An In-Depth Overview of Osteoarthritis

 

1. Definition
2. Pathogenesis
3. Clinical Presentation
4. Laboratory Findings and Imaging
5. Differential Diagnosis
6. Initial Treatment
7. Long-term Management Issues Including Surgery
8. Prognosis
9. Referral
10. When to Seek Referral to a Rheumatologist
11. Annotated References

 

Definition

Osteoarthritis -- known among physicians as OA -- is a disease in which cartilage breaks down. Cartilage is the spongy tissue that coats the ends of bones in joints. It acts as a shock absorber. Normally, damaged cartilage is constantly being repaired as old cartilage is degraded. When the balance between degradation and repair is thrown off, cartilage breakdown occurs. As a result of cartilage breakdown, damage to bone occurs. The result can be painful, tender, creaky joints and limitations on joint movement.

Osteoarthritis is the most common form of arthritis and affects more than 20 million Americans, mostly adults over the age of 65. It is also a leading cause of disability. By year 2020, when one out of every two Americans will be over the age of 50, the Centers for Disease Control forecast that there will be a larger increase in new cases of arthritis than of any other disease in the United States.

Pathogenesis

Pathogenesis refers to the origin and development of a disease. Understanding normal and abnormal structure and function of the joints helps us understand what goes wrong - and what might place you at risk for osteoarthritis. Although osteoarthritis is primarily a disease of the articular cartilage, damage to other supporting structures can also contribute to the acceleration of cartilage damage. This includes damage to bone ends, ligaments, the lining of the joint (synovium), and nerves that control function of the surrounding muscles, which facilitate joint movements.

Figure 1 - Diagram of Articular Cartilage structure

Cartilage is composed of collagen, proteoglycans and chondrocytes. Any abnormality in the structure of these proteins can lead to cartilage with poor function and thus to the development of osteoarthritis.

The chondrocyte manufactures building blocks such as collagen and matrix while at the same time making enzymes such as collagenase, which can destroy the cartilage. Many mediators of inflammation, called cytokines, can function to tell the chondrocyte to either make building blocks of cartilage (collagen and matrix) or enzymes (collagenase) which destroy the cartilage. What exactly controls the message to the chondrocyte is at this point an area of extensive research. However we know that, with advancing age, the chondrocyte cells appear to fail and seem to make more enzymes that destroy the cartilage resulting in osteoarthritis. In addition, trauma, even small enough to cause microfractures in the cartilage, seems to result in inflammation and acceleration of osteoarthritis.

Further, nitric oxide is produced in synovial fluid from osteoarthritic joints. Nitric oxide compromises chondrocyte survival and can damage the joint in other ways, such as by leading to suppression of glycosaminoglycan and collagen synthesis. In animal research, agents that inhibit nitric oxide synthetase diminish arthritis. Thus, treatments that block nitric oxide or nitric oxide synthetase may treat osteoarthritis in the future.

Osteoarthritis has several risk factors associated with its development, of which age is the most significant (Table 1).

Table 1: Risk Factors Associated with Osteoarthritis

Some patients with accelerated osteoarthritis have a small mutation in the gene responsible for the formation of collagen. This defect has not been found in the majority of patients with arthritis; nevertheless, surveys of large populations suggest that there may be a genetic component to another form of arthritis. Heberden's nodes (see discussion and figure 7A below) are inherited in women and are associated with primary generalized osteoarthritis. (This is a variant that involves multiple weight bearing joints in women under the age of 50.) There may be a hormonal component because estrogen replacement therapy confers a protective effect on its development in post-menopausal women.

Trauma is a risk factor for secondary osteoarthritis, especially injuries of the menisci (interarticular cartilage of crescent shape) and ligaments of the knee, as well as fractures that involve the joint. Occupational injuries are less well established as risk factors, but studies report an increased incidence of osteoarthritis among workers who use certain joints repetitively. These include: jackhammer operators (wrists, hands and elbows), coal miners, floor layers, forestry workers and farmers (knees), cotton pickers (fingers), and farmers (hips).

Recreational sports (tennis, running etc) are not associated with osteoarthritis in any age group. Indeed, by virtue of increasing muscle strength and decreasing weight, they may help prevent osteoarthritis. However a recent study looking at nurses who ran and did weight-bearing exercises seemed to show a slight increase in x-ray evidence of osteoarthritis but no increase in clinical symptoms.

