Osteoarthritis (Disorders of the Joints and Adjacent Tissues) (Rheumatology) Part 3



The goals of the treatment of OA are to alleviate pain and minimize loss of physical function. To the extent that pain and loss of function are consequences of inflammation, of weakness across the joint, and of laxity and instability,the treatment of OA involves addressing each of these impairments. Comprehensive therapy consists of a multimodality approach including non-pharmacologic and pharmacologic elements.

Patients with mild and intermittent symptoms may need only reassurance or nonpharmacologic treatments. Patients with ongoing, disabling pain are likely to need both nonpharmaco- and pharmacotherapy.

Treatments for knee OA have been more completely evaluated than those for hip and hand OA or for disease in other joints. Thus, while the principles of treatment are identical for OA in all joints, we shall focus below on the treatment of knee OA, noting specific recommendations for disease in other joints, especially when they differ from those for disease in the knee.

NONPHARMACOTHERAPY Since OA is a mechanically driven disease, the mainstay of treatment involves altering loading across the painful joint and improving the function of joint protectors so they can better distribute load across the joint. Ways of lessening focal load across the joint include:

1. Avoiding activities that overload the joint, as evidenced by their causing pain;

2. Improving the strength and conditioning of muscles that bridge the joint, so as to optimize their function; and

3. Unloading the joint,either by redistributing load within the joint with a brace or a splint or by unloading the joint during weight bearing with a cane or a crutch.

The simplest effective treatment for many patients is to avoid activities that precipitate pain. For example,for the middle-aged patient whose long-distance running brings on symptoms of knee OA, a less demanding form of weight-bearing activity may alleviate all symptoms. For an older person whose daily constitutionals up and down hills bring on knee pain, routing the constitutional away from hills might eliminate symptoms.

Each pound of weight increases the loading across the knee three- to sixfold.Weight loss may have a commensurate multiplier effect, unloading both knees and hips. Thus, weight loss, especially if substantial, may lessen symptoms of knee and hip OA.

In hand joints affected by OA, splinting, by limiting motion, often minimizes pain for patients with involvement either in the base of the thumb or in the DIP or proximal IP joints. With an appropriate splint, function can often be preserved. Weight-bearing joints such as knees and hips can be unloaded by using a cane in the hand opposite to the affected joint for partial weight bearing.A physical therapist can help teach the patient how to use the cane optimally, including ensuring that its height is optimal for unloading. Crutches or walkers can serve a similar beneficial function.

Exercise Osteoarthritic pain in knees or hips during weight bearing results in lack of activity and poor mobility and, because OA is so common, the inactivity that results represents a public health concern, increasing the risk of cardiovascular disease and of obesity. Aerobic capacity is poor in most elders with symptomatic knee OA, worse than others of the same age.

The development of weakness in muscles that bridge osteoarthritic joints is multifactorial in etiology. First, there is a decline in strength with age. Second, with limited mobility comes disuse muscle atrophy.Third, patients with painful knee or hip OA alter their gait so as to lessen loading across the affected joint, and this further diminishes muscle use. Fourth, "arthrogenous inhibition" may occur,whereby contraction of muscles bridging the joint is inhibited by a nerve afferent feedback loop emanating in a swollen and stretched joint capsule; this prevents maximal attainment of voluntary maximal strength.Since adequate muscle strength and conditioning are critical to joint protection,weakness in a muscle that bridges a diseased joint makes the joint more susceptible to further damage and pain. The degree of weakness correlates strongly with the severity of joint pain and the degree of physical limitation. One of the cardinal elements of the treatment of OA is to improve the functioning of muscles surrounding the joint.

At least for knee OA, trials have shown that exercise lessens pain and improves physical function. Most effective exercise regimens consist of aerobic and/or resistance training, the latter of which focuses on strengthening muscles across the joint. Exercises are likely to be effective, especially if they train muscles for the activities a person performs daily. Some exercises may actually increase pain in the joint; these should be avoided,and the regimen needs to be individualized to optimize effectiveness and minimize discomfort. Range-of-motion exercises, which do not strengthen muscles, and isometric exercises that strengthen muscles, but not through range of motion,are unlikely to be effective by themselves. Isokinetic and isotonic strengthening (strengthening that occurs when a person flexes or extends the knees against resistance) have been shown consistently to be efficacious. Low-impact exercises, including water aerobics and water resistance training, are often better tolerated by patients than exercises involving impact loading, such as running or treadmill exercises. A patient should be referred to an exercise class or to a therapist who can create an individualized regimen, and then an individualized home-based regimen can be crafted.

There is no strong evidence that patients with hip or hand OA benefit from therapeutic exercise, although for any patient with OA, individualized exercise programs should be tried. Adherence to exercise over the long term is the major challenge to an exercise prescription. In trials involving patients with knee OA who are interested in exercise treatment, a third to over a half of patients stopped exercising by 6 months. Less than 50% continued regular exercise at 1 year.The strongest predictor of continued exercise in a patient is a previous personal history of successful exercise. Physicians should reinforce the exercise prescription at each clinic visit, help the patient recognize barriers to ongoing exercise, and identify convenient times for exercise to be done routinely. The combination of exercise with calorie restriction is especially effective in lessening pain.

