Chapter 193 Osteoarthritis
• Clinical signs—local tenderness; soft tissue swelling; joint crepitus; bony swelling; restricted mobility; Heberden’s (proximal interphalangeal joints) or the less common Bouchard’s (distal interphalangeal joints) nodes or both; and other signs of degenerative loss of articular cartilage
Osteoarthritis (OA), or degenerative joint disease, is characterized by joint degeneration, loss of cartilage, and alterations of the subchondral bone. It is by far the most common form of arthritis. It is estimated that more than 40 million Americans have OA, and OA is believed to be responsible for 25% of all office visits to primary care physicians. Whereas 80% of persons above 50 years of age will have x-ray evidence of significant OA, only 60% will experience symptoms. Men and women are equally affected, but symptoms occur earlier and appear to be more severe in women. OA incidence increases dramatically with age and body-mass index (especially OA of the knee).1–3 Table 193-1 lists some of the diseases that are now thought to be OA of specific joints.
|Hands||Heberden’s and Bouchard’s nodes|
|Hip||Malum coxae senilis|
|Temporomandibular joint||Costen’s syndrome|
|Spine||Ankylosing hyperostosis (interstitial skeletal hyperostosis)|
The weight-bearing joints and peripheral and axial articulations are the joints principally affected by the degenerative changes associated with OA. Much destruction of hyaline cartilage occurs, followed by hardening and the formation of large bone spurs (calcified osteophytes) in the joint margins. Pain, deformity, and limitation of joint motion result from this degeneration. Inflammation is usually minimal.
OA is divided into two categories, primary and secondary.4 In primary OA, the degenerative “wear-and-tear” process occurs after the fifth and sixth decades, with no apparent predisposing abnormalities. The cumulative effects of decades of use lead to degenerative changes by stressing the collagen matrix of the cartilage. Damage to the cartilage results in the release of enzymes that destroy collagen components. With aging, the ability to restore and synthesize normal collagen structures decreases.
One of the most interesting clinical features of OA is the lack of correlation between its severity as determined by a radiograph and the degree of pain. In some cases the joint appears normal, with little if any joint-space narrowing, yet the pain can be excruciating. Conversely, there are cases in which there is tremendous deformity yet little if any pain. In fact, about 40% of individuals with the worst x-ray classification for OA are pain-free.5 The exact cause of the pain in OA is still not well defined, but there are numerous potential causes (Box 193-2). Depression and anxiety appear to increase the experience of the pain of OA.
The onset of OA can be subtle. Morning joint stiffness is often the first symptom. As the disease progresses, pain on motion of the involved joint is worsened by prolonged activity and relieved by rest. There are usually no obvious signs of inflammation.
The specific clinical picture varies with the joint involved. Disease of the hands leads to pain and limitation of use. Knee involvement produces pain, swelling, and instability. OA of the hip causes local pain and a limp. Spinal OA (which is common) may result in compression of nerves and blood vessels, causing pain and vascular insufficiency.
The classic presentation of OA is easy to distinguish from other arthritides, especially rheumatoid arthritis, which is usually associated with much more inflammation of surrounding soft tissues. After a detailed medical history and physical examination, the best diagnostic tool to confirm the diagnosis of OA is a radiograph of the suspected joint. The classic finding in joints affected with OA is joint-space narrowing, loss of cartilage, and the presence of bone spurs (osteophytes). Box 193-3 lists important causes of the misdiagnosis of OA.
Data collected from the earliest lesions to the most advanced stages of clinical OA suggest that the cellular and tissue response is purposeful and aimed at repair of the anatomic defects. The process contributing to OA appears to be arrestable and sometimes reversible. The major therapeutic goal should be to ultimately enhance repair of the collagen matrix and regeneration by the connective tissue cells.6,7
Several studies have attempted to determine the “natural course” of OA.7,8 One group of researchers studied the course of OA of the hip over a 10-year period. All subjects had pseudocystic changes suggestive of advanced OA, yet the researchers reported marked clinical improvement and radiologic recovery of the joint space in 14 of 31 hips.8 The authors purposely applied no therapy and regarded their results as reflecting the natural course of the disease. These results, as well as others, raise the serious concern that medical intervention may actually promote disease progression.
Nonsteroidal antiinflammatory drugs (NSAIDs) have become the main treatment of OA in conventional medicine. Although these drugs provide short-term symptomatic relief, they may actually increase the rate of degeneration of the joint cartilage. Experimental studies have shown that aspirin and other NSAIDs inhibit collagen matrix synthesis and accelerate the destruction of cartilage.9 Some retrospective clinical studies have shown that NSAID use is associated with acceleration of OA and increased joint destruction.10–13 Simply stated, NSAIDs appear to suppress the symptoms but accelerate the progression of OA. Furthermore, a patient is unlikely to die from OA, but NSAID use is associated with significant risk for mortality. With older NSAIDs the risk is primarily related to gastrointestinal bleeding, whereas the newer cyclooxygenase-2 (COX-2) inhibitors celecoxib (Celebrex) and rofecoxib (Vioxx) were associated with an increase in cardiovascular events.
