Prolotherapy Treatment for Meniscal Tears

Journal of Prolotherapy. 2010;2(3):416-437.
KEYWORDS: human growth hormone, meniscal degeneration, meniscal tear, meniscus, platelet rich plasma, Prolotherapy. Page 3 Page 2 Page 1

The Case for Utilizing Prolotherapy as First-Line Treatment for Meniscal Pathology: A Retrospective Study Shows Prolotherapy is Effective in the Treatment of MRI-Documented Meniscal Tears and Degeneration
Ross A. Hauser, MD, Hilary J. Phillips, and Havil S. Maddela

The traditional management of a torn meniscus most often involves some measure of surgical treatment, such as partial or total meniscectomy, meniscal repair, or meniscal transplant. There are an estimated 650,000 arthroscopic meniscal procedures and a total number of 850,000 meniscal surgeries performed in the United States every year.^1-3

The most aggressive surgical treatment is meniscectomy, which involves either complete or partial removal of the meniscus depending on the horizontal extent of the tear. Guided by Arthroscopy, the damaged portion of the meniscus is surgically debrided and removed. In either operation, a peripheral rim of the meniscus must be kept to preserve any form of normal function within the knee. The decision of whether to remove all or part of the meniscus is based on the severity of the tear, the restriction of activity caused by the tear, and the age of the tear.

Total meniscectomy is generally performed on the most severe and avascular tears which cannot be otherwise repaired.^62-63 Short-term follow-up of meniscectomy has generated some positive results. For example, a meniscectomy can provide temporary pain relief in early stages following the operation, especially when an acute tear had caused excessive pain or popping preoperatively. Another immediate result may be a greater feeling of stability, if the tear had previously been a source of instability. On long-term follow-up, however, these initial improvements have rarely been shown to last.^63-65

Complete pain relief from meniscectomy is nearly unheard of after more than 10 years and, at that point, more complex issues including limited range of motion, radiographic degeneration, crepitation, and severe functional impairment have usually begun to surface. In many cases, a simple meniscus tear, if operated on, can become a career-ending injury.^63-66 In long-term follow-up studies, four to 14 years after a meniscectomy, nearly 50% of patients had to decrease or stop their typical sporting activities.^63-64 This included the adolescents who underwent total meniscectomy. The X-ray progression of the degenerative change paralleled the reduction in activity. Some 17 years after follow-up after total meniscectomy, the incidence of degenerative arthritis as documented by X-ray was 300% more likely in the knee that had the meniscectomy versus the nonoperated knee.⁶⁴

Joint instability is a common result of meniscectomy, which is not surprising considering that the meniscus is a primary stabilizing component of the knee. One of the principle reasons for meniscal operation is to improve joint stability, yet meniscectomy often appears to have the opposite effect, eliciting even more instability, crepitation, and degeneration than the injury 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.^65-67 A knee joint becomes unstable when ligaments, cartilages, or bone structures are weakened and unable to carry out the level of function of a healthy knee. Such is the case when the meniscus is removed from the knee and unable to perform the usual weight-bearing and tracking functions, placing additional stress on the rest of the knee.^68-69Common physical symptoms of instability after meniscectomy are crepitation, such as cracking or popping, and locking (see loose bodies) in the joint. On radiographic examination, this postoperative deterioration of the joint is evidenced by narrowing of joint space and flattening of the tibiofemoral surfaces.

