Platelet Rich Plasma Prolotherapy as First-line Treatment for Meniscal Pathology

Platelet Rich Plasma Prolotherapy as First-line Treatment for Meniscal Pathology

Ross Hauser, MD  Phillips H, Maddela H. Platelet Rich Plasma Prolotherapy as first-line treatment for meniscal pathology. Practical Pain Management. 2010;July/August:53-64.

Meniscus injuries are a common cause of knee pain, accounting for one sixth of knee surgeries. Tears are the most common form of meniscal injuries, and have poor healing ability primarily because less than 25% of the menisci receive a direct blood supply.

While surgical treatments have ranged from total to partial meniscectomy, meniscal repair and even meniscus transplantation, all have a high long-term failure rate with the recurrence of symptoms including pain, instability, locking, and re-injury.

The most serious of the long-term consequences is an acceleration of joint degeneration. This poor healing potential of meniscus tears and degeneration has led to the investigation of methods to stimulate biological meniscal repair.

Research has shown that damaged menisci lack the growth factors to heal. In vitro studies have found that growth factors, including platelet derived growth factor (PDGF), transforming growth factor (TGF), and others, augment menisci cell proliferation and collagen growth manifold. Animal studies with these same growth factors have confirmed that meniscal tears and degeneration can be stimulated to repair with various growth factors or solutions that stimulate growth factor production. The injection technique whereby the proliferation of cells is stimulated via growth factor production is called Prolotherapy. Prolotherapy solutions can include dextrose, human growth hormone, platelet rich plasma, and others, all of which stimulate connective tissue cells to proliferate.

A retrospective study was done involving 24 patients, representing 28 knees, whose primary knee complaints were due to meniscal pathology documented by MRI. The average number of Prolotherapy visits was six and the patients were followed on average 18 months after their last Prolotherapy visit.

• Prolotherapy caused a statistically significant decline in the patients’ knee pain and stiffness. Starting and ending knee pain declined from 7.2 to 1.6, while stiffness went from 6.0 to 1.8.
  • Prolotherapy caused large improvements in other clinically relevant areas such as range of motion, crepitation, exercise, and walking ability.
  • Patients stated that the response to Prolotherapy met their expectations in 27 out of the 28 knees (96%).
  • Only one out of the 28 patients ended up getting surgery after Prolotherapy.
• Based on the results of this study, Prolotherapy appears to be an effective treatment for meniscal pathology. While this is only a pilot study, the results are so overwhelmingly positive that it warrants using Prolotherapy as first-line therapy for meniscal pathology including meniscal tears and degeneration.

EPIDEMIOLOGY OF MENISCAL INJURIES

Knee injuries are a common concern resulting in over 1 million surgeries performed to the knee in the United States every year.1-3 According to the National Athletic Trainers’ Association, knee injuries account for 10% to 19% of high school sports injuries and 60.3% of all high school athletic-related surgeries.4 Similar studies of collegiate sports have shown that knee injuries make up 7% to 54% of athletic injuries, varying by the nature of the sport.5-9 The leading injuries to the knee, in both adults and children alike, are primarily patellofemoral derangements or ligament strains and tears.10-12 Secondary to these injuries are meniscal tears, which have generated particular interest in both the young and elderly population as studies over the past several decades have revealed a rise in both degenerative and traumatic meniscal injuries. Meniscal tears occur as early as childhood, where they serve as the leading cause of pediatric arthroscopy, and increase with age and activity.13, 14 An estimated one sixth of knee surgeries are performed for lesions of the meniscus, and it is likely that many more remain untreated every year.15, 16 In one study of cadaver knees, untreated meniscal lesions were found in 34% of the autopsied subjects.17

A significant percentage of meniscal injuries result from athletic injury. On a professional level, meniscal tears accounted for 0.7% of all injuries sustained in the National Basketball Association, totaling 3,819 days missed by NBA athletes over a 10 year span.18 In college sports, studies conducted over a 16 year span by the National Collegiate Athletic Association Injury Surveillance System found internal knee derangement was second only to ankle sprains in both men’s and women’s college basketball and men’s and women’s soccer.5-8 An independent study of college football had equally devastating statistics, reporting injuries to the meniscus in roughly one in five elite college football athletes.9 With participation in college sports on the rise, the number of meniscal injuries and subsequent surgeries are consequently rising at an alarming rate.19 Although athletes appear to have the highest instance of injury, meniscus injuries can happen anywhere, regardless of a person’s level of activity. A research study conducted in Greece showed that meniscal tears developed equally from traumatic and non-traumatic causes with 72% of all meniscal tears occurring during normal activities of daily living.20