Obesity in women has definitely been shown to be a risk factor for development of knee osteoarthritis. Lack of vitamin D may predispose patients with established osteoarthritis of the knee to further progression.

Clinical Presentation

The types of symptoms you have and your medical history form the clinical presentation that your doctor observes. Osteoarthritis is usually divided into two basic forms.

1. Primary or idiopathic osteoarthritis refers to the type that occurs without any underlying predisposing factor.
   
   
2. Secondary osteoarthritis follows an identifiable predisposing factor (Table 2).

More than 80% of people over the age of 50 have some evidence of osteoarthritis on x-ray, but have no symptoms.

Table 2: Prevalence of Radiographic Osteoarthritis in 3 Major Joint Sites

The joints most commonly involved are:

1. the distal (last) and proximal (middle) joint in the fingers;
2. the first carpometacarpal of the wrist(which joins the thumb to the wrist);
3. the hip,
4. the knee;
5. the cervical (neck) and lumbar (low back) spine.

Pain is the most common symptom, and it occurs primarily when the joint is moved, rarely at rest. Pain is often accompanied by crepitus (a crackling sound). Some patients experience a "gelling phenomenon" -- the perception of stiffness lasting usually less than 20 minutes in the affected joint. Why some people have pain with osteoarthritis and others do not remains unknown. The perception of pain depends not only on the disease process and the brain's processing of main messages, but also on cultural, gender, and psychological factors.

Osteoarthritis is not associated with the presence of fever, weight loss, anorexia, severe muscle atrophy, or symmetrical joint involvement. That is, when the left knee is affected, the right may not be -- in contrast to other forms of arthritis where both are apt to be affected, called symmetrical involvement.

As the disease progresses, decreased range of motion occurs because of joint destruction and increasing pain on motion. With increased inflammation in the joint, there may be accumulation of synovial fluid that distends the joint capsule, resulting in increased pain. Advanced disease is associated with deformed joints and loss of function.

Heberden's nodes are bony enlargement of the end joint of the fingers.

A similar bony enlargement of the middle finger joints is called Bouchard's node.

Heberden's Nodes

Bouchard's Nodes

First Metacarpal Joint Involvement in Osteoarthritis

Heberden's and Bouchard's nodes begin after age 45 and affect women more than men by 10 to 1. Heredity may play an important role in their development in women. Although these nodes may be inflamed and painful at the outset, most cause have pain. Nonetheless, they tend to limit motion of the joint.

Involvement of the first carpo-metacarpal joint (at the base of the thumb) (Figure 4) limits the patient's ability to open jars or use the wrist. Often this causes a deformed and "squared off" appearance to the hand.

In the foot, the most commonly involved joints are the first metatarso-phalangeal joint (first joint at the base of the great toe) which gives rise to the union in the big toe and widening of the foot. Occasionally, involvement of this joint give rise to a rigid great toe, resulting in limitation of motion and pain on walking. The patient usually finds that buying wider shoes eases discomfort. Having an Orthotic known as a "rocker bar" placed under the first joint of the great toe can be very effective in providing relief. Another commonly involved joint is the subtalar or talo-navicular joint of the ankle. This joint is responsible for inversion and eversion of the ankle. The true ankle joint, which gives us flexion of the ankle, is usually only involved if there has been damage to the ankle from trauma and/or damage to the tendons of the foot.

Hip osteoarthritis is more common in men, usually one sided, and is the cause of a painful gait. Hip pain is often "referred" and experienced as knee pain, but it can be differentiated from "true" knee pain by a simple test: motion of the hip causes knee pain, whereas knee motion does not cause knee pain.

Knee osteoarthritis is common and usually localized to one compartment of the knee. It may cause "knock knees" or "bow legs," depending on what part of the knee is damaged. Often, the most painful is osteoarthritis affecting the joint space in back of the kneecap. This may cause more pain going up and down stairs, as opposed to walking on a level surface.

