Efficacy Study of Prolotherapy vs Corticosteroid for Tennis Elbow
Condition: Lateral Epicondylitis
MeSH terms: Tennis Elbow
Study type: Interventional
Phase: Phase 3

Summary: 
      The purpose of the research is to study the effects of two different injection therapies for
      the treatment of lateral epicondylitis (tennis elbow). Specifically, we will look at which
      therapy provides better short and long-term relief of pain, which treatment allows better
      function and less disability, and which treatment gives back better strength in the affected
      hand. Each subject will receive only one of the two treatments. Although both of these
      treatments are usually very well tolerated, it is important to make this comparison because
      it is believed that one of these therapies may have better long term effectiveness, with a
      lower cost, and smaller number of potential side effects.
    

Detailed description: 
      Lateral Epicondylitis or tennis elbow is one of the most commonly diagnosed upper-extremity
      musculoskeletal disorders seen in general practice. It is characterized by painful
      enthesopathy or tendinosis of the common extensor tendon at the outer region of the elbow at
      the fibro-osseous junction. "Although tennis elbow" was originally made note of in the
      medical literature by Runge in 1873, the term derives from "Lawn Tennis Arm" later described
      by Morris in 1882.

      Traditionally, lateral epicondylitis causes characteristic pain in the lateral elbow region
      and is often associated with significant morbidity. It occurs most commonly in individuals
      between 40 and 50 years and equally affects both men and women. The dominant arm is involved
      in 75% of patients. While other etiologies have been proposed, including radial nerve
      entrapment, it is generally agreed that tennis elbow is the result of repetitive mechanical
      micro-trauma and overuse, but many cases have no biomechanical association, nor vocational or
      avocational correlation. This condition is often brought about by repeated flexion and
      extension of the wrist or by a direct injury to the epicondyle or elbow. However, most
      patients are unable to recall or to identify a precipitating event. The average duration of
      an episode of lateral epicondylitis is 6 to 24 months, and 10% to 30% of cases result in work
      absenteeism, leading to a high loss of productivity. Numerous treatment options have been
      described for lateral epicondylitis. Most cases are managed in primary care settings, and
      although there are more than forty possible treatments, there is still a lack of consensus
      about optimal therapeutic management. Moreover, most of these treatments lack sound
      scientific evidence.

      The preferred method of treatment of lateral epicondylitis often involves corticosteroid
      injections with or without the addition of local anesthetic. In general, injection of local
      corticosteroids is commonly used to reduce inflammation in patients with chronic
      tendinopathies such as lateral epicondylitis. However, since inflammation is not necessarily
      a major feature in this lesion, and if present, may present a vital component of the healing
      response. Inhibiting this process may result in a suboptimal outcome. Thereby, despite their
      popularity, the rationale for use of corticosteroids is controversial and the evidence for
      long-term benefit lacks. Likewise, potential side effects such as infection, tissue atrophy,
      pigmentation changes, hyperglycemia, etc. do exist. Moreover, many of the recommendations for
      the use of corticosteroid injections are anecdotal. In a review by Labelle et al, it was
      concluded that there was insufficient scientific evidence to support the use of
      corticosteroids injections for lateral epicondylitis. Assendelft et al came to similar
      conclusions in his review when he found that existing evidence on corticosteroid injections
      for lateral epicondylitis was unclear and that questions regarding the optimal timing,
      dosage, injection, technique, and injection volume remained unanswered.

      Prolotherapy, though not as yet extensively studied, is another emerging therapy presenting
      as an alternative to corticosteroid injection for the treatment of lateral epicondylitis. It
      continues to rise in popularity, especially by clinicians who commonly treat musculoskeletal
      injuries. With its early origins dating back to the time of Hippocrates, prolotherapy is
      defined as the iatrogenic stimulation of wound healing and tissue repair process through the
      injection of an irritant solution into damaged ligaments, tendons, and joints thus
      encouraging their healing and repair.

      Essentially, this occurs as a result of a localized inflammatory reaction with stimulation of
      rounds cell infiltration with resultant collagen synthesis, and formation of firm permanent
      fibrous tissue and bone. The new collagen runs parallel to existing ligaments and tendons and
      has a linear orientation, resulting in ultimate strengthening and stabilization of the
      ligament, tendon, or joint with subsequent reduction of pain. It is generally safe and very
      well tolerated and has been used throughout the western medical community for over 50 years.