Skewed musculoskeletal dynamics play a role in abnormally stressing involved joints. Despite this relatively simple concept, it is only recently that this idea has been researched. An 18-month study of 230 patients with tibiofemoral osteophytes and at least some difficulty with knee-requiring activity revealed conclusively that patients with varus alignment had a fourfold increased risk of medial OA progression.14 Similarly, those with valgus alignment showed almost five times the risk of lateral OA progression. Not surprisingly, these researchers learned that the decline was greater for those with more extensive misalignments. This clearly documents the importance of considering musculoskeletal dynamics in evaluating any subject presenting with OA. Those with misalignments may have to consider manual manipulation therapies, orthotics, and extremity adjustments, along with techniques such as regular massage therapy, to relax hypertonic muscles. From a prevention standpoint, assessing and treating younger individuals may also decrease the risk of OA later in life.
In addition to addressing alignment issues, various physical therapy modalities (e.g., exercise, heat, cold, diathermy, ultrasound) are often beneficial in improving joint mobility and reducing pain in OA, especially when administered regularly (Box 193-4). Much of the benefit of physical therapy is thought to be due to achieving proper hydration within the joint capsule.
Clinical and experimental studies seem to indicate that short-wave diathermy may be of the greatest benefit.15–17 Combining short-wave diathermy therapy with periodic ice massage, rest, and appropriate exercises appears to be the most effective approach. Ultrasound and laser therapy have also been shown to be helpful.18,19
The best exercises are isometrics and swimming. These types of exercises increase circulation to the joint and strengthen surrounding muscles without placing excess strain on joints. Increasing quadriceps strength has been shown to improve the clinical features and reduce pain in OA of the knee.20 Walking programs help to improve functional status and also relieve pain in patients with OA of the knee.21Patient-specific physical therapies may be useful as well. For example, four older adults with hand OA benefited from keyboard playing for 20 minutes a day, 4 days a week.22
Dietary therapy primarily involves the achievement of normal body weight and improved insulin sensitivity, since excess weight means increased stress on weight-bearing joints affected with OA. Obesity is a major risk factor for OA of the knee, and there is also considerable evidence linking OA to the metabolic syndrome owing to the negative effects that insulin resistance, inflammatory adipokines, and other features of this syndrome have on inflammation and joint structures.23 Insulin stimulates chondrocytes to increase the synthesis and assembly of proteoglycans. Because the most prominent early change seen in the articular cartilage in OA is a decrease in both proteoglycan content and state of aggregation, insulin insensitivity or deficiency predisposes to OA.
Weight reduction, possibly due to a combination of mechanical and physiologic factors, reduces the risk for OA and has also been shown to reduce pain and improve cartilage function in existing OA, especially when combined with exercise.3,24–26,27 Lack of exercise decreases the hydration of the joint cartilages and retards diffusion of nutrients into the affected area. When OA pain develops, sufferers often tend to reduce activity, which in turn decreases muscle strength. Greater muscle weakness increases joint wear, and the inactivity can lead to weight gain, which can exacerbate OA, causing this cycle to repeat itself. In addition, patients with diabetes and cardiovascular concerns may also increase their risks for these illnesses as exercise diminishes. Weight loss and exercise have independently been effectively used to decrease the causative factors of OA and produce clinical improvement, but best results are achieved by a combined approach. One study involved 252 obese elderly patients with a body-mass index of greater than 28 and radiographically confirmed OA who were randomized into healthy-lifestyle (control), diet-only, exercise-only, and diet-plus-exercise groups.26 The exercise program involved hour-long sessions focusing on aerobics and resistance training three times a week. The goal of the dietary interventions was an average weight loss of 5% during the 18-month period. The most benefit was demonstrated in the diet-plus-exercise group. Compared with control patients and the diet-only group, subjects in the diet-plus-exercise group experienced a significant improvement in self-reported physical function, 6-minute walking distance, stair-climb times, and knee pain scores. Improvements in the exercise-only group were limited to the 6-minute walk distance.