MENISCUS ANATOMY & FUNCTION

The menisci (plural of meniscus) are a pair of C-shaped fibrocartilages which lie between the femur and tibia in each knee, extending peripherally along each medial and lateral aspect of the knee. (See Figure 1.) The anatomy of both menisci is essentially the same, with the only exception being that the medial meniscus is slightly more circular than its hemispherical lateral counterpart. Each meniscus has a flat underside to match the smooth top of the tibial surface, and a concave superior shape to provide congruency with the convex femoral condyle. Anterior and posterior horns from each meniscus then attach to the tibia to hold them in place. The meniscus is comprised of approximately 70% water and 30% organic matter. This organic matter is primarily a fibrous collagen matrix consisting of type I collagen, fibrochondrocytes, proteoglycans, and a small amount of dry noncollagenous matter.21, 27 There has been a great deal of speculation and research dedicated to what exact function the meniscus serves, but today there is general consensus that the menisci provide stability in the joint, nutrition and lubrication to articular cartilage, and shock absorption during movement.21-25

The menisci provide stability to the knee joint by both restricting motion and providing a contour surface for tibiofemoral bone tracking. The function of providing knee stability is shared with several ligaments which work together to prevent overextension of any motion. The transverse ligament connects the two menisci in the front of each knee and prevents them from being pushed outside of the joint at any point. Hypermobility is avoided through the connection of the medial collateral ligament (MCL) to the medial tibial condyle, femoral condyle, and medial meniscus, and the connection of the lateral collateral ligament (LCL) to the lateral femoral epicondyle and the head of the fibula; these ligaments provide tension and limit motion during full flexion and extension, respectively. The anterior and posterior meniscofemoral ligaments form an attachment between the lateral meniscus and the femur and remain taut during complete flexion. Lastly, the anterior cruciate ligament (ACL) and posterior cruciate ligament (PCL) are responsible for preventing too much backward or forward motion of the tibia.23, 24

The menisci also provide shock absorption and stability by equally distributing weight across the joint. It is estimated that 45% to 70% of the weight-bearing load is transmitted through the menisci in a completely intact joint.21 By channeling the majority of this weight evenly, the meniscus is able to avoid placing too much direct stress at any one point of the knee. In turn, proper weight transmission in the knee reduces stress on any other joints in the body affected by load bearing.25

One of the most vital roles of the meniscus is to provide lubrication to the knee, which it accomplishes through diffusing synovial fluid across the joint. Synovial fluid provides nutrition and acts as a protective measure for articular cartilages in the knee.26 The femoral condyle in the knee is covered in a thin layer of articular cartilage, which serves to reduce rotational friction and to withstand weight bearing. This cartilage is very susceptible to injury both because of its lack of proximity to blood supply and the high level of stress placed on it by excessive motion.27, 28 The meniscus, therefore, is able to provide a much-needed source of nutrition to the femoral and tibial articular cartilage by spreading fluid to that avascular area.

By acting as a spacer between the femur and tibia, the meniscus eliminates any direct contact between the bones, preventing any contact wear.29 To see what effect the presence of the meniscus has on degeneration within the knee, researchers from the UK at the Institute of Medical and Biological Engineering conducted an in vitro study by mounting dissected bovine knee joints in a pendulum friction simulator and monitoring wear on knee cartilage both with and without a meniscus. Their results showed no change in surface integrity or loss of cartilage with an intact meniscus, but removal of the meniscus resulted in immediate surface wear and cartilage deterioration.30

The ability to preserve the meniscus, unfortunately, is somewhat hampered by the fact that only a very small percentage (10% to 25% peripherally) of the meniscus receives direct blood supply.31 This area is often referred to as the red zone, and the inner portion of the meniscus which does not receive blood supply is referred to as the white zone. While the red zone has a moderate chance of healing from injury, the white zone is almost completely incapable of healing itself in the event of injury.32

INJURY
Tears are the most common form of meniscal injury, and are generally classified by appearance into four categories: longitudal tears (also referred to as bucket handle tears), radial tears, horizontal tears, and oblique tears.33 (See Figure 3.) Research indicates that radial or horizontal tears are more likely to occur in the elderly population while younger patients have a higher incidence of longitudal tears.34-36 Each can be further described as partial thickness tears or complete thickness tears, depending on the vertical depth of the tear. (See Figure 4.)

Meniscal damage can be caused by either trauma or gradual degeneration. Traumatic injury is most often a result of a twisting motion in the knee or the motion of rising from a squatting position, both of which place particular strain and pressure on the meniscus. More often than not, traumatic injuries occur during athletic activity. The ratio of degenerative to traumatic tears increases from equal incidence in those under 20 years of age to a ratio of 7:8 in the 30 to 39 age group, to nearly 4:1 in individuals over the age of 40.20 This pattern of increased degenerative breakdown is to be expected with age, as joint wear will result from years of mechanical stress. Unlike the anatomy of younger and more active patients, however, the fibers in older patients are less capable of healing themselves, due to decreased diffusion of synovial fluid with lessened motion.37

A basic ability to identify meniscal tear symptoms is essential for diagnosis and treatment of injury. (See Figure 5.) The first symptom typically indicative of a meniscal tear is pain. In the case of a traumatic tear, pain may present immediately at the time of injury and is often accompanied by an audible pop. In a degenerative tear, the onset of pain may be more gradual, with no definite moment of injury. In both cases, pain may be accompanied by swelling and subsequent limitation in range of motion. Another hallmark of meniscal tears is clicking, popping, or locking in the knee joint. These symptoms are most likely a result of a torn flap of meniscal tissue which catches in the joint during movement. Instability and weakness are also both common symptoms because a damaged meniscus, as well as damaged ligaments and tendons, inhibits normal mechanical function.