Laboratory Findings and Imaging

Laboratory tests in osteoarthritis are important for the absence of any positive findings. Routine tests such as complete blood counts, urinalysis, sedimentation rate (ESR), biochemistries, and specialized tests such as rheumatoid factor and antinuclear antibody (ANA) are useful simply to exclude other diseases that cause joint pain. As we age, we sometimes develop a low level positive test for rheumatoid arthritis (rheumatoid factor) or ANA, and elevations of sedimentation rate (ESR) without obvious illness. These need not be confusing because, in arthritis, the clinical picture makes the diagnosis; lab tests tend only to confirm what your doctor already knows. The physician should never rely on laboratory tests as the sole indicator of disease when diagnosing arthritis.

Analysis of the synovial fluid removed when a joint is aspirated can be therapeutic in relieving pain and also may help confirm the diagnosis. When synovial fluid is removed, it should be cultured for bacteria and fungus as well as tested for the cell count. In osteoarthritis, the white count is usually low and the fluid is clear (like water); higher counts should suggest inflammatory arthritis or infection. The fluid may also be examined for the presence of uric acid crystals (seen in gout) or calcium pyrophosphate crystals (seen in pseudogout or chondrocalcinosis).The measurement of other biological markers is still experimental.

X-ray evaluation is the gold standard in the diagnosis of osteoarthritis. Physicians evaluate these x-rays primarily based on the amount of space in the joint. As cartilage breaks down and osteoarthritis progresses, the visual space from one bone end to another gets smaller -- a process called joint narrowing - as cartilage degenerates and disappears. In addition, x-rays may reveal osteophytes -- bony outgrowths of bone at the end of a joint that are a late sign of osteoarthritis.

Knee x-rays should always have a view taken with the patient standing, so the joint space can be seen while bearing weight. Various views are obtained to show the knee at different angles. The joint space appears clear and is a measure of the amount of cartilage left.

Figure 6 - Postero-Anterior View in full extension: Note joint space

Figure 6- Buckland-Wright View of the Same Knee: Note true joint space

Bone scans may be useful to rule out fracture due to metabolic, traumatic or metastatic (cancerous) causes of joint pain; mild increases in bone density are commonly seen in osteoarthritis. Nuclear magnetic resonance imaging (MRI) is extremely helpful in the spine and has almost replaced computerized tomography (CT) scanning and myelography in defining disc disease, tumors and spinal stenosis. MRI otherwise offers little benefit in the evaluation of primary osteoarthritis but maybe helpful in identifying other entities such as sports injuries to the menisci.

Differential Diagnosis

Many different diseases cause joint pain. Differential diagnosis is the process of how the physician figures out which one is causing your problems.

The various rheumatic diseases can be most easily classified into inflammatory and non-inflammatory categories. Patients in the former group have joint swelling and systemic (non-joint) symptoms such as morning stiffness, fatigue, fever and anemia. In the latter group, including osteoarthritis, symptoms are restricted to the joints only and consist more of joint pain than joint swelling. Osteoarthritis generally involves one or two weight-bearing joints in an asymmetric fashion, unassociated with any systemic complaints and has a gradual onset over months to years.

Rheumatoid arthritis is the illness most often confused with osteoarthritis. It tends to start at a younger age, whereas osteoarthritis rarely presents before the age of 50. Rheumatoid arthritis is the prototype of inflammatory disease, presenting with morning stiffness, fatigue, anemia, and symmetrical swollen joints. In osteoarthritis, the distal joints of the fingers are most commonly involved, whereas in rheumatoid arthritis, the middle joints of the fingers and the knuckles are most commonly involved. X-rays of patients with osteoarthritis often show osteophytes and sclerosis (increased density or whiteness) at the ends of the bones making up the joint. In rheumatoid arthritis, the pattern on x-ray is very different; the bones have a washed out appearance (osteopenia) and often show sign of erosions.

Bursitis or inflammation occurring at the bursae, which lie at the insertion of tendons to bone, can cause severe pain. But it can be differentiated from arthritis in that the joint because the joint can usually move through its normal range of motion, even thought there is pain. Although painful, bursitis generally is not a cause of disability and passes quickly. Since the joint is not involved, there is no destruction or loss of motion.

Other illnesses such as gout or pseudogout may coexist with osteoarthritis and are treated very differently. If in doubt, the physician can aspirate a small amount of synovial fluid from the joint to determine if characteristic gouty crystals are present.