Because the knee is a joint designed for rotational motion, the shape of the bone structures is a vital part of mobility, and when those rotational mechanisms are altered, proper motion is not possible, causing the crepitation in the joint. For example, one study following over 1,000 meniscectomy patients found that 10 to 20 years after the surgery, 27% had more crepitus in the knees which underwent meniscectomy than they had in the untreated knees.⁶⁶In this same group of patients, degenerative changes ranging from flattened tibial and femoral bone surfaces to significant joint space narrowing were found in 62.5% of the patients with X-ray evaluation of their knees. These researchers concluded that there was a direct correlation between the degeneration of these tibiofemoral surfaces and complaints on clinical examination.⁶⁵ A similar study found that 10 years after undergoing meniscectomy, 65% of patients had radiographic evidence of joint space narrowing greater that 50%.⁶⁹ The greatest risk of partial and total meniscectomy is in the development of long term degenerative osteoarthritis. Numerous studies have confirmed that a large percentage of the meniscectomy population experience joint osteoarthritis later in life.^70-76 One study found that 15 to 22 years after having a meniscectomy, the odds ratio of knee degenerative arthritis was 2.6 after medial meniscectomy and 5.3 after lateral meniscectomy, using the non-operated knee as the control.⁷¹ In one study, 20 to 29 years after meniscectomy, X-rays showed 53% had significant progression of degenerative arthritis compared to 13% of the nonoperated knees.⁷² Another group of researchers found that 21 years after meniscectomy, 71% of operated knees showed signs of at least mild degeneration and 48% showed signs of moderate or severe joint degeneration.⁷⁴ Another study found that 40% of meniscectomies resulted in degenerative osteoarthritis, and many were accompanied by other injuries, including a large number of ligament tears.⁷⁵

One study noted, that “although risk factors for post-traumatic osteoarthritis are multifactorial, the primary risk factor that stood out in this study was if a meniscectomy had been performed.” In this study the risk of developing osteoarthritis in the knee after meniscectomy was 100%.⁷⁶Biomechanically, the development of osteoarthritis can be explained, in part, by the increased stress placed on the tibia and femur post meniscectomy. It is a known fact that reducing the size of contact area on a surface increases pressure in the remaining area. Therefore, by removing all or part of the meniscus from the knee, the area through which weight is transmitted in the joint is reduced, thus increasing the pressure on both the tibia and the femur, and their articular cartilage. The amount of contact stress on the tibiofemoral joint can increase by 65% with only a 10% reduction in contact area, and this percentage increases in proportion to the amount of meniscus removed. Complete removal of the meniscus can increase contact stress by as much as 700%.^74-77

(See Figure 10.) What this means for any knee without a meniscus is that it now bears the pressure proportional to carrying seven extra people on one knee. An additional aspect contributing to the acceleration of the osteoarthritic process is through structural wear of the articular cartilage. (See Figure 11.) By depriving the joint of the ability to lubricate the articular cartilage, the motion of the femur against the tibia will begin to break down the cartilage. When these articular cartilage cells, which are metabolically active, degenerate faster than they can regenerate, the result is the accelerated breakdown (degeneration) within the joint.⁷⁷One study which followed rabbits in three-month intervals after varying levels of injury, found that the amount of cartilage damage sustained was greatest in the meniscectomy subjects, proving this treatment to be even more damaging than joint instability is a common result of meniscectomy.

Although osteoarthritis (OA) may have a reputation as a slowly developing disease only prevalent in the elderly, this is clearly not the case. Cartilage loss can develop from adolescent injuries and appear as early as a few years after a meniscectomy.^78-81 Precursors to OA, such as evidence of biological cartilage alterations, can appear in as little as three months post meniscectomy.^82-83 Because OA develops steadily with time, this can have devastating effects by just five to 10 years after the procedure. The articular cartilage in a knee deteriorates at an average rate of 4.1% per year after meniscectomy.⁸⁴ This rate is about twice the rate of normal cartilage loss with aging.⁸⁵ After OA forms, the articular cartilage continues to deteriorate in the knee joint at a rate of about four to five percent per year.^86-87 The results of total meniscectomy have led to a more cautious approach to meniscal excision, particularly with surgical techniques removing only the damaged portion of the meniscus.^85-88 The thought is that if a portion of the meniscus is preserved, then meniscal function will be more normal as well.