One clinical trial has suggested that, among those with very early OA, participating in a strengthening and multimodality exercise program led to improvement in cartilage biochemistry, as evidenced by MRI imaging. There is little other evidence, however, that strengthening or other exercise has an effect on joint structure. Correction of Malalignment Malalignment in the frontal plane (varus-valgus) markedly increases the stress across the joint,which can lead to progression of disease and to pain and disability (Fig. 18-5).Correcting malalignment, either surgically or with bracing, can relieve pain in persons whose knees are maligned. Malalignment develops over years as a consequence of gradual anatomic alterations of the joint and bone, and correcting it is often very challenging.One way is with a fitted brace, which takes an often varus osteoarthritic knee and straightens it by putting valgus stress across the knee. Unfortunately, many patients are unwilling to wear a realigning knee brace; plus, in patients with obese legs, braces may slip with usage and lose their realigning effect.They are indicated for willing patients who can learn to put them on correctly and on whom they do not slip.

Other ways of correcting malalignment across the knee include the use of orthotics in footwear. Unfortunately, while they may have modest effects on knee alignment, trials have heretofore not demonstrated efficacy of a lateral wedge orthotic vs placebo wedges.

Pain from the patellofemoral compartment of the knee can be caused by tilting of the patella or patellar malalignment with the patella riding laterally (or less often, medially) in the femoral trochlear groove. Using a brace to realign the patella, or tape to pull the patella back into the trochlear sulcus or reduce its tilt, has been shown,when compared to placebo taping in clinical trials, to lessen patellofemoral pain. However, patients may find it difficult to apply tape, and skin irritation from the tape is common. Commercial patellar braces may be a solution, but they have not been tested.

While their effect on malalignment is questionable, neoprene sleeves pulled to cover the knee lessen pain and are easy to use and popular among patients. The explanation for their therapeutic effect on pain is unclear.

In patients with knee OA, acupuncture produces modest pain relief compared to placebo needles and may be an adjunctive treatment.

PHARMACOTHERAPY While nonpharmacologic approaches to therapy constitute its mainstay, pharmacotherapy serves an important adjunctive role in OA treatment. Available drugs are administered using oral, topical,and intraarticular routes.

TABLE 18-1






Up to 1 g qid

Prolongs half-life of warfarin


Take with food. High rates of gastrointestinal side effects, including ulcers and bleeding, occur. Patients at high risk for gastrointestinal side effects should also take either a proton-pump inhibitor or misoprostol.b There is an increased concern about side effects (gastrointestinal or bleeding) when taken with acetylsalicylic acid. Can also cause edema and renal insufficiency.


375-500 mg bid


1500 mg bid


600-800 mg 3-4 times a day




100-200 mg/d

High doses are associated with an increased risk of myocardial infarction and stroke. Can cause edema and renal insufficiency.



Common side effects include dizziness, sedation, nausea or vomiting, dry mouth, constipation, urinary retention, and pruritus. Respiratory and central nervous system depression can occur.


0.025-0.075% cream 3-4 times a day

Can irritate mucous membranes.

Intraarticular injections


Varies from 3 to 5 weekly

Mild to moderate pain at injection site.


injections depending on preparation

Controversy exists re: efficacy.

aNSAIDs denotes nonsteroidal anti-inflammatory drugs.

bPatients at high risk include those with previous gastrointestinal events, persons >60 years, and persons taking glucocorticoids. Trials have shown the efficacy of proton-pump inhibitors and misoprostol in the prevention of ulcers and bleeding. Misoprostol is associated with a high rate of diarrhea and cramping; therefore, proton-pump inhibitors are more widely used to reduce NSAID-related aastrointestinal symptoms.

Acetaminophen, Nonsteroidal Antiinflammatory Drugs (NSAIDs), and COX-2 Inhibitors Acetaminophen (paracetamol) is the initial analgesic of choice for patients with OA in the knee, hip,or hands. For some patients, it is adequate to control symptoms, in which case more toxic drugs such as NSAIDs can be avoided. Doses up to 1 g four times daily can be used (Table 18-1).

NSAIDs are the most popular drugs to treat osteoarthritic pain. In clinical trials, NSAIDs produce ~30% greater improvement in pain than high-dose acetaminophen. Occasional patients treated with NSAIDs experience dramatic pain relief, whereas others experience little improvement. Initially, NSAIDs should be taken on an "as needed" basis because side effects are less frequent with low intermittent doses, which may be highly efficacious. If occasional medication use is insufficiently effective, then daily treatment with NSAIDs is indicated, with an anti-inflammatory dose selected (Table 18-1). Patients should be reminded to take low-dose aspirin and NSAIDs at different times to eliminate drug interactions.