Other rheumatic syndromes which are inflammatory in nature may affect the joints in an asymmetric fashion but are accompanied by systemic symptoms. These include psoriatic arthritis, Reiter's syndrome, and the arthritis of inflammatory bowel disease. However, they have other associated symptoms and clinical findings which, along with inflammation, help to differentiate them from osteoarthritis. Probably the most important entity to differentiate, which also usually affects only one joint, is septic arthritis due to bacterial infection of the joint. This requires aspiration of synovial fluid for laboratory examination. Aspiration of fluid which is cloudy with a high cell count makes the doctor immediately aware of the possibility of infection. Systemic or intravenous antibiotics should be started immediately. Any delay causes accelerated destruction of the joint with secondary osteoarthritis.

Initial Treatment

Before starting therapy, the physician must do a complete evaluation, including a medication history, medical history, and physical exam. Many patient with osteoarthritis are elderly, have co-morbid medical conditions, and take medications that may interact with those prescribed for osteoarthritis. In addition, when a complete evaluation is done by the physician, other conditions (such as cancer or thyroid disease) which may cause joint pain can be identified and treated properly.

Treatment is aimed at control of pain by decreasing inflammation in the joint, and adjuvant control with analgesics, and physical and occupational therapy modalities.

1. Non-Pharmacological Treatment

All too often, patients who receive a diagnosis of arthritis envision themselves in a wheelchair. The physician's first duty after diagnosis is education. A straightforward discussion of prognosis is always helpful, and the patient should encourage the physician to provide it. Reading material, such as disease-specific pamphlets, is available from the local chapter of the Arthritis Foundation. A list of pamphlets can also be obtained from the headquarters of the Arthritis Foundation located in Atlanta Ga. or by calling 1-800-283-7800.

Physical and occupational therapy includes exercise and physical modalities, such as the hydrocollator (a gel suspension that helps maintain moist heat on the joint), ultrasound, paraffin wax, ice packs, splints and braces. A trained physical or occupational therapist can instruct the patient on the proper use of these modalities. Exercise, including supervised fitness walking, maintains range of motion and the integrity of the supporting muscles.

In particular, quadriceps strengthening exercises reduce pain and improves function in patients with osteoarthritis of the knee.

The patient lies flat on the back with the affected leg straight and the ankle dorsiflexed to 90°, then tightens the quadriceps by pushing the back of the knee against the bed and holding it for ten seconds. This maneuver is repeated ten times, twice daily.

Figure 7A(1)

Figure 7A(2)

In addition, lying flat on the back, the patient then raises the affected leg (knee straight) ten inches off the bed and holds that position for ten seconds; this is also repeated ten times, twice daily.

Figure 7B(1)

Figure 7B(2)

Swimming techniques in which one kicks from the hips with the legs straight is another form of quadriceps strengthening. Exercise that causes more pain to the affected joint should be discontinued.

Although weight loss has only been proven to be beneficial in osteoarthritis of the knee in women, a weight loss program is essential for overall general health in overweight patients. There is no specific diet that has been proven to be efficacious in the treatment of arthritis. Nevertheless, it is important to maintain good nutrition with high calcium intake, especially in women, along with a program that keeps weight down and cholesterol under 200mg/dl.

Acupuncture is founded on naturalistic theories that are compatible with Confusianism and Taoism, and its use for relieving pain is increasing with more physicians being trained in its practice. There are some uncontrolled trials in osteoarthritis of the knee and low back pain demonstrating benefit. In addition, there is a multicenter trial under the auspices of the National Institutes of Health now in progress.

2. Pharmacological Treatment

The American College of Rheumatology has published Guidelines for the Diagnosis and Treatment of Osteoarthritis of the Hip and Knee suggesting that initial drug therapy for control of pain should begin with simple analgesics, such as acetaminophen. These early guidelines were derived from data which demonstrated that the first available non-steroidal anti-inflammatory drugs (NSAIDs), which are non-specific cyclooxygenase inhibitors, were costly in terms of side effects (gastric ulcerations, perforations and hemorrhages) and as such had no higher benefit than that provided by acetaminophen.

Professor John Vane won the Nobel prize for elucidating the mechanism of action of NSAIDs (such as aspirin and ibuprofen). They block the enzyme cyclooxygenase, which converts arachidonic acid to prostaglandin. Prostaglandin acids are short-lived substances that act as local hormones, of which prostaglandin E2 is the principal one active in inflammation. NSAIDs represent the most widely prescribed class of drugs in the world and are second only to antihypertensives in being prescribed for long periods of time in any one patient. But side effects involving the gastrointestinal, renal and hematopoietic system have limited their usefulness.

