Clinical and Health Affairs
Therapeutic Musculoskeletal Injection: What Is Current Practice? What Is the Evidence?
By Jamie Peters, M.D.
Abstract
Physicians are encountering an increasing number of patients with musculo-skeletal injuries and conditions. Although conservative approaches such as rest, ice, elevation, analgesic medications, and therapeutic exercise are usually the first line of treatment, they do not provide relief for some patients. For those patients, injectable agents may be useful in relieving pain and promoting healing. This article describes older and newer injectable agents and reviews the evidence regarding their use and effectiveness.
The number of patients seeking care for musculoskeletal conditions is rising dramatically. There are several explanations for this phenomenon. Many more individuals now understand the health benefits of exercise and suffer injuries as they ramp up their routines. In addition, the obesity epidemic has led to a greater number of individuals predisposed to increased wear and tear on tendons and joints. Another factor contributing to the rise is that fact that the baby boomers are aging. Currently, osteoarthritis affects approximately 15% of the population, 50% of those 65 years of age and older, and 85% of those 75 years of age and older.1 The number of aging baby boomers in the United States is expected to double the prevalence rate of osteoarthritis in the United States by 2020.1
Rest, ice, analgesic medications, and therapeutic exercise (physical therapy) are appropriate first-line treatments for musculoskeletal problems. When these treatments are ineffective, injectable agents may be used to facilitate healing or reduce pain. New injectable products and strategies for using them have been developed for a variety of conditions during the past five to 10 years. This article discusses older and newer injectable products, and the evidence regarding their use for treating specific musculoskeletal conditions.
Corticosteroid Injections
For many years, a number of similar corticosteroid injection products have been available for use in combination with a local anesthetic agent to treat joint and soft-tissue conditions. No one type of corticosteroid product has been shown to be superior to others, and clinicians have tended to choose less-expensive generic products such as triamcinalone over more expensive name-brand ones. As would be expected, the mechanism of action of these products is as a potent anti-inflammatory.
Corticosteroid injection is indicated for conditions associated with inflammation such as bursitis (eg, greater trochanteric bursitis, subaccromial bursitis) and tenosynovitis (eg, Dequervain’s syndrome of the extensor policis longus). Administration involves injecting a bolus of the steroid/anesthetic mixture into the inflamed area such as the bursa or peritendinous sheath. Following the injection, proper rehabilitation includes strengthening and cross-training exercises and avoidance of overuse. This increases the potential for a longer-lasting positive result.
Although osteoarthritis is associated with variable amounts of inflammation, and the actual cause of the associated joint pain is not well-understood, intra-articular bolus injection of corticosteroid/anesthetic for patients with osteoarthritis in weight- and nonweight-bearing joints often reduces their pain for up to three months. With their pain under control for a period of time, patients have the opportunity to correct the destructive muscle imbalances that are usually present with osteoarthritis.2 Unfortunately, as their condition progresses, the duration of pain control from subsequent injections diminishes.
The risks associated with corticosteroid injections, about which patients need to be informed, include skin depigmentation, fat necrosis, tendon rupture, and infection. Systemic absorption of the corticosteroid is minimal, but not insignificant. One longer-acting local anesthetic agent, bupivacaine (Marcaine), which has commonly been used for intra-articular injections of corticosteroids, has been associated with toxicity. In 2008, Piper, et al. published a study in the Journal of Bone and Joint Surgery comparing bupivacaine’s toxicity with that of another anesthetic agent, ropivacaine. Bupivacaine was found to be significantly more toxic in vitro to articular cartilage.3 Consequently, many clinicians familiar with this study have reduced or eliminated their use of bupivacaine when giving intra-articular injections.
The long-term results of corticosteroid injections for the treatment of soft-tissue tendon conditions such as lateral epicondylitis (tennis elbow) has been disappointing. These conditions, which are often associated with overuse, are frequently located at the enthesis, the juncture where the tendon attaches to the bone. Histologically, these types of conditions demonstrate tissue degeneration with tendon- related neovascularization and disorganized collagen formation rather than inflammation. Microneovascularity (new vessels) is thought to be the source of pain. Appreciation of this histologic observation has led to a change in terminology from “tendonitis” to “tendinopathy” along with a change of specific entity descriptors (ie, “lateral epicondylosis” rather than “lateral epicondylitis”). The lack of inflammation as a component of these conditions explains the limited success with corticosteroid injections and oral NSAIDs and has led to a search for other agents that could more effectively treat these conditions.4 More recent physiotherapy strategies that use eccentric strengthening (resistance training with the muscle lengthening rather than shortening) have been promising as an alternative treatment strategy.5
Viscosupplementation
An effective alternative to corticosteroid injections for the treatment of osteoarthritis is intra-articular injection of hyaluronic acid. Currently, five FDA-approved hyaluronic acid products are available for viscosupplementation. Three of the products (Synvisc, Hyalgan, Orthovisc) are derived from rooster combs. The other two (Supartz and Euflexxa) are engineered from fermented bacterial sources. Although these products have molecular differences and are administered differently, none of the evidence favors one over another.6 A course of treatment of viscosupplementation ranges from a single intra-articular injection (Synvisc-One) to one injection weekly for five consecutive weeks (Supartz).
Hyaluronic acid is found naturally in the joint and is synthesized by chondrocytes in the cartilage. It is a key component of synovial fluid. As osteoarthritis progresses, the amount of synovial fluid decreases, as does its viscosity. The proposed mechanism of these products is that they increase the viscosity and lessen the degradation of the synovial fluid, thereby improving its volume and quality over an extended period of time. This is likely responsible for the long duration of pain reduction post injection.