In general, the principles detailed in Chapter 44 are appropriate for OA. Otherwise, the “Mediterranean diet” seems prudent. Typically this diet comprises abundant plant foods (including fruits, vegetables, whole-grain cereals, beans, nuts, and seeds); minimally processed seasonally fresh and locally grown foods; fish and poultry; olive oil as the main source of lipid; with dairy products, red meat, and wine in low to moderate amounts. Thus, the diet is rich in long-chain omega-3 polyunsaturated fatty acids and oleic acid (omega-9 monounsaturated), antioxidant nutrients, and unrefined carbohydrates. The Mediterranean diet has show significant effects in rheumatoid arthritis in two recent studies and may show similar benefit in OA.28,29
One popular dietary practice in the treatment of OA, conceived by Childers, a horticulturist, is the elimination of foods from the family Solanaceae (nightshade family). Childers arrived at this method after finding that this simple dietary elimination cured his own OA.30 Childers developed a theory that genetically susceptible individuals might develop arthritis and other complaints from long-term low-level consumption of the Solanum alkaloids found in tomatoes, potatoes, eggplant, peppers, and tobacco. Presumably these alkaloids inhibit normal collagen repair or promote inflammatory degeneration of the joints. Although as yet unproved, this diet has been of benefit to some individuals.
Because Americans spend more on natural remedies for OA than for any other medical condition,31 both the practitioner and the OA sufferer should be well informed about the clinical indications for these supplements.32 Many botanical and nutritional supplements are not evaluated for quality control, so it is imperative that only reputable and independently verified products be used in order to gain the desired therapeutic effect.
Glucosamine sulfate has emerged as the most popular nutritional approach to OA. It is a simple molecule composed of glucose and an amine. Its main physiologic effect on joints is to stimulate the manufacture of glycosaminoglycans (GAGs). Glucosamine also promotes the incorporation of sulfur into cartilage. It appears that as some people age, they lose the ability to manufacture sufficient levels of glucosamine. The result is that cartilage loses its gel-like nature and ability to act as a shock absorber. The inability to manufacture glucosamine may be the major factor leading to OA. Extensive preclinical and clinical research, including long-term double-blind studies, support a rationale and role for glucosamine as a major consideration in the treatment of OA. This research and the clinical benefits of glucosamine sulfate in the treatment of OA are fully described in Chapter 94.
Chondroitin sulfate, as well as shark cartilage, bovine cartilage extracts, and sea cucumber, contains a mixture of intact or partially hydrolyzed GAGs of molecular weights ranging from 14,000 to more than 30,000. Chondroitin sulfate is composed of repeating units of derivatives of glucosamine sulfate with attached sugar molecules. Although the absorption rate of glucosamine sulfate is 90% to 98%, the absorption of intact chondroitin sulfate is estimated to be anywhere from 0% to 13%.33,34 The difference in absorption is largely due to the difference in size. Chondroitin sulfate is at least 50 to 300 times larger than glucosamine sulfate, too large to pass the normal intact intestinal barrier. If chondroitin sulfate molecules were absorbed intact or partially digested, they would still be unlikely to produce any significant benefit, as the chondroitin sulfate molecules are too large to be delivered to cartilage cells. Furthermore, in patients with OA, levels of chondroitin sulfate in the synovial tissues are typically elevated.35 These absorption problems suggest that any direct effect of these compounds in OA is highly unlikely. However, conflicting evidence supports the notion that exogenous chondroitin sulfate is indeed absorbed as a high-molecular-weight polysaccharide together with derivatives originating from a partial depolymerization, desulfatation, or both.36–38
Most likely any clinical benefit from chondroitin sulfate is due to the absorption of sulfur or smaller GAG molecules broken down by the digestive tract. However, even this is controversial, because in one human study, 1 g of chondroitin sulfate failed to increase serum GAG concentration at all, based on a highly sensitive measure of intact or depolymerized GAG absorption. These results prompted the researchers to conclude: “We suggest that chondroprotection by orally administered chondroitin sulfate is a biologically and pharmacologically unfounded theory.”33
Pooled literature on the biochemistry of chondroitin sulfate offers enough information to assert that neither intact nor polymerized chondroitin sulfate is absorbed by the mammalian gastrointestinal tract. Therefore, no direct action of orally administered chondroitin sulfate on cartilage or chondrocytes is possible.
Despite the unlikeliness of any direct action, two published meta-analyses indicate that chondroitin may be superior to placebo in reducing the pain of OA.32 One of these analyses may have been exaggerated by publication bias related to the manufacturer’s sponsorship. The second meta-analysis did find chondroitin to be superior to placebo in reducing the painful symptoms of OA, although these authors also called for trials of longer duration. Finally, one study using 800 mg of chondroitin sulfate for two separate periods of 3 months over 1 year did show decreased pain and improved knee function as well as a decrease in joint-space narrowing over placebo.39 This study reveals that even intermittent use of chondroitin may be effective.
The clinical studies that have been done with orally administered chondroitin sulfate demonstrate that it is less effective than glucosamine sulfate.40–45 Furthermore, there is no evidence that using both glucosamine and chondroitin together is more effective than either alone.46 In general, the more impressive results have been achieved with glucosamine sulfate. Nevertheless, given the safety record of chondroitin and the evidence of modifying joint-space pathology, chondroitin is a reasonable addition to an ostoarthritis patient’s glucosamine regimen. In addition, chondroitin sulfate may be acting in some indirect way in improving joint health.