Studies have confirmed that removing only the torn portion of a meniscus lowers the severity of postoperative complications, shortens the length of hospital recovery and therapy, and reduces overall pain levels, but the nature of postoperative complications remains the same. These risks include degenerative osteoarthritis, joint instability, femoral and tibial surface damage, and risk of re-injury requiring re-operation.^87-88

Partial meniscectomy, like total meniscectomy, was found via MRI volume measurement to cause cartilage loss at a rate of 4.1% per year; a rate that is 78% faster than controls.⁸⁹ Other researchers noted when meniscal integrity is compromised, such as with partial meniscectomy, the likelihood of developing degenerative arthritis is large.^90-91 One of the main reasons for this, is that partial meniscectomy by definition puts additional strain on the ligamentous support of the knee to provide stability. Follow-up studies, show that Ligament laxity in the medial and lateral collateral ligaments and anterior cruciate ligaments is increased with meniscectomies.^92-94 In regard to degenerative symptoms, one study reported that one year after undergoing an operation, 9% of partial meniscectomy patients experienced functional impairment, versus 28% of total meniscectomy patients. Almost seven years later, these numbers had increased to 62% in partial meniscectomy patients and 52% in total meniscectomy patients.⁹⁵McGinity et al. documented in his study of post surgical function that “athletes who have undergone partial meniscectomy and total meniscectomy were equally likely to give up sports altogether as a direct result of the operation.”⁹⁶

As the importance of maintaining complete intact menisci has become more widely recognized, the desire for a less invasive and more curative treatment has been sought out for meniscal injuries. For this reason, many have turned to meniscal repair as their treatment of choice. Meniscal repair utilizes one of several suturing techniques to reattach a torn flap of the meniscus, rather than removing it. In preparation for meniscal repair, the meniscus is generally debrided to remove any tissue that is rendered too loose or “contaminated” to heal, and then the procedure is performed either open or through incision under knee arthroscopy.⁹⁷ Meniscal repair is generally reserved for peripheral tears that extend into the red zone, because the likelihood of healing is greater in that region.^97-98 The short-term results of meniscal repair have varied significantly, with a range of both promising and disappointing outcomes.^99-100 As the ability to track long-term results has become possible, repair failures and associated symptoms have been observed in large numbers, proving the effectiveness of this treatment to be questionable at best. Preoperative symptoms have been shown to resurface as early as six months following meniscal repair, and can lead to long-term joint damage prevalent decades later.^101-102Specifically, as documented by CT arthrogram, completely healing from meniscal repair was found in only 58% of the menisci.¹⁰¹ After a 13 year follow-up the failure rate in one Swedish study was 29%.¹⁰² In this same study, knee function showed a statistically significant decline in the meniscal-repaired knee compared to the non-operated knee. The authors noted, “We conclude that 13 years after repair, knee function is good but not better than after meniscectomy and not as good as in an uninjured knee.” A failed meniscal repair is generally defined as lack of improvement after operation or, more specifically, any re-injury and subsequent re-operation. Re-injury after meniscal repair is not uncommon, affecting the original site of injury as well as new areas of the meniscus.

Six independently performed studies, conducted an average of eight years after a repair, found that 10% to 38% of all meniscal repairs were considered failures.^103-108 The 38% failure rate was in patients under the age of 18. It is also worth noting that these injuries were not isolated, but in many cases occurred in addition to the return of multiple preoperative symptoms, such as joint pain, instability, weakness, and swelling. In summary, it can be concluded that about 25% of all meniscal repairs are failures. In more practical terms, for 25% of all patients undergoing meniscal repair, the surgery will either not relieve their symptoms or the repair will fail and their symptoms will again return and need another operation or some other form of therapy. For instance, in one study, meniscectomy was needed in 10% of the patients after meniscal repair.¹⁰⁹ Considering the average follow-up for these groups of studies was eight years, imagine what the failure rate of meniscal repairs would be at 16 or 24 years! Another concern associated with meniscal repair is, not surprisingly, long-term degenerative osteoarthritis.^109-112

