDs for pain or function, though evidence from a systematic review of higher-quality trials suggests that glucosamine had some very small benefits over placebo for pain. Head-to-head trials showed no difference between topical and oral NSAIDs for efficacy in patients with localized osteoarthritis, lower risk of gastrointestinal (GI) adverse events, and higher risk of dermatological adverse events, but serious gastrointestinal (GI) and cardiovascular harms were not evaluated. No head-to-head trials compared topical salicylates or capsaicin to oral NSAIDs.

Treatment of Osteoarthritis of the Knee ³⁵:

• Home-based exercise programs and tai chi show short- to medium-term benefits for symptoms (primarily pain, function, and quality of life) but lack data on long-term benefits.
• Strength and resistance training, pulsed electromagnetic field therapy, and transcutaneous electrical nerve stimulation show mostly short-term benefits, whereas agility training shows short- and long-term benefits.
• Weight loss and general exercise programs show medium- and longterm benefits.
• Intra-articular platelet-rich plasma, balneotherapy, and whole body vibration show medium-term benefits.
• Glucosamine-chondroitin and glucosamine or chondroitin sulfate alone show medium-term benefits with no long-term benefits for pain or function.

Analgesics, NSAIDs, and COX-2 inhibitors

Begin treatment with acetaminophen for mild or moderate osteoarthritic pain without apparent inflammation. If the clinical response to acetaminophen is not satisfactory or if the clinical presentation of osteoarthritis is inflammatory, consider using an NSAID.

Use the lowest effective dose or intermittent dosing if symptoms are intermittent, then try full doses if the patient’s response is insufficient.

Topical NSAID preparations, particularly diclofenac, are available. These preparations can be particularly useful in patients with symptomatic disease that is limited to a few sites or in patients who are at increased risk for adverse events with systemic NSAIDs.

In patients with highly resistant pain, consider the analgesic tramadol. Options in patients at an elevated risk for GI toxicity from NSAIDs include the addition of a proton-pump inhibitor or misoprostol to the treatment regimen and the use of the selective cyclooxygenase (COX)-2 inhibitor celecoxib instead of a nonselective NSAID.

Duloxetine

The selective serotonin-norepinephrine reuptake inhibitor duloxetine has been found to be effective in treating osteoarthritis pain ³⁶. For example, in patients with knee osteoarthritis who had persistent moderate pain despite optimized NSAID therapy, a randomized, double-blind trial found significant additional pain reduction and functional improvement with duloxetine as compared with placebo ³⁷.

However, duloxetine was also associated with significantly more nausea, dry mouth, constipation, fatigue, and decreased appetite than placebo was ³⁷. To date, trials of duloxetine in osteoarthritis have been short in duration (10-13 weeks), and studies comparing duloxetine directly with other therapies have not been performed.

Intra-articular injections

Intra-articular pharmacologic therapy includes injection of a corticosteroid or sodium hyaluronate (ie, hyaluronic acid [HA] or hyaluronan), which may provide pain relief and have an anti-inflammatory effect on the affected joint ³⁸. Ultrasound guidance can facilitate arthrocentesis and injection and is increasingly being adopted by physicians such as rheumatologists and physiatrists for this purpose.

Corticosteroid

After the introduction of the needle into the joint and before steroid administration, aspiration of as much synovial fluid as possible should be attempted. Aspiration often provides symptomatic relief for the patient and allows laboratory evaluation of the fluid, if necessary. Infected joint fluid and bacteremia are contraindications to steroid injection.

In patients with osteoarthritic knee pain, steroid injections generally result in clinically and statistically significant pain reduction as soon as 1 week after injection. The effect may last, on average, anywhere from 4 to 6 weeks per injection, but the benefit is unlikely to continue beyond that time frame ³⁹.

However, in a randomized trial by McAlindon et al ⁴⁰ comprising 140 patients with symptomatic knee osteoarthritis with synovitis, intra-articular injections of steroid (40 mg triamcinolone, every 12 weeks for 2 years) resulted in significantly greater cartilage volume loss and no significant difference in knee pain, compared with placebo injections of saline. The authors concluded that their findings do not support the use of intra-articular steroid injections for symptomatic knee osteoarthritis ⁴⁰.

In October 2017, FDA approved triamcinolone acetonide extended-release injectable suspension (Zilretta) for intra-articular treatment of osteoarthritic knee pain. Approval was based on data from a randomized, double-blind international phase III trial in which 484 patients were treated and followed for up to 24 weeks. Patients receiving Zilretta reported a statistically significant reduction in the weekly mean of the average daily pain intensity scores (ADP) from baseline to week 12 ⁴¹.

For hip osteoarthritis, a randomized, placebo-controlled study confirmed the effectiveness of corticosteroid injection, with benefits often lasting as long as 3 months ⁴².

