Efficacy Study of Prolotherapy vs Corticosteroid for Tennis Elbow

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 "Although tennis elbow" was originally made note of in the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.