This makes sense since a great percentage of meniscal repairs do not heal completely. One study found that only 30% of patients after meniscal repair showed no signs of osteoarthritis, whereas 83% of patients exhibited no signs of osteoarthritis before the treatment.¹⁰⁹ Although meniscal repair is most frequently performed in regions of greater vascularity, the treatment does not actually stimulate meniscal healing through vascular supply.¹¹⁰ There was a 12% re-injury rate after meniscal repair in this study. The most recent contribution to surgical treatment of meniscus injuries has been the advent of the meniscal transplant. Transplantation can be performed either with human allograft or artificial collagen implants, with the majority utilizing deep-frozen cryopreserved allografts extracted from human cadaver knees. Before a transplant can be conducted, the patient must undergo arthroscopic removal of any remaining meniscal tissue to prepare for the new implant. Using one of two techniques, a bone plug or a bridge, the implant is then placed inside the knee in alignment with the femur and tibia, and then sutured into place. This procedure requires careful measurement of the meniscus and precision in matching the size and placement of a new meniscus, as even the slightest error in measurement could cause improper tracking and damage to the knee.¹¹³ This method has been monitored closely for short-term results, but because it is a relatively new treatment and methods between studies have varied, long-term results are difficult to assess. Based on what information we do have, however, hope for long-term relief remains questionable. In a number of studies spanning from two to seven years after allograft transplantation, failure rates ranged from 28% to 58%, where symptoms such as allograft deterioration, new tears, and unresolved pain symptoms resulted in premature removal of allografts or additional arthroscopic surgeries.^113-115 As one study states, “[patients] should be advised that the procedure is not curative in the long term, and additional surgery will most likely be required.”¹¹³ (See Figure 12.)

Recovery time is another important issue in assessing any treatment, and transplants have a longer rehabilitation time than other meniscal operations. In documented transplantation cases, patients did not begin physical rehabilitation until eight weeks post operation, at which time they were started on non-strenuous activities such as cycling, followed by swimming and walking, between nine and 12 weeks post operation. Even in the most successful knees, patients were informed that they should never return to arduous physical activity, including athletics.¹¹⁴ Meniscal transplantation with such a high failure rate, diminishes the hope that anyone, especially athletes, would have for maintaining an active lifestyle. Although there is some short term improvement in aspects such as pain control, the long term effects of meniscectomy, meniscal repair, and meniscal allograft transplantation reveal that symptoms, such as pain and instability, will persist for years afterward. The main reason that these and other treatments are ineffective in healing the meniscus can simply be attributed to the fact that, regardless of what is done to structurally repair the meniscus, it is still primarily an avascular cartilaginous structure which cannot heal without a sufficient supply of nutrition. The poor healing potential of meniscal tears has led to the investigation of methods to provide blood supply to the injured area. The methods include vascular access channels and synovial pedicale flaps. Unfortunately, no surgical treatment to date has been shown to stimulate healing of the meniscus. On the contrary, surgeries often have the opposite effect. They initiate additional damage to the joint, further decreasing the probability of healing. Current surgical techniques for meniscal injuries accelerate menisci and joint degeneration. Perhaps Lohmander et al. in their comprehensive review of surgical procedures for meniscal pathology said it best, “there is a lack of evidence to support a protective role of repair or reconstructive surgery of the anterior cruciate ligament or meniscus against osteoarthritis development…Osteoarthritis developed in the injured joints is caused by intraarticular pathogenic processes initiated at the time of injury, combined with long-term changes in dynamic joint loading.”¹¹⁶ The bottom line is surgical procedures do not initiate the regenerative process needed in these traumatized knee joints. Left alone or treated by the surgery, the degenerative process initiated by the initial trauma continues, unless something is done to initiate regeneration. The reverse of degeneration is simply regeneration. In other words, a degenerative process can only be reversed when stimulated to repair itself. Degeneration of the meniscus is initiated by a damaged meniscus’ inability to repair itself, and the surgical procedures themselves accelerate the degenerative process. The ideal treatment for the damaged meniscus is one that can stimulate regeneration of the degenerated or torn meniscus. The injection technique whereby the proliferation of cells is stimulated via growth factor production is called Prolotherapy. (See Figure 13.)

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 type of blood cell called platelets, rush to the area to cause 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, and then release growth factors, primarily from the alpha granules. At this point, the healing process then proceeds in three simple stages: inflammatory, fibroblastic, and maturation. After growth factors are released from the platelets, they stimulate the inflammatory stage, each growth factor playing a key role. (See Figure 14.)

