Pathophysiology of osteoarthritis

Understanding of the causes of OA is increasing. OA affects the entire joint: hyaline cartilage is lost, bony remodeling occurs, and capsular stretching and periarticular muscle weakness occurs. It is believed to be caused by aberrant local mechanical factors, such as injury, misalignment, and muscle weakness in a joint vulnerable to degeneration because of factors such as aging and genetics. To think that OA is simply “normal wear and tear” of the cartilage is incorrect. Normal cartilage, like other tissues, becomes healthier with use. For example, some evidence in animal studies and small human studies shows that immobilization causes a decrease in cartilage volume, and exercise causes an increase in cartilage volume . However, injury to the cartilage can occur from abnormally high or repetitive loads across joints, because successive cartilage injury overwhelms the ability of the cartilage to regenerate. Once damage begins, a degenerative cascade continues, which may be partially from wear but seems to be caused more from increases in the lysosomes and matrix proteins that break down cartilage, and decreased rate in the synthesis of new proteoglycans.

Once cartilage damage occurs, other parts of the joint also become affected, and sclerosis of the bone, ligamentous laxity, and muscle weakness around the joint is seen.

High repetitive forces across a joint are a risk factor for OA. For example, a high prevalence of OA occurs in specific sites related to vocational and sports overload, such as in the ankles of ballet dancers and the elbow of baseball pitchers . However, joint malalignment, which causes excessive loading in an abnormal location, seems to be the most important risk factor for structural deterioration of the joint . For example, OA is more common after anterior cruciate ligament (ACL) tears and meniscus injuries, most likely because of changed biomechanics of the joint. OA is also more common in the weight-bearing joints of obese people, probably because of both increased joint forces and changes in biomechanics. For example, for those in the highest quintile for body mass index at a baseline examination, the relative risk for developing severe OA of the knees in the next 35 years was 1.9 for men and 3.2 for women .

It is likely that the source of pain in OA is the synovium and joint capsule (because the cartilage does not contain nociceptive fibers) . A poor correlation exists between the severity of OA as judged on radiograph and clinical symptoms. Up to 40% of those who have severe OA as judged with radiograph are symptom-free . Why some patients who have minimal imaging findings have severe pain whereas others who have severe joint degeneration have no symptoms is unclear; most likely it is a combination of local biochemical factors, central and peripheral pain processing, psychosocial issues, and other factors that are not well understood .

Diagnosis of osteoarthritis

Because of the poor correlation between imaging and symptoms, the diagnosis of OA is made on clinical grounds. Symptoms include joint pain related to activity. As the disease progresses, patients often experience pain also at night or at rest. A history of the joint giving away or feeling unstable is common.

On physical examination, usually joint-line tenderness and pain to palpation occurs in associated areas, such as over nearby bursa, muscles, and tendons. Signs of other joint degeneration often are present, such as meniscus tears and ACL tears in the knee . Often alignment issues are noted, such as varus or valgus deformities at the knee, which are strong risk factors for worsening disease and are associated with functional limitations . The muscles surrounding the joint are often weak, such as quadriceps weakness in those who have knee OA. Often balance and proprioception around the joint are abnormal. However, the remainder of the neurologic examination, such as sensation and reflexes, should be unaffected.

Treatment of osteoarthritis

Several recent meta-analyses have confirmed that exercise helps to improve strength, decrease pain, and improve function and quality of life in patients who have OA . The benefit of joint-specific strengthening seems to increase when combined with a general strengthening and flexibility program. Because aerobic exercise has also been shown to decrease pain and improve function in patients who have OA, when an exercise plan includes this, it will be most beneficial. The main drawback to exercise as a treatment for OA is that it requires continued patient effort and compliance. The beneficial effects of exercise are lost if the patient stops exercising . Because of this, physicians must try to assist patients with compliance. Studies that have looked at exercise compliance in patients who have OA have found that social support, having a partner to exercise with, organized group exercise activities, and familiarity with the task all increased compliance . Patient beliefs also strongly affect compliance, and therefore patient education is important. In one study, patients who were less compliant had more perceived symptoms, believed arthritis was caused by age or wear, and did not see physical therapy as effective .

Some evidence shows that exercise may help prevent OA or slow its progression. In one study, increased muscle mass was associated with better medial and lateral tibial cartilage volume. This relationship was significant for both muscle mass in the legs and arms . Several studies found that women who had stronger quadriceps had a reduced risk for developing hip or knee OA. This finding is believed to be because quadriceps may help absorb shock at heel strike . Knee load is also a significant factor in disease progression. Certain factors evaluated through gait analysis, such as an increased external knee adduction moment generated during walking (which forces the knee laterally into varus and compresses the medial joint compartment), have been shown to lead to accelerated progression of knee OA . Exercise may help change some of these patterns, for example through strengthening the gluteus medius to change proximal forces and training patients in different gait strategies.