More recently, it has been discerned that two types of cyclooxygenase are blocked by NSAIDs -- COX-1, which protects the stomach, and COX-2, involved in the inflammation and pain of arthritis. Inhibition of COX-2 confers anti-inflammatory effects without inhibiting the COX-1 generated prostaglandins that are important for normal function of the stomach and platelets. Since the development of the guidelines mentioned above, new NSAIDs called COX-2 inhibitors have been developed that preferentially inhibit cyclooxygenase-2 -- thus reducing inflammation while providing superior safety profiles. These drugs now enable physicians to return to the use of anti-inflammatory medication as the first step in drug management of osteoarthritis.

Celecoxib (Celebrex) 200 mg/day and rofecoxib (Vioxx) 12.5 to 25 mg/day (Vioxx was voluntarily withdrawn by Merck from the market as of 9/30/04- see next paragraph) represented the first generation of specific COX-2 inhibitors approved for the treatment of osteoarthritis, followed by valdecoxib (Bextra), a second generation COX-2, which was also later removed from the market. Two large studies recently attempted to document superior gastrointestinal safety of the COX-2 agents, but fell short of proving the point without a doubt because of methodological problems. However, most physicians, based on these results coupled with several pre-launch safety and efficacy studies with these agents, believe in their GI safety.

Meloxicam (Mobic) is a newer non-steroidal anti-inflammatory agent with a safety profile documented to be similar to that of the specific COX-2 inhibitors. Initial drug therapy of osteoarthritis with NSAIDS is now again possible. However not all patients benefit from these drugs, and some develop side effects, including nausea, diarrhea and edema. COX-2 inhibitors do not affect platelet function and may, carefully, be used in patients taking anticoagulant drugs. Like non-selective inhibitors, selective COX-2 inhibitors may cause water retention (edema). Whether they also affect renal function in normal patients is still not known. 

The incidence of stroke, myocardial infarction, edema, hypertension and gastrointesting events with or without concomitant use of aspirin have been under continuous review by the FDA since the launch of the COX-2 inhibitors. Merck, Inc., on 9/30/04, voluntarily withdrew Vioxx from the marketplace. Their decision was based on a recent double blind 3 year study of 2600 patients who were treated with 25mg of Vioxx to prevent colonic polyps. In this cohort after 18 months of taking the medication there were close to 50% more cardiovascular events (stroke and myocardial infarct) than in the placebo group. This however only represented cardiac events in about 45 patients compared to similar events in 25 controls. Although the number of patients involved was small compared to those treated (approx 70 out of 2600) and occurred after 18 months of treatment, the company still felt obligated to withdraw the drug from the market (a responsible act based on data). Since the numbers are small, what impact this may for any indiviual patient taking Vioxx is unknown but probably small. Vioxx has a different chemical structure and metabolic breakdown products than the other COX-2 inhibitors on the market. These are (valdecoxib (Bextra), celecoxib (Celebrex) and the COX-2 selective meloxicam ( Mobic). As such, the increase in cardiovascular events should not be interpreted as a " class effect" of Cox-2 inhibitors. Meloxicam, valdecoxib and celcoxib have not been demonstrated in any clinical trials to have an increased incidence of stroke or myocardial infarct. A recently published safety trial of lumiracoxib (Prexige), another Cox-2 inhibitor in development, likewise failed to demonstrate any increase in stroke or myocardial infarct.

When long term NSAID therapy is undertaken, the patient should be monitored with certain basic tests -- at the outset and then every three to four months. These include CBC, platelet count, biochemistries, liver function and renal tests, and urinalysis.

If COX-2 inhibitors are ineffective or have to be discontinued because of side effects, then therapy can begin with simple analgesics. In addition, analgesics are excellent adjuvant therapy for patients on NSAIDs who have breakthrough pain. NSAIDS will generally work in three weeks and need not be continued if efficacy ineffective. A well-controlled trial of diclofenac plus misoprostol versus acetaminophen in patients with osteoarthritis of the hip or knee appears once again to validate the superiority of NSAIDs over simple analgesics in the treatment of osteoarthritis.