This stage is marked by the appearance of monocytes which are white blood cells that respond quickly to inflammatory signals and elicit an immune system 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 material 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. In the case of the injured meniscus, it is clear that the damaged tissue can not repair itself. Healing in the meniscus depends on the having enough of a blood supply and/or growth factors at the site of the injury. Since less than 20% of the meniscus is vascularized by the time a person reaches the age of 40 years, meniscal healing is generally incomplete.¹¹⁷

Once torn, the menisci, because of its low cellularity and incomplete healing response, is unable to fully repair itself.^118-119 In one study, upon a five-year follow up after meniscal allograft transplantation, transplanted menisci were found to have decreased growth factor production indicating decreased biological function. Furthermore, the transplanted menisci were repopulated with fewer cells than even an untreated torn meniscus.^1120-121 It has also been shown that the number of cells in the meniscus decreases with age.¹²²

In Vivo and In Vitro Studies on Growth Factors in Stimulating Meniscal Repair
Because growth factors are known to be a basic component of healing, the adjunct use of growth factors to stimulate connective tissue repair has been studied as a potential for the treatment of injured soft tissues, including the meniscus. Direct exposure of connective tissues to fibroblastic growth factors can indeed cause new cell growth and formation of collagen. Therefore, injecting growth factors at the site of a soft tissue injury allows the damaged tissue to heal itself. Before any treatment is tested on humans, it is common practice to investigate the effect of that treatment, in this case growth factors, on cells (see side bar), as well as on animal models with similar pathology to humans. The primary objective of these studies is to determine if and how a poorly vascularized tissue, such as the meniscus, can be stimulated for reliable cellular and tissue repair. In such studies, growth factors, such as the ones extracted and secreted from the platelets are incubated with meniscal cells and then injected into injured meniscal tissue to see if cellular repair and regeneration occurs. Many studies demonstrate that injection of various growth factors can increase meniscal cell activity and stimulate repair, in this tissue and other connective tissues.^123-140 As with other tissues that have a poor blood supply, like cartilage, meniscal cells are sparse. They are best categorized as fibrochondrocytes, as they have cellular characteristics of chondrocytes (see research paper), cartilage cells, and fibroblasts that synthesize connective tissues such as ligaments.¹⁴¹ The meniscal cells are responsible for maintaining the extracellular matrix. The ideal mode of treatment for meniscal tears and degeneration would stimulate the production of meniscal fibrochondrocytes and its synthesis of extracellular matrix (ECM). Increased ECM synthesis would render the generated meniscal tissue more able to withstand the forces placed on the knee. For it is the collagen, proteoglycans and glycoproteins in the ECM which give the meniscus its compressive properties to withstand tensile loads.¹⁴² Platelet-derived growth factor (PDGF) is one growth factor commonly used in animal meniscus studies. One recent study measured both cell proliferation and extracellular collagen matrix formation in each of the inner, middle, and outer regions of sheep menisci, in the presence of PDGF-AB. After one week, meniscal cell proliferation was apparent in all three meniscal zones, reaching an 800% increase in the inner vascular zone compared to control. The formation of the collagen matrix had increased by 450% in the middle zone and by 300% in the outer zone. (See Figure 15.)