Some controversial evidence exists regarding frequent steroid injections and subsequent damage to cartilage (chondrodegeneration). Accordingly, it is usually recommended that no more than three injections per year be delivered to any individual osteoarthritic joint. Systemic glucocorticoids have no role in the management of osteoarthritis.

Sodium hyaluronate

Intra-articular injection of sodium hyaluronate, also referred to as viscosupplementation, has been shown to be safe and possibly effective for symptomatic relief of knee osteoarthritis ⁴³. In the United States, intra-articular sodium hyaluronates are classified as medical devices rather than as drugs ⁴⁴.

Intra-articular sodium hyaluronates approved by the FDA for the treatment of osteoarthritic knee pain include the naturally extracted, non–cross-linked sodium hyaluronate products Hyalgan ⁴⁵, Supartz, Orthovisc, and Euflexxa, as well as the cross-linked sodium hyaluronate product known as hylan G-F 20 (Synvisc).

Euflexxa is derived from a fermentation process (Streptococcus), whereas the source material for the other products listed is chicken combs. At present, no distinct advantage or disadvantage has been associated with any particular source of sodium hyaluronates.

Some differences between the viscosupplements do exist in the FDA-approved prescribing information. For example, whereas Hyalgan and Synvisc have been established as safe for repeat treatment, the safety and efficacy of other products for repeat treatment have not been established.

The exact mechanisms of action through which HAs provide symptomatic relief are unknown. Possible mechanisms include direct binding to receptors (CD44 in particular) in the synovium and cartilage that can lead to several biologic activation pathways ⁴⁶.

The HA class in general has demonstrated a very favorable safety profile for chronic pain management in knee osteoarthritis, with the most common adverse event being injection-site pain. Although any intra-articular injection (whether of HAs or of steroids) may elicit an inflammatory response and possible effusion, only the cross-linked hylan G-F 20 product has been associated with a clinically distinct acute inflammatory side effect (ie, severe acute inflammatory reaction [SAIR] or HA-associated intra-articular pseudosepsis).

Prolotherapy

In a randomized, controlled trial of 90 adults with painful knee osteoarthritis who were randomized to either dextrose prolotherapy, saline injections, or at-home exercise, the patients on prolotherapy experienced significantly greater improvement in pain, function, and stiffness over the other 2 groups. Injections were administered at 1, 5, and 9 weeks, with additional injections provided as needed at weeks 13 and 17 ⁴⁷.

Additional pharmacologic agents

Muscle relaxants may benefit patients with evidence of muscle spasm. Judicious use of narcotics (eg, oxycodone and acetaminophen with codeine) is reserved for patients with severe osteoarthritis.

Glucosamine and chondroitin sulfate have been used in Europe for many years and continue to be popular with patients worldwide. In the United States, however, the glucosamine/chondroitin arthritis intervention trial (GAIT) reported, at best, limited benefit from glucosamine (500 mg 3 times daily), chondroitin sulfate (400 mg 3 times daily), or the combination of the 2 in patients with knee osteoarthritis ⁴⁸.

In GAIT patients overall, glucosamine and chondroitin sulfate alone or in combination did not reduce pain effectively at 24 weeks, but in patients with moderate-to-severe pain at baseline, the rate of response was significantly higher with combined therapy than with placebo (79.2% vs. 54.3%) ⁴⁹. At 2 years, no treatment achieved a clinically important difference in loss of joint-space width, though treatment effects on Kellgren-Lawrence grade 2 knees showed a trend toward improvement relative to the placebo group ⁴⁸.

The AHRQ comparison found no clear difference between glucosamine or chondroitin and oral NSAIDs for relieving pain or improving function. However, the AHRQ observed that most trials showing therapeutic benefits from glucosamine used pharmaceutical-grade glucosamine that is not available in the United States, noting that the trial findings may therefore be inapplicable to currently available over-the-counter preparations.

Another agent, S-adenosylmethionine (SAM-e), is a European supplement receiving significant attention in the United States. A systematic review of SAM-e found that the evidence was inconclusive, with a number of small trials of questionable quality; the authors concluded that the effects of SAM-e on pain and function may be potentially clinically relevant but are expected to be small ⁵⁰.

Chondroprotective drugs (ie, matrix metalloproteinase [MMP] inhibitors and growth factors) are being tested as disease-modifying drugs in the management of osteoarthritis. For example, MMP-13 is specifically expressed in the cartilage of individuals with osteoarthritis but not in the cartilage of normal adults ⁵¹. German researchers reported on the synthesis and biologic evaluation of an MMP-13 selective inhibitor that has demonstrated efficacy as a disease-modifying intra-articular injection for osteoarthritis ⁵².

