27 Nov Platelet Rich Plasma Prolotherapy as First-line Treatment for Meniscal Pathology
Animal research together with five patient case reports demonstrate that platelet rich plasma prolotherapy (PRPP) is effective in the treatment of MRI-documented meniscal tears.
Knee injuries are a common concern resulting in over one million surgeries performed on the knee in the United States every year, including the meniscus.1-3There are an estimated 650,000 arthroscopic meniscal procedures, with a total number of 850,000 meniscal surgeries performed in the United States every year.1-3 Unfortunately, joint instability is a common result of meniscal procedures, which is not surprising considering that the meniscus is a primary stabilizing component of the knee. One of the principle reasons for meniscal operations is to improve joint stability, yet meniscectomy often appears to have the opposite effect, eliciting even more instability, crepitation, and degeneration than the injury itself produced prior to operation. This is why reoperation rates after meniscectomy can be as high as 29% to improve the joint instability that the meniscectomy caused.4-6 For this reason, it is desirable to look for non-operative interventions whenever possible. Platelet rich plasma prolotherapy offers hope in this direction.
Meniscus Anatomy and Function
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.7-11 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.
Several ligaments work together with the menisci to prevent overextension of any motion. Hypermobility is avoided through ligamentous connectionsâ€”both medially and laterally. Medially, the medial collateral ligament (MCL) is strongly connected to the medial meniscus, as well as the medial tibial condyle and femoral condyle. Laterally, the lateral collateral ligament (LCL) attaches 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.9,10
The menisci also provide shock absorption and stability by equally distributing weight across the joint. By acting as a spacer between the femur and tibia, the meniscus eliminates any direct contact between the bones thus preventing any contact wear.12 It is estimated that 45% to 70% of the weight-bearing load is transmitted through the menisci in a completely intact joint.7 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.11
Lubrication and Nutrition
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.13 The femoral condyle in the knee is covered in a thin layer of articular cartilage, which serves to reduce motional friction and to withstand weight bearing. This cartilage is very susceptible to injuryâ€”both because of its lack of proximity to blood supply and the high level of stress placed on it by excessive motion.14,15 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.
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. 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 tears16 (see Figure 2). 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.17-19 Each can be further described as partial thickness tears or complete thickness tears, depending on the vertical depth of the tear (see Figure 3).
Limited Blood Supply
An 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.20 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 (see Figure 4). 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.21
More often than not, traumatic injuries occur during athletic activity (see Figure 5). 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 and to nearly 4:1 in individuals over the age of 40.22 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 as a result of lessened motion.23
Figure 5.A hit on the knee causing a medial collateral ligament injury. If the hit is severe enough, the supporting ligaments of the knee could also be torn. (Used with permission from Hauser, R. Prolo Your Sports Injuries Away, Beulah Land Press, Oak Park, Ill. 2001).
Platelet Rich Plasma for Meniscal Pathology
In order to understand how growth factors affect the treatment of meniscus injuries, it is first important to understand the role that they play in the natural process of healing. The preliminary steps of healing begin with the attraction of blood cells to the site of an injured tissue. When a tissue is injured, bleeding will naturally occur in that area. A specialized blood component called platelets rapidly migrate into the area to initiate coagulation, or the clotting of blood cells, to prevent excessive bleeding from an injury. In addition, platelets also release growth factors which are an integral part of the healing process. Each platelet is made up of an alpha granule and a dense granule which contain a number of proteins and growth factors. The growth factors contained in the alpha-granule are an especially important component to healing. When activated by an injury, the platelets will change shape and develop branches to spread over injured tissue to help stop the bleeding in a process called aggregation, followed by the release of growth factors, primarily from the alpha granules.
At this point, the healing process then proceeds in three basic stages: inflammatory, fibroblastic, and maturation. After growth factors are released from the platelets, they stimulate the inflammatory stage with each growth factor playing a key role (see Table 4). This stage is marked by the appearance of monocytes which are white blood cells that respond quickly to inflammatory signals and elicit an immune response. Growth factor production is at its highest level immediately following the inflammatory stage. Fibroblasts begin to enter the site within the first 48 hours after an injury and become the most abundant cells in that area by the seventh day. The fibroblasts deposit collagen, the main building block of tissues such as the meniscus, for up to many weeks afterward. The maturation of collagen may then continue for up to one to two years after the initial inflammatory event.
It is important to understand that each of these stages stimulates the next. If the inflammatory stage does not occur, neither will the fibroblastic stage, and so on. If there is not a significant enough immune response to completely regenerate the damaged tissue in any of these stages, the injury will be unable to heal completely, leaving the person with a chronic degenerated knee.
Meniscus injuries are a common cause of knee pain. Tears are the most common form of meniscal injuries, and have a 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, one of the most serious long-term sequelae of surgeries for meniscus tears is an acceleration of joint degeneration. This poor healing potential of meniscal tears 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 can be stimulated to repair with various growth factors or solutions that stimulate growth factor production. Platelet rich plasma prolotherapy has been shown to be effective in these five cases of MRI-documented meniscal tears in returning these patients to activity and athletic sports. While more controlled studies need to be completed, the clinical evidence shows that PRPP is a reasonable approach to meniscal injury and should be considered as first-line treatment for meniscal injuries.