Systemic corticosteroids, either injectable or oral, have no role in the treatment of osteoarthritis. However, sometimes injections with intra-articular (into the joint) steroids for a particularly painful joint is very helpful. Never have any one joint injected more than four times per year, and each injection should result in at least three months of relief. Pain relief lasting less than two to three months should probably be considered a failure and not repeated.

Viscosupplementation is a newer therapy, proven useful in animals, that has been developed to treat patients with long-standing, painful osteoarthritis who might not be appropriate for more traditional therapy. In normal joint function, synovial fluid has the ability to change from viscous properties to elastic properties as load is increased. This is important to provide a frictionless surface. Hyaluronic acid is an important high molecular weight component of synovial fluid. Enzymes and free radicals, generated during inflammation in osteoarthritis, degrade hyaluronic acid such that it loses its viscous and elastic properties. In addition to contributing to loss of joint function, some research has postulated that the degraded hyaluronic acid in itself contributes further to joint damage. Viscosupplementation with hyaluronic acid may delay and possibly halt progression of osteoarthritis

Two viscosupplementation preparations have been approved for treatment of knee osteoarthritis in patients who have not been helped by conventional therapy or who cannot tolerate analgesics or NSAIDs. Hyalgan requires five weekly injections, while Synvisc requires three weekly injections. Both have demonstrated efficacy compared to either placebo injection with saline or treatment with NSAIDs. A new synthetic form of viscosupplementation offering one injection, with efficacy lasting up to six months, is now in phase III testing. Further work is ongoing and necessary to see if viscosupplementation can provide relief for longer than six months and if the mechanism of action is truly different than just providing excess lubricant for the joint.

3. Nutraceuticals

Since the publication of The Arthritis Cure and Maximizing the Arthritis Cure by Jason Theodosakis, M.D., the use of nutritional supplements containing glucosamine and chondroitin sulfate has sky-rocketed. Both publications claimed that these agents treat the symptoms of osteoarthritis and retard structural damage. Several European clinical trials suggested that these agents have effects in osteoarthritis similar to that of NSAIDS but with a slower onset of action. Recent meta-analyses concluded that, although the agents may show benefit, available studies provide insufficient information about the way in which they were conducted to enable definitive evaluation. A recent publication reported on a three-year study in patients with osteoarthritis of the knee randomized to either glucosamine sulfate 1500 mg per day or placebo. After three years, the patients on the glucosamine appeared not only to have clinical improvement but there was also less progression seen in the radiographs. This represents the first well-controlled study on this subject. It did not, however, look at the addition of chondroitin sulfate, which has been touted to have synergistic properties when added to glucosamine. The Office of Alternative Medicine of the National Institutes of Health has initiated a large placebo-controlled trial of glucosamine, chondroitin, and the combination of both.

S-Adenosyl-L-Methionine (SAMe), advertised as effective for osteoarthritis, is a natural compound involved in sulfuration and methylation reactions. These reactions are important in both the generation of cytokines, which affect synovial cell function, as well as reactions involved in proteoglycan synthesis. Although some animal studies are encouraging in demonstrating improvement in cartilage histology, a few short-term clinical studies have not demonstrated any superiority over standard drug therapy. Although a "natural substance," SAMe is a regulator of homocysteine metabolism and possible effects on cardiovascular disease remains an unknown possibility

One only has to remember the epidemic of eosinophilic fasciitis that occurred with widespread uses of the health-food store supplement L-tryptophan to understand the possible risk of such products. Clearly, one should not rely on anecdotal reports or testimonials for unproven remedies. Question your physician carefully about the results of any placebo-controlled clinical trials before trying any over-the-counter product or nutritional supplement. Demand clinical proof derived from a well-designed clinical trial about a product's efficacy and safety before using it. Use the Internet and this web site to review scientific studies (such as the NIH one described above), which will help to answer the questions that arise about any unproved remedy.

4. Future: Experimental Therapies

Unlike rheumatoid arthritis, the development of agents that will not only decrease symptoms but also prevent further destruction (disease modifying anti rheumatic drugs or DMARDs, also known as structural modifying anti rheumatic drugs or SMARDs) for osteoarthritis has suffered from methodological problems -- the least of which is the long time it takes for the disease to manifest itself. Nevertheless several compounds are now being tested. Anti-resorptive agents such as risedronate (Actonel) are being studied in knee osteoarthritis. Diacerein, an inhibitor of IL-1B synthesis in OA synovium has shown efficacy in European Trials and is entering phase II/III studies in the U.S.