Other investigational agents include monoclonal antibodies that inhibit nerve growth factor (NGF), such as tanezumab. Anti-NGF agents have been shown to reduce chronic pain in patients with osteoarthritis ⁵³.

COMPLEMENTARY AND ALTERNATIVE MEDICINE

A meta-analysis on the effectiveness of acupuncture for osteoarthritis of the knee found only short-term benefit, which the authors described as clinically irrelevant ⁵⁴. Acupuncture can be of benefit in chronic low back pain, but studies do not differentiate the etiology of the back pain ⁵⁵.

Balneotherapy is a heterogeneous group of treatments also known as spa therapy or mineral baths. A Cochrane review concluded that mineral baths were of some benefit to patients with osteoarthritis, but the authors addressed methodologic flaws in the studies and urged caution in interpreting the findings ⁵⁶. Capsaicin cream is a topical analgesic derived from chili peppers. It has been found to be superior to placebo in treating osteoarthritis pain. It is widely available, is relatively inexpensive, and can be used as an adjunct to standard osteoarthritis treatments ⁵⁷. There also is evidence supporting the use of the supplement S-adenosylmethionine (SAM-e) to reduce functional limitation, but not compared with placebo in patients with osteoarthritis pain. The effectiveness of SAM-e is comparable to that of NSAIDs in some studies but with fewer adverse effects ⁵⁸.

DO NOT USE Glucosamine and Chondroitin

• Do NOT use glucosamine and chondroitin to treat patients with symptomatic osteoarthritis of the knee ⁵⁹. Both glucosamine and chondroitin sulfate do not provide relief for patients with symptomatic osteoarthritis of the knee.
• Do NOT use lateral wedge insoles to treat patients with symptomatic medial compartment osteoarthritis of the knee ⁵⁹. In patients with symptomatic osteoarthritis of the knee, the use of lateral wedge or neutral insoles does not improve pain or functional outcomes. Comparisons between lateral and neutral heel wedges were investigated, as were comparisons between lateral wedged insoles and lateral wedged insoles with subtalar strapping. The systematic review concludes that there is only limited evidence for the effectiveness of lateral heel wedges and related orthoses. In addition, the possibility exists that those who do not use them may experience fewer symptoms from osteoarthritis of the knee.

 

Physical Therapy

• Physical therapy. A physical therapist can work with you to create an individualized exercise program that will strengthen the muscles around your joint, increase your range of motion and reduce pain. Regular gentle exercise that you do on your own, such as swimming or walking, can be equally effective.
• Occupational therapy. An occupational therapist can help you discover ways to do everyday tasks or do your job without putting extra stress on your already painful joint. For instance, a toothbrush with a large grip could make brushing your teeth easier if you have finger osteoarthritis. A bench in your shower could help relieve the pain of standing if you have knee osteoarthritis.
• Tai chi and yoga. These movement therapies involve gentle exercises and stretches combined with deep breathing. Many people use these therapies to reduce stress in their lives, and research suggests that tai chi and yoga may reduce osteoarthritis pain and improve movement. When led by a knowledgeable instructor, these therapies are safe. Avoid moves that cause pain in your joints.

Mesenchymal stem cell therapy

Mesenchymal stem cell therapy continues to be a promising investigational approach to knee osteoarthritis ⁶⁰. To date there are several studies evaluating the effacy of mesenchymal stem cells in knee osteoarthritis with favorable results. However, the variability in cointerventions surrounding mesenchymal stem cell injection, including timing, frequency, culturing mode, and long-term risk warrant further research. Mesenchymal stem cells have also shown modest benefit in knee osteoarthritis after partial or complete meniscectomy in animal studies, over the short term.

SURGERY

Surgery is considered when the non-surgical options above have not helped. In most cases, you will tell your doctor when you are ready for surgery. The well-accepted indication for surgery is continued pain and disability despite conservative treatment. The goal is to restore as much function as possible and to minimize your pain. The most effective surgical intervention is total joint replacement, where the rough joint surface is removed and either replaced with your own soft tissue or with an implant. There have been excellent patient outcomes following total joint replacement of the hip, knee, and shoulder ⁶¹, ⁶². Many different prosthetic devices are available; however, controlled trials comparing the various devices are lacking. Patients can expect that most current joint prostheses will function well for 15 to 20 years ⁶².

Another type of surgery is joint fusion. The worn cartilage is removed and the bones on each side of the joint are fused together, which means that the joint will not move but it will not hurt.

There are other surgical approaches to osteoarthritis treatment, but they have not equaled the success of total joint replacement. Randomized trials of arthroscopic debridement for osteoarthritis of the knee have consistently failed to show an advantage over maximal medical therapy combined with physical therapy ⁶³.

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