NSAIDs have substantial and frequent side effects, the most common of which is upper gastrointestinal (GI) toxicity, including dyspepsia, nausea, bloating, GI bleeding, and ulcer disease. Some 30-40% of patients experience upper GI side effects so severe as to require discontinuation of medication. Strategies to avoid or minimize the risk of NSAID-related GI side effects include:

•  Take medications after food.

•  Avoid use of two NSAIDs.

• Use a relatively safe NSAID. In terms of GI toxicity, meta-analyses have suggested that nonacetylated salicylates, ibuprofen and nabumetone,are among the safer NSAIDs; more dangerous ones include piroxicam, ketorolac,and ketoprofen.

•  For persons at high risk of GI bleeding and/or complications, prescribe a gastroprotective agent (Table 18-1).

Major NSAID-related GI side effects can occur in patients who do not complain of upper GI symptoms. In one study of patients hospitalized for GI bleeding, 81% had no premonitory symptoms.

There are other common side effects of NSAIDs, including the tendency to develop edema, because of prostaglandin inhibition of afferent blood supply to glomeruli in the kidneys and, for similar reasons, a predilection toward reversible renal insufficiency. Blood pressure may increase modestly in some NSAID-treated patients.

Alternative anti-inflammatory medications are cyclooxygenase-2 (COX-2) inhibitors.While their rate of GI side effects may be less than for conventional NSAIDs, their risk of causing edema and renal insufficiency is similar. In addition, COX-2 inhibitors, especially at high doses, increase the risk of myocardial infarction and of stroke.This is because selective COX-2 inhibitors reduce prostaglandin I2 production by vascular endothelium, but do not inhibit platelet thromboxane A2 production, leading to an increased risk of intravas-cular thrombosis.

Intraarticular Injections: Glucocorticoids and Hyaluronic Acid Since synovial inflammation is likely to be a major cause of pain in patients with OA, local anti-inflammatory treatments administered intraarticularly may be effective in ameliorating pain,at least temporarily.Glucocorticoid injections provide such efficacy, but work better than placebo injections for only 1 or 2 weeks. This may be because the disease remains mechanically driven and,when a person begins to use the joint, the loading factors that induce pain return. Glucocorticoid injections are useful to get patients over acute flares of pain and may be especially indicated if the patient has coexistent OA and crystal deposition disease, especially from calcium pyrophosphate dihydrate crystals (Chap. 19).There is no evidence that repeated glucocorticoid injections into the joint are dangerous.

Hyaluronic acid injections can be given for treatment of symptoms in knee and hip OA, but there is controversy as to whether they have efficacy vs. placebo (Table 18-1).

Optimal therapy for OA is often achieved by trial and error, with each patient having idiosyncratic responses to specific treatments. When medical therapies have failed and the patient has an unacceptable reduction in their quality of life and ongoing pain and disability,then at least for knee and hip OA, total joint arthroplasty is indicated.

SURGERY For knee OA, several operations are available. Among the most popular surgeries, at least in the United States, is arthroscopic debridement and lavage. A well-done randomized trial evaluating this operation showed that its efficacy was no greater than that of sham surgery for relief of pain or disability.There is controversy as to whether mechanical symptoms such as buckling, which are extremely common in patients with knee OA, respond to arthroscopic debridement. While buckling is usually due to muscle weakness, a history of a recent injury, along with knee catching or locking, may suggest that a meniscal tear is contributing to this symptom. In such cases arthroscopic debridement with partial menis-cal resection might be warranted.

For patients with knee OA isolated to the medial compartment, operations to realign the knee to lessen medial loading can relieve pain. These include a high tibial osteotomy, in which the tibia is broken just below the tibial plateau and realigned so as to load the lateral, nondiseased compartment, or a unicompartmental replacement with realignment. Each surgery may provide the patient with years of pain relief before they require a total knee replacement.

Ultimately,when the patient with knee or hip OA has failed medical treatment modalities and remains in pain, with limitations of physical function that compromise the quality of life, the patient should be referred for total knee or hip arthroplasty.These are highly efficacious operations that relieve pain and improve function in the vast majority of patients. Currently, failure rates are ~1% per year, although these rates are higher in obese patients.The chance of surgical success is greater in centers where at least 50 such operations are performed yearly or with surgeons who perform a similar number annually.The timing of knee or hip replacement is critical. If the patient suffers for many years until their functional status has declined substantially,with considerable muscle weakness, postoperative functional status may not improve to a level achieved by others who underwent operation earlier in their disease course.

Cartilage Regeneration Chondrocyte transplantation has not been found to be efficacious in OA, perhaps because OA includes pathology of joint mechanics, which is not corrected by chondrocyte transplants. Simi-larly,abrasion arthroplasty (chondroplasty) has not been well studied for efficacy in OA, but it produces fibrocarti-lage in place of damaged hyaline cartilage. Both of these surgical attempts to regenerate and reconstitute articular cartilage may be more likely to be efficacious early in disease when joint malalignment and many of the other noncartilage abnormalities that characterize OA have not yet developed.

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