An increase in the production of glycosaminoglycans, a main component of synovial fluid, in each of the three zones was observed.¹³² Meniscal cell migration was also stimulated. A similar in vitro study found that cell production of sheep menisci increased with proportion to the increased concentration of PDGF-AB used. This study observed a 2.5-fold increase in cell production.¹³³ Another in vitro study placed bovine meniscal cells in different solutions containing cytokines and measured the effect of each on the synthesis of new cells in each of the three meniscal zones. The authors reported that significant DNA synthesis occurred in meniscal cells treated with PDGF-AB, hepatocye growth factor, and bone morphogenic protein-2, in all three regions.¹³⁴ Similar results were found when analyzing the effect of basic fibroblastic growth factor (bFGF) on meniscal cells from sheep. When cultured in the bFGF, the formation of DNA increased by as much as sevenfold, and protein synthesis increased by as much as 15- fold in the inner (avascular) zone of the meniscus. The results of the outer and middle zones likewise yielded statistically significant cell growth.^135,138 The synthesis of proteoglycans, the principle component of the extracellular collagen matrix, was specifically measured in another study on sheep menisci. In all meniscal zones, transforming growth factor beta (TGF-β) stimulated Proteoglycan production by up to 100% and the proteoglycans were larger than controls. TGF-β also stimulated cell division in the fibrochondrocyte cultures.¹³⁷Other authors have also confirmed that meniscal fibrochondrocytes from all three zones, including the avascular zone, can proliferate and generate new extracellular matrix given the proper stimuli.^{128, 129, 139, 140} Such findings have been the basis of the integration of growth factors in the treatment of meniscal pathology. in vivo - experimentation done on live isolated cells. in vitro - experimentation done in an artificial environment outside the living organism.

One study involved the use of growth factors TGF-β1 and Insulin-like growth factor-1 (IGF-1) as an aid in the insertion of meniscal plugs into the avascular portion of the meniscus. This study found that TGF-β1 was effective in forming an attachment between the actual meniscus and the plugs, and IGF-1 was effective in cell proliferation. Both growth factors also significantly increased the cell density of the plugs.¹²⁷ Canine menisci with a defect in the avascular portion documented a 10-fold increase in healing by the addition of a fibrin sealant and endothelial cell growth factor.¹³⁷ In this study, the ingrowth of new blood vessels (neovascularization) and granulation tissue (connective tissue) to the avascular portion of the meniscus was noted. Growth factors have even been introduced into surgical treatments, particularly meniscal transplantation, to preserve and enhance joint tissue.^143-144 The evidence that avascular cells are capable of regeneration, when properly stimulated to do so, serves as the basis and rationale for Prolotherapy in the treatment of meniscal pathology.

Prolotherapy Stimulates Growth Factor Formation
The primary objective of Prolotherapy injections is to initiate or recreate the inflammatory stage of the healing process. It does so by raising the levels of growth factors to resume or initiate a repair sequence that has prematurely aborted or never started.¹⁴⁵ Cells in the area of exposure, such as fibroblasts, chondrocytes and fibrochondrocytes, can also be expected to respond if the growth factors are those that proliferate such cells.¹⁴⁶

By triggering this cascade of anabolic events, Prolotherapy stimulates the new growth of cells and is indirectly responsible for rebuilding depleted tissues. Typical Prolotherapy solution use a hypertonic solution of dextrose (glucose) as its base. Studies have shown that even a brief exposure to small amounts of glucose molecules causes an elevation in growth factors such as IGF-1, TGF-β, TFG-β, bFGF, and PDGF-B.^145-150

Another substance used in Prolotherapy, especially for degenerative knee conditions, is human growth hormone (HGH).¹⁵¹ HGH stimulates the production of IGF-1 in the liver, but it can also have an important role in the localized treatment of degenerate cartilage cells. Circulating and locally produced IGF-1 can stimulate DNA synthesis, cell replication, and proteoglycan and glycosaminoglycan synthesis in articular chondocytes.¹⁵² Additional studies show that HGH and IGF-1 have both been shown to cause growth and repair of articular cartilage cells.^153-155 One reason for this cartilage growth can be that cartilage cells have HGH receptors.¹⁵⁶ Anecdotal radiographic evidence of the regeneration of articular cartilage has been seen with and without the use of HGH with Prolotherapy to the knee.^157-158