The potential long-term treatment or cure of osteoarthritis really lies in the development of agents that reverse the balance between degradative and synthetic processes of the chondrocyte. Several possibilities are being explored. In animal studies, doxycycline inhibits cartilage collagenase activity and reduces the severity of osteoarthritis. (Although doxycycline is an antibiotic, it should not be thought that osteoarthritis is an infectious process. Rather, this research relies on other properties of doxycycline beyond its anti-infective abilities.) Transforming growth factor beta (TGFB) packaged in liposomes can repair partial thickness articular cartilage lesions in animal models. Many pharmaceutical companies are engaged in testing drugs that inhibit enzymes responsible for cartilage matrix destruction (metalloproteinase inhibitors) and block cytokines (proteins involved in the destruction). Tetracyclines are inhibitors of tissue metalloproteinases, possibly through their action on nitric oxide. This function is separate from their antimicrobial activity. A national multi-center double blind randomized placebo-controlled trial looking at disease or structural modification in obese females with knee osteoarthritis is presently in progress.

Lay press reports of cartilage transplants for traumatic osteoarthritis has excited the public. This procedure involves removing cartilage cells from a non-weight-bearing portion of the knee via the arthroscopy, growing the cells with growth factors in tissue culture, and then transplanting them back into the damaged area. Researchers have had some success repairing weight-bearing cartilage defects of less than 3 cm. When used in young patients with knee damage of less than 3 cm due to traumatic injuries, the goal is to prevent secondary osteoarthritis. However, this procedure will not rejuvenate an end-stage osteoarthritic knee.

Figure 8- Gene Therapy in Osteoarthritis

Gene therapy is another strategy. Genes that have either anti-arthritic or synthetic properties can be delivered into the joint via non-replicating viral vectors. Two human trials are presently underway in which a retrovirus is used to transfer human IL-1ra cDNA to the synovial lining of metacarpo-phalangeal joints of patients with rheumatoid arthritis. Although exciting and full of promise, the field of gene therapy still needs careful work and caution. In animal studies, for example, the transfer by gene therapy of TGF-B and BMP-7 to synovium and chrondroprogenitor cells resulted in death of the animals, possibly through overproduction of the proteins generated.

Long-term Management Issues Including Surgery

When conservative measures for treating osteoarthritis fail and pain in a specific joint disables an active individual, then surgery may restore patient comfort and normal activity. Keep in mind that surgery relieves pain more than it restores range of motion. Thus, the decision to undergo surgery is one more of personal wishes than of medical priorities. The best candidate for surgery is the patient who has a definite interruption in some activity of daily living (i.e. can't walk more than a block or awakens from sleep with pain in the affected joint) and who has not been helped sufficiently by exercise and drug therapy. For such patients, the result will be outstanding because they will be pain-free in the involved joint.

In hip and knee osteoarthritis for patients over the age of 50, total joint replacement is the therapy of choice. It is also called total joint arthroplasty. Two types of prostheses are available: those that are cemented into place, and those that are not cemented but have perforations into which your own bone grows to stabilize it. The decision between cemented or non-cemented prosthesis is a technical one revolving around the age of the patient, the condition of the joint, and the surgeon's experience. Since total joint replacements have a 15- to 20-year life before they fail, young patients may need two or more revisions. With each revision, the bone stock is less and the procedure more difficult. For this reason, many surgeons may suggest that younger patients undergo an osteotomy of the hip and knee before total joint arthroplasty. In this procedure, the joint is realigned to distribute weight more evenly to the remaining articular cartilage. Although the recovery period is considerably longer than that for total joint arthroplasty, this procedure generally relieves pain for up to five years and delays the need for replacement.

For the ankle, total joint replacement is not well perfected, but arthrodesis (fusing the joint) is a good procedure that limits pain by eliminating motion in the affected joint without great loss of mobility.

In the hand, involvement of the joint closest to the fingernail should not be surgically treated. If persistent mucous cysts are bothersome, they can be excised. For the carpometacarpal joint of the thumb, implants have failed, but reconstruction interposing a part of a tendon has shown remarkable results in relief of pain without loss of stability.