Other joint-specific treatments for OA have been developed to address biomechanical forces across the symptomatic joint, including shoe modification for knee OA, the use of a cane to unload the joint in lower-extremity OA, and a variety of braces.

For treatment of OA pain, both acetaminophen and nonsteroidal anti-inflammatory drugs (NSAIDs) have been shown to be modestly effective. Because of the greater toxicity of NSAIDs, acetaminophen is usually the first medication recommended. However, in a large crossover study, patients who had been treated with NSAIDS first showed no benefit when crossed over to acetaminophen for 6 weeks . Glucosamine and chondroitin sulfate are commonly used to treat OA. The efficacy of these is unclear. Several randomized controlled trials have shown them to be helpful, but others, including large multicenter trials, have not shown them to be effective. They may be more effective for moderate to severe pain than for mild pain . Other medications have also been found effective in the treatment of OA, such as tramadol .

Intra-articular corticosteroid injections are commonly used to treat OA. Although they are administered to many joints in the body, their efficacy has been best shown in the knee. They have been found to be more efficacious than placebo for short-term pain relief (2–3 weeks), but have shown no difference for long-term pain relief .

Viscosupplementation injections are approved in the United States for knee OA; however, they are also often used to treat hip and shoulder OA. Recent meta-analyses have shown them to be effective for pain relief and to improve function, particularly 5 to 13 weeks after the injection. Risks of the procedure include a small chance of infection and an inflammatory response to the medication .

Acupuncture is another needle therapy commonly used for pain associated with OA. Sham-controlled randomized controlled trials have found this technique to be therapeutic with little risk for side effects .

Pathophysiology of tendon disease

The pathophysiology of tendon disease is not well understood. One major cause seems to be aging. As individuals age, tendon fiber content changes and tendons lose the strength and ability to regenerate and repair as quickly. The incidence of tendinopathies, such as rotator cuff and Achilles tendinopathy, increases with age . Another major factor in tendinopathies, at least in some areas of the body, seems to be overuse. This effect may be caused by repetitive microtrauma that may not allow enough time for the tendon to repair . For example, symptomatic Achilles tendinopathy is 10 times more likely in runners than nonrunners . Tendinopathies are often associated with too rapid an increase in activity; for example, a sedentary person beginning a vigorous exercise program or a runner increasing mileage and intensity too quickly. Another factor believed to influence tendinopathies is faulty biomechanics and structural deficits. For example, runners with Achilles tendinopathy are more likely to have excessive pronation, limited mobility of the subtalar joint, and limited ankle dorsiflexion .

Why some patients have pain in an area of tendon degeneration and others do not is unclear. Just as in OA, patients can show changes on imaging indicating severe disease and experience no symptoms. Sher and colleagues performed MRIs of 96 asymptomatic shoulders to determine the prevalence of rotator cuff tendon disease. They found that 34% of the asymptomatic shoulders had rotator cuff tears, including 20% with full-thickness tears. The frequency of tears increased significantly with age. In subjects older than 60 years, 54% of the asymptomatic shoulders had either full or partial rotator cuff tears. Some evidence supports that asymptomatic structural changes may become symptomatic with extensive tendon loading. Fredberg and Bolvig used ultrasound to study the Achilles and patellar tendons of elite soccer players, finding that 29% of the asymptomatic tendons showed structural changes of tendinosis at the start of the season. The players were followed up weekly, and the investigators found that those who had tendinosis changes in the patellar tendon had a 17% risk for developing symptoms of tendinopathy during the next 12-month season, and those who had tendinosis changes in the Achilles tendon had a 45% risk for developing symptomatic Achilles tendinopathy. Only one player in the normal tendon group developed symptoms during the season. Several theories exist as to why some tendinoses are painful and some are asymptomatic. One theory is that biochemical changes within the tendon cause pain. For example, researchers have found significantly higher levels of glutamate, a pain mediator, in tendons with tendinosis compared with normal tendons . Another possible cause of the pain is the neovascularization and accompanying neural network seen in tendinosis.

Diagnosis of tendinopathy

Clinically, tendinopathy presents as pain at characteristic sites within the tendon. It is generally made worse with activity and is better with rest, although it can become constantly painful as it progresses. A history of recent change in activity, such as increased sports training, is often found. Physical examination generally reveals pain over the tendon with palpation, pain with passive stretch of the tendon, and pain with resisted action of the tendon. A biomechanical evaluation often reveals structural issues that place the tendon at risk, such as muscle imbalances, poor flexibility around the injured tendon, and less-than-ideal alignment.