Data from a number of studies comparing corticosteroid and hyaluronic acid injections for osteoarthritis have shown that the duration of effective pain relief with corticosteroid injection is 14 weeks or less, whereas the duration of pain relief with hyaluronic acid injection often exceeds 14 weeks.7 Other recent studies have shown that clinicians have used hyaluronic acid products successfully in the ankle, hip, hand, and shoulder joints as well as the knee.8 All of the hyaluronic agents are expensive (in the range of $1,500 per course), which is a major reason why most clinicians initially use corticosteroid products to treat patients with osteoarthritis. Only a few studies have compared various hyaluronic acid products, so there currently is no compelling evidence guiding the use of one over another.
Platelet Rich Plasma/Autologous Blood Injections
A newer approach to treating degenerative soft-tissue overuse conditions such as lateral epicondylosis, plantar faciitis, and patellar and achilles tendinopathies—conditions that often do not respond to conservative treatments or corticosteroid/lidocaine injections—involves the use of platelet-rich plasma (PRP) and autologous blood (AB) injections. The proposed mechanism of action of PRP and AB is based on the potential benefit of growth factors, cytokines, and other bioactive substances that are present in high concentration in platelets. These positively affect the healing of degenerated tissue. A number of studies investigating the use of PRP and AB have received attention in the popular press. However, there is still a lack of high-quality, prospective research to definitively assist physicians in the appropriate use of these agents.9 That being said, early use of these agents for conditions that are often resistant to other treatments has been encouraging.10 In addition, PRP and AB have less potential for serious side effects such as tendon rupture and fat necrosis than corticosteroids.
Autologous blood treatment protocols involve injecting a local anesthetic in the affected region and then performing venipuncture and reinjecting the patient’s blood in the abnormal tissue. PRP involves taking blood from the patient, spinning it in a centrifuge to separate blood cells, and returning it with a higher concentration of platelets to the injured site. Several commercially available centrifuge devices are available for use in physicians’ offices. These devices achieve varying concentrations, with whole blood-to-platelet ratios ranging from 1:2 to 1:8. The ratio of WBC content also varies with the device. Obviously, the ratio of plasma to platelets in autologous blood is 1:1. The ideal ratio of plasma to platelets and the ideal amount of WBC concentrate is not well-established at this time because of the lack of high-quality studies.
Recently, several high-profile athletes have claimed PRP injections shortened the healing time for large muscle/tendon (hamstring/quadriceps) injuries. Supported by some encouraging animal studies, the proposed mechanism of PRP is enhanced myogenesis with delivery of growth factors to the site of injury, thereby accelerating muscle healing while decreasing potential scar formation.11 Clearly, further high-level research is needed to determine the appropriate use of these treatment strategies.
A recently published randomized, double-blind study by De Vos et al. using PRP for the treatment of Achilles tendinopathy did not demonstrate significant improvement compared with placebo injection.12 However, the patients studied were selected prior to having any other conservative treatment such as eccentric strengthening. In a recent commentary about this study, the authors speculated that selecting the patients from a group that had failed conservative treatment (the more typical clinical scenario) may have produced more favorable results.13
Platelet-rich plasma injections have shown promising early results when used intraoperatively in a number of orthopedic surgeries. Specifically, PRP has been used as an adjuvant for surgical repair of rotator cuff and Achilles tendon tears. Positive outcomes were demonstrated when used in ACL repairs on animal models, although a human study thus far has not demonstrated improved results.9 Despite the early optimism about and positive safety profile of PRP and AB, most insurance companies are reluctant to cover the use of these agents because of the lack of high-quality randomized, double-blinded studies.
Sclerotherapy and Prolotherapy
Polidocanol is a sclerosing agent used in the treatment of varicose veins. Recently, it has been studied for the treatment of soft-tissue degenerative-type conditions such as lateral epicondylosis with some success.14 The proposed mechanism of action is to induce a healing reaction within the degenerated tissue following injection, thereby reducing neovascularization, which is thought to be associated with pain.
Prolotherapy is a treatment for soft-tissue conditions that has been used since the 1930s for back pain. The injectant frequently contains a hyperosmolar dextrose solution and morrhuate sodium (also a vascular sclerosant). Like sclerotherapy, prolotherapy has been used to induce healing in degenerative tissue associated with tendinopathies. As with PRP and AB, further randomized, double-blind comparison studies are needed to assist the clinician in the proper selection of these treatment options.4
Needling/Peppering
The technique used by most clinicians to inject corticosteroid for treatment of tendinopathies associated with degenerated tissues is called needling or peppering. It involves a fanning in and out of the needle while injecting the affected tissue. A recent prospective randomized study compared dry needling (the injection technique used without an injectant) with using the same technique and a corticosteroid/lidocaine. The results showed similar outcomes for each group.14 One conclusion that could be drawn from this study is that the trauma from this type of injection causes irritation and the local release of blood, which produced a healing effect much like that produced by autologous blood injections.
Conclusion
When treating a patient with a musculoskeletal injury or condition, it is best to start with noninterventional approaches such as physiotherapy, ice, and analgesics. If conservative treatment fails, injectable agents may help. Corticosteroid injections are effective in reducing pain associated with osteoarthritis and in the treatment of conditions in which inflammation is present. When corticosteroid treatment is not effective for osteoarthritis, intra-articular injections with hyaluronic acid are another option. Hyaluronic acid injections provide longer-lasting pain relief than corticosteroids for patients with osteoarthritis, but they are much more expensive. Platelet-rich plasma and/or autologous blood injections are safer and may be more effective than corticosteroids for treatment of tendinopathies and other musculoskeletal conditions. But physicians need to understand that high-quality prospective evidence as to the appropriate use of some of these treatments for certain conditions is lacking. MM
James Peters is a primary care sport medicine physician with Fairview Sports and Orthopedic Care.
References
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