The severity of initiating trauma, as well as the nature and characteristics of the tear, plays an important role in the meniscus’ ability to heal. (See Figure 6.) Tears that are shorter, partial thickness, and located in the vascular red zone have a much better chance of healing than extensive, complete thickness tears located in the white zone.38, 39 When other cartilages and ligaments are injured in the knee, this can also have a detrimental effect on the meniscus’ ability to heal on its own. Because of the interdependence of each of the knee’s mechanisms, meniscal injuries often occur in conjunction with other internal ligament damage; the most common example of this is O’Donoghue’s “unhappy triad,” the correlated injury of the meniscus (debatably either medial or lateral), tibial collateral ligament, and ACL.40-42 The severity of meniscal lesions has been found to increase in direct proportion to ACL injury and/or laxity, and create less favorable conditions for repair.43 Furthermore, previous injury to either the meniscus or any other ligament inside the knee can increase the risk of future injury to the meniscus, even if the injury has healed or been surgically repaired.

Another condition which can be both a cause and complication of meniscal tears is a discoid meniscus. (See Figure 7.) A discoid meniscus occurs when the lateral meniscus takes on the shape of a disc, rather than a crescent, and is most often manifested in adolescence.44 Although the cause has never been officially determined, the repercussions of a discoid meniscus have been widely documented. Often referred to as “snapping knee syndrome,” this condition is identified with its only symptom, snapping on extension. The “snap” is caused when the femur and the meniscus are not able to move in sync with each other and the femur either slips over a ridge in the meniscus or off of the meniscus altogether.45 Unlike the normal meniscus, which is shaped to fit the condyle of the femur, a discoid meniscus lacks the configuration to serve as a stable surface for motion. This abnormal tracking adds stress on the meniscus, increasing the probability of lateral meniscus tears.46 Unfortunately, discoid menisci often remain undetected when no symptoms present prior to injury, and the only other way to identify a discoid meniscus is by magnetic resonance imaging (MRI).

 IMAGING

For decades, MR imaging has been used as a primary determinant for meniscal injuries. MR imaging uses magnetic frequency to read radio waves given off by protons in the body; through these waves, the MRI is able to identify different tissues in the body and produce a semi-accurate picture of these tissues. The fact that MR imaging is more sensitive to some tissues than others, however, can prevent it from producing a completely accurate picture of an injured area. This can cause injured tissues to remain undetected, or other “abnormalities” on the MRI to be misread as actual injuries. These errors include shadows, truncation artifacts, and even foreign tissues, such as scar tissue, that can have the appearance of an injury on an MRI film. As a result, relying on MR imaging alone, especially as it relates to meniscal tears, will very often lead to an improper diagnosis and, subsequently, improper treatment.

One study that brought these issues into the spotlight was performed on college basketball players at Duke University who displayed no clinical symptoms of knee abnormality. Internal irregularities of the knee including cartilage defects, joint effusions, bone marrow edema, and even discoid menisci were found on the MRIs of 75% of subjects, who never displayed any symptoms of meniscal abnormality.47 When an MRI shows a tear or meniscal degeneration when the person has no symptoms, this is called a false positive. The MRI is falsely positive. Kornick and associates investigated 64 volunteers, between the ages of 10 and 74, and found that over 25% had abnormal signals in their menisci, despite being totally asymptomatic.48 More distressing is the fact that in another study on children, mean age 12.2 years, 66% showed a high signal intensity within the menisci.49 A high signal intensity is one of the criterion to diagnose degenerative menisci. (See Figure 8.) Perhaps the best study to date to document abnormal meniscal MRI findings in asymptomatic individuals was published in the New England Journal of Medicine in 2008.50 In this study, MRI scans on 991 knees were taken and compared to clients responses about pain and disability in those knees. The prevalence of meniscal tear or of meniscal destruction in the knee as detected on MRI ranged from 19% among women 50 to 59 years of age to 56% among men 70 to 90 years of age. The MRIs in these patients ages 50 to 90 showed that over 60% had meniscal tears documented on MRI and that 61% of subjects who had meniscal tears did not have any pain, aching, or stiffness in their knees.

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• Surgery
• NSAIDs
• Cortisone Shots
• R.I.C.E.