Most often, tendinopathy can be diagnosed clinically and imaging is not necessary. To confirm a diagnosis, MRI and ultrasound can show tendinosis and tendon tears. Several studies have examined the sensitivity and specificity of these tests using either clinical symptoms as the gold standard or cadavers in which tendon damage was inflicted. MRI is approximately 77% to 95% sensitive and ultrasound sensitivity has been reported to range from 57% to 100%. Specificity of both procedures has also been reported in a wide range (50%–100%). Because structural changes can be seen in asymptomatic tendons, clinical correlation is essential . Ultrasound has poorer interrater reliability than MRI because even slight alterations in the probe or patient position can change the appearance of the tendon.

Treatment of tendinopathy

Treatment of tendinopathies is varied. Regarding pain relief, nonsteroidal anti-inflammatory drugs (NSAIDs) are often used clinically. Several studies have shown them to be beneficial for acute symptoms, but they are less helpful for chronic tendinopathy . Regarding the effect of NSAIDs on tendon structure, several studies have shown that they may have a favorable effect on tendon healing, whereas others show that they may be detrimental to healing . Other modalities are also often used. Ice and heat most likely help relieve pain just as in other painful musculoskeletal conditions. Ice is particularly therapeutic for acute tendon pain . Clinical trials have not yet proven if ultrasound and electrical stimulation are helpful for either tendon healing or pain relief, although they are frequently used clinically .

The mainstay of treatment in tendinopathy is the correction of training errors and implementation of an appropriate exercise program. In the acute phases, relative rest is encouraged and alternative training to maintain fitness is encouraged (eg, deep-water running for runners who have a lower-extremity tendon problem). Biomechanical and muscle imbalances are addressed, such as poor scapular upward rotation in swimmers who have overdominant latissimus dorsi and rotator cuff tendinopathy or overpronation in runners who have posterior tibialis tendinopathy. Flexibility problems are corrected, such as with limited dorsiflexion in those who have Achilles tendinopathy. As symptoms improve, strengthening is added in the subacute phases of rehabilitation. Once this phase can be accomplished with few symptoms, dynamic exercises that load the tendon and challenge balance and proprioception are added, such as plyometrics to train the tendon and promote proper landing technique in volleyball players who have patellar tendinopathy. Gradual return to sports and sport-specific drills are added as tolerated. For chronic tendinopathy that has failed to improve with these treatments, painful eccentric strengthening has been shown to be effective. The most beneficial programs use twice-daily heavy-load eccentric muscle training 7 days per week for 12 weeks. These programs have been shown to both decrease symptoms and cause tendon healing, as demonstrated through normalization of tendon structure on ultrasound and MRI .

Injections are also often used to treat tendinopathies. Steroid injections have been used for many years to treat these conditions. The efficacy of steroid injections for tendinopathy has been best studied in the shoulder. Subacromial injections have been shown to have a small benefit over placebo in reducing pain at 4 weeks .

Clinically, steroid injections into the tendon sheath at various other sites are often performed, although studies have not yet proven their efficacy. For example, one study comparing peritendinous sheath injections for Achilles tendinopathy found no difference between corticosteroid injections and bupivacaine injections at 6 weeks . Intratendinous injections have traditionally been avoided, because animal studies have shown that these can weaken the tendon. However, recent studies have shown that injections near the tendon (in one study into the retrocalcaneal bursa) also weakened the tendons, and bilateral injections caused even more weakening, most likely from systemic absorption of the steroid . Prolotherapy is another injection used for tendinopathies. Some small preliminarily studies have shown promising results with injections of polidocanol, a sclerosing agent, into areas of diseased tendon that show neovascularization on color Doppler ultrasound, although this has not been widely practiced clinically .

Some clinical trials have reported extracorporeal shockwave therapy to be effective, particularly for calcific tendinosis of the rotator cuff .

Surgery may be considered for tendinopathy that has not improved with conservative care. Currently, adequately randomized control trials measuring the efficacy of surgery are scarce. Surgery has mixed results, with most patients experiencing some pain relief and increase in function . For certain tendinopathies, such as rotator cuff, a high percentage of patients experience recurrent tears within 2 years of surgery .