      Existing research on prolotherapy began in the 1930s when Lerich first described the rich
      supply of nerve endings in articular ligaments. This was re-introduced by Gardner in 1953.
      Also in the 1950s, Hackett, who described most joint pain as ligamentous, was the first to
      scientifically demonstrate a method of strengthening ligaments by injection of a proliferant
      solution. At that time, the use of an irritant solution was thought to work by creation of a
      scar tissue rather than by development of a proliferative response. As pain was perceived to
      arise when normal tension on a ligament stretched the relaxed ligament fibers, which resulted
      in abnormal tension and stimulation of the sensory nerves because the nerve fibers did not
      stretch, reduction of pain was thereby thought to arise with stabilization of these relaxed
      ligaments through generation of a strong scar tissue about that structure. Reduction of pain
      was realized by Hackett who reported an 82% success rate in the treatment of chronic spinal
      pain in 1816 patients treated during a 20-year period.

      A subsequent study in 1982 on rabbit ligaments by Lui et al showed that prolotherapy might
      have a positive effect on mass, thickness, enthesis strength, and weight-to-length ratio of
      injected ligaments, as compared to controls. A different study by Klein et al in 1989 showed
      histological documentation of ligament proliferation in human subjects. This was in response
      to proliferative injections, which objectively increased the diameter of collagen fibers with
      an associated decrease in pain as well as an objective increase in range of motion. In
      another study, Ongley et al found a statistically significant reduction in ligamentous laxity
      9 months after injecting the ends of collateral and cruciate ligaments of knees that had
      substantial ligamentous laxity as measured by a computerized knee analysis device. All of
      these studies found decreases in pain levels of patients involved.

      In addition to early studies, which focused on the mechano-proliferative effects, later
      studies in proliferant injection therapy considered its affect on both subjective pain levels
      and more objective outcomes such as functional status. For example, in Ongley's study, more
      patients in the experimental group showed improvements in pain with a concomitant decrease in
      levels of disability. Faber et al, using a dextrose, phenol, and glycerin containing
      proliferant, were able to document an increase in the size of sacroiliac ligaments. They also
      were able to show a moderate to marked improvement in pain and function in subjects who
      received prolotherapy in concert with manipulation versus controls who received saline
      injections and sham manipulations. Reeves et al showed that prolotherapy solution consisting
      of 10% dextrose resulted in clinically and statistically significant improvements in patients
      with knee osteoarthritis. The clinically significant changes were seen in joint pain,
      subjective joint swelling, flexion range of motion, and in tendency to buckle, all signs
      which significantly impact level of function.

      Although these and other studies have shown positive effects of proliferant therapy on
      mechanical properties of ligaments as well as subjective improvements in pain and function,
      most have suffered from small sample size, inadequate controls, and inconsistency of study
      design and methodology. Kim et al reviewed and critically analyzed three randomized,
      controlled studies on the use of dextrose, glycerin, and phenol prolotherapy for chronic low
      back pain. They found inconclusive data to support its use due to the lack of adequate
      controls, heterogeneity in patient diagnoses, and variations in solutions injected.
      Nevertheless, clinical use of prolotherapy warrants further investigation.

      As lateral epicondylitis involves a cascade of injury at or about the insertion of the common
      extensor tendon at the fibro-osseous junction, the patho-physiologic response to
      proliferation at this joint seems promising. Based on previous studies, prolotherapy would
      theoretically strengthen and stabilize the overstretched and torn strands of fibrous tissue
      that cause the cascade of instability and generation of pain at this junction. Not only would
      prolotherapy thereby improve subjective pain, it would improve objective strength and
      stability of the joint with resultant increase in function. Moreover, in doing so,
      prolotherapy would benefit both the patient and society at large by offering a relatively
      safer, less expensive, and longer lasting alternative to corticosteroids.
    

Intervention name(s): Prolotherapy; Local Corticosteroid Therapy
Intervention type(s): Drug; Drug
Allocation: Randomized
Intervention model: Single Group Assignment
Masking: Double
Primary purpose: Treatment
Keywords: Prolotherapy; Lateral Epicondylitis; Tennis Elbow; Corticosteroid Therapy