Total joints replacements are never stronger than the original joint. Post surgery competitive sports are not usually possible, but golf, walking, and even doubles tennis are permissible. As with all surgery, and more so with joint replacement, infection is a serious risk. However, the infection risk in the hands of a competent Orthopaedist should be less than 1% if the patient remains careful and treats the joint like a new heart valve. The total joint replacement patient should always use prophylactic antibiotics before invasive procedures such as dental work, cystoscopy, and colonoscopy (see Table 3 for examples of antibiotics used for prophylaxis for oral procedures).

Antibiotic Prophylaxis for Oral Procedures to be taken 1 hour prior to the procedure: Amoxicillin 2 grams (4 x 500 mg. tablets) For Patients Allergic to Penicillin, one of the following: Clindamycin (Cleocin, and others) 600 mg. Cephalexin (Keflex) 2 grams Azithromycin (Zithromax) 600 mg. Clarithromycin (Biaxin) 500 mg. Adapted from The Medical Letter, 1999 Aug 27;41(1060)

Table 3 - Antibiotic Prophylaxis for Oral Procedures in Patients with Total Joint Replacements

In my opinion, your physician should refer you to an Orthopaedic surgeon who not only has specific training in joint arthroplasty but also spends the majority of his time doing only these procedures. Specialists in joint arthroplasty should be associated with medical centers that have laminar flow operating rooms or similar infection control procedures.

Prognosis

The prognosis for patients with osteoarthritis is good but depends on the joint involved and the occupation of the patient. For example, a patient with osteoarthritis of carpo-metacarpal joint of the thumb is not disabled unless he requires constant use of the hand. Disability due to advanced disease of the hip and knees in most cases responds to surgical therapy, but involvement of the spine that compresses nerves may cause neurologic damage that does not reverse even after surgical relief. Patients with a large number of osteoarthritic joints tend to experience more rapid progression to knee osteoarthritis than those with fewer joints involved, and those with bilateral knee osteoarthritis also have a fast rate of deterioration.

Although medication has not been proven to prevent progression of osteoarthritis, it controls pain and improves quality of life. Newer treatments are being tested to stop the progression of cartilage damage. Disability is uncommon, and outlook for those temporarily incapacitated is excellent with treatment.

When to Seek Referral to a Rheumatologist

Osteoarthritis is a condition that should be carefully diagnosed by the primary care physician using the guidelines outlined. Referral to a specialist (rheumatologist) may be extremely helpful to:

1. confirm a questionable diagnosis;
2. sort out causes of secondary osteoarthritis and their potential treatments;
3. initiate programs of proper physical therapy and joint protection;
4. manage complex medication problems; and
5. consult as to the type and place for surgery in the treatment plan.

After evaluation, the rheumatologist ought to refer the patient back to the primary care physician for management, with appropriate recommendations.

 

Annotated References

1. Recommendations for the medical management of osteoarthritis of the hip and knee: 2000 update. American College of Rheumatology Subcommittee on Osteoarthritis Guidelines. Arthritis Rheum. 2000 Sep;43(9):1905-15. These are the most recent recommendations of the American College of Rheumatology, the membership group of Board-certified arthritis specialists.
   
   
2. Felson DT, et al. Osteoarthritis: new insights. Part 1: the disease and its risk factors. Ann Intern Med. 2000 Oct 17;133(8):635-46 - and Part 2: treatment approaches. Ann Intern Med. 2000 Nov 7;133(9):726-37. These are the definitive findings of a recent conference of the National Institutes of Health.
   
   
3. 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. This is one of the studies providing firm evidence for the benefits of weight loss to help prevent painful symptoms if you have osteoarthritis.
   
   
4. Creamer P, Hochberg MC. Why does osteoarthritis of the knee hurt--sometimes? Br J Rheumatol. 1997 Jul;36(7):726-8. Some people with OA have pain while others do not. All the reasons remain a mystery, although this article provides some insights.
   
   
5. Kaptchuk, RJ. Acupuncture: theory, efficacy, and practice. Ann Intern Med. 2002 Mar 5;136(5):374-83. This article would be useful reading for those considering acupuncture.
   
   
6. Reginster JY, et al. Long-term effects of glucosamine sulphate on osteoarthritis progression: a randomised, placebo-controlled clinical trial. Lancet. 2001 Jan 27;357(9252):251-6. This recent study suggested that glucosamine may help slow OA progression

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posted 10/1/2004