Acute muscle strain

Acute muscle strain is a common sports injury. Clinically, it presents as sudden onset of localized pain during a strenuous action. Two mechanisms of injury seem to contribute to muscle strains: overuse of a muscle at the end of its range (as can be seen in dancers or martial artists) or an incoordination of muscle action leading to muscle injury (as can be seen in sprinter hamstring strain). The injury usually occurs when a rapid change from eccentric to concentric contraction occurs during the late swing phase. On physical examination, tenderness over the strained muscle and often pain-inhibited weakness of the involved muscle are experienced. If the muscle is torn, bruising may be present over the affected area. Acute muscle strains are classified into three grades: mild (some pain, no loss of strength), moderate (pain, clear loss of strength), and severe (large tear, clear loss of muscle function). Treatment in the acute stage consists of rest and ice. In the subacute stage, which usually begins 3 days after the injury for mild and moderate injuries, gentle concentric strengthening at submaximal levels is begun. By the end of the first week, gentle stretching is added and, as symptoms improve, the eccentric component of strengthening is added. Sport-specific training is added as symptoms allow.

Although each episode has a good prognosis, a high rate of reinjury exists. For example, the rate of recurrent hamstring strain is 12% to 31%. Risk factors for the development of muscle strains include fatigue (most likely to occur near the end of a sporting match), insufficient warm-up, history of previous injury, and, in the case of hamstring strains, hamstring tightness and low hamstring-to-quadriceps strength ratio . Most of these risk factors can be improved with appropriate training, and evidence shows that muscle strains can be prevented. For example, Hartig and Henderson studied military recruits divided into two groups. One group performed the usual fitness program and the other group added three hamstring stretching sessions a day. The group that stretched experienced 16% hamstring strains and the group that did not experienced 29%. In another preventative approach, Askling and colleagues added a specific hamstring concentric and eccentric strengthening program to the regular preseason training in a group of elite soccer players and compared them with the regular training group. Results showed that the hamstring strengthening group experienced significantly fewer hamstring strains and had faster running times. These studies may have wider implications for muscle strains associated with work-related injury or other sports.

Chronic muscle pain

In contrast to acute muscle strains, the cause of chronic muscle pain is often unclear and the pain is resistant to treatment. Although the term muscle pain is a broad descriptor, the term myofascial pain describes a much more specific regional problem characterized by the presence of myofascial trigger points. Because of space limitations, this article focuses only on the broader term of muscle pain. However, many concepts on the origin and treatment of chronic muscle pain also apply to myofascial pain.

To better understand and treat muscle pain, experimental models have been developed. Usually, a substance such as hypertonic saline is injected into the muscle to cause pain and its effects are studied. Researchers have found that subjects usually report pain at the site of injection and distal to the injection in a predictable pattern of referred pain that varies with the muscle studied. Subjects also develop hyperalgesia in the affected areas. Individuals already experiencing pain in the area have additional findings. For example, when the tibialis anterior is injected in patients who have knee OA, the muscle pain is more severe, the area of referred pain is larger, and symptoms are also seen on the contralateral side . These findings can be explained by theories of how the nervous system processes pain. It also explains many of the phenomena seen clinically, such as the difficulty in localizing muscle pain because of the inability to distinguish primary from referred pain and the hyperalgesia to palpation. In addition to pain that begins in muscles, other structures can refer pain to muscles and cause identical symptoms to those caused by muscle irritation (eg, cervical zygapophyseal joints can cause referred pain into the trapezius muscle, whereas visceral structures such as the gall bladder may cause referred pain to the shoulder mimicking that of muscular pain, and nerve injuries can cause pain and even trigger points in the muscles they innervate) .

All of these factors make diagnosing chronic muscle pain difficult. Treatment should target these underlying causes, but treating the muscular component of the pain with evidence-based techniques that have been known to reduce muscle-based pain is also appropriate.

First-line treatment for chronic muscle pain is exercise. Similar to the treatment of OA, it is generally a combination of aerobic conditioning to increase overall fitness, and focal strengthening and stretching exercises to correct biomechanical deficits so that the central and peripheral mechanisms that may influence the pain can be addressed. Medications are also often used for muscle-based pain. NSAIDs are often used for their analgesic effect, because inflammation is not considered to play a major role in muscle-based pain. Tricyclic antidepressants have been found to be efficacious for treating many chronic pain conditions, including muscle-based pain. These agents are usually used at doses well below those required to treat depression. Selective serotonin reuptake inhibitor antidepressants have not been shown to be helpful in treating pain, but some of the dual reuptake inhibitors, such as duloxetine and venlafaxine, have been shown to be helpful in treating fibromyalgia, a disease that manifests as muscle pain . Injections and dry needling are also common treatments for muscle pain. Dry needling and local anesthetic injections into trigger points have been found to be efficacious for treating myofascial pain. Some practitioners inject botulinum toxin into trigger points, and small case series have described this procedure as therapeutic . Acupuncture is also commonly used to treat muscle-based pain .