Other published studies have documented symptomatic improvement in patients with degenerative knee arthritis with Prolotherapy.^159-161 Another emerging technique in the field of Prolotherapy is Platelet Rich Plasma Prolotherapy (PRPP), which utilizes the injection of human autologous blood components to facilitate healing of degenerative tissue injuries. In this technique a small amount of whole blood is drawn and is separated into platelet poor plasma and platelet rich plasma. The latter is used in PRPP and consists of plasma, which is the liquid component of blood, containing a high concentration of platelets. Because platelets are the storehouses of growth factors, platelet rich plasma is abundant in growth factors. PRPP though not only provides a higher concentration of growth factors to the tissue than is provided by normal blood supply, it stimulates the injured tissues to increase their own innate growth factor production.^162-164 PRPP has shown in one controlled study to give statistically significantly better results for knee osteoarthritis then hyaluronan injection.¹⁶⁵ In actual clinical practice, there are a host of solutions available to the doctor performing Prolotherapy. Although there have been no studies to date directly addressing the use of Prolotherapy for meniscal injuries, Prolotherapy has a long history of treating degenerative knee conditions including meniscal pathology.^166-169

For seventeen years the primary author (R.H.) has treated meniscal pathology successfully with Prolotherapy. This retrospective study was done to document the degree of improvement in meniscal tears and degeneration with Prolotherapy.

Patients and Methods
All patients were treated at the primary author’s private practice, Caring Medical and Rehabilitation Services in Oak Park, Illinois. A premedical student (H.M.) reviewed in-house medical charts of patients who had completed their last Prolotherapy treatment at least one year ago and had MRI documented meniscal pathology. This criterion was chosen to give adequate time to determine if the positive effects of the Prolotherapy treatments continued once they were finished. H.M. completed phone interviews asking the patients a series of questions with an emphasis on the effect Prolotherapy had on their knee pain, stiffness, and quality of life. All patients received the Hackett-Hemwall technique of dextrose Prolotherapy to the knee. This included a 15% dextrose, 10% Sarapin and 0.2% lidocaine solution as the base solution. Each patient was given an intraarticular injection of 5-10cc of solution. Twenty-four of 28 knees received 2IU of human growth hormone added to this base solution. Two patients received 3.5cc of Platelet Rich Plasma Prolotherapy (PRPP) injected inside the joint. One patient received only base solution and one patient received manganese as an additive. Prolotherapy injections were also given along the tender points about the knee, including the medial collateral ligament. Patients typically received a total of 30-40cc of solution per treatment visit. Patients were seen every four to six weeks. (See Figure 16.) All data was analyzed by an independent computer consultant (D.G.), who had no previous knowledge of Prolotherapy. A matched sample paired t-test was used to determine statistically significant improvements in the before and after Prolotherapy measurements for pain and stiffness.

Patient Characteristics
Data was tabulated on 28 knees in 24 patients. Of the 24 patients, 71% (17) were male and 29% (7) were female with an average age of 45 years. Eighteen knees had MRI documented meniscal tears of which eight were acute and ten were chronic (over six months since the tear). The medial meniscus was torn in sixteen of the knees and the lateral meniscus in two. According to the radiographic reports, four of the tears were complex, three were vertical, three were horizontal, two were bucket handle, and one was complete. The other five were nondescript meniscal tears. Arthroscopy had been previously performed on ten of the knees. Ten of the knees had MRI documented meniscal degeneration without tears. (See Table 1.)

Treatment Outcomes
Patients received an average of 6.2 Prolotherapy treatments per knee. The average time since their last Prolotherapy treatment was 18.6 months. Patients were asked to rate their knee pain, stiffness, and crepitation (crunching sensation) levels on a scale of 0 (none) to 10 (severe crippling). For the 28 knees the average starting pain level was 7.2, stiffness 5.8, and crepitation 4.9 which improved to levels of 1.6, 2.0, and 2.5 respectively, after Prolotherapy. (See Figure 17.) Before Prolotherapy, 17 patients were taking one or more pain medication, but after Prolotherapy only three were taking one pain medication.

Patients were also asked to rank their knee range of motion with 0 being normal motion and 10 representing no motion. The average range of motion improved from a level of 4.1 to 1.1 after Prolotherapy. Only 25.9% of the patients had normal motion (0 or 1) before Prolotherapy, but after Prolotherapy this increased to 75%. Before Prolotherapy only four (14.3%) patients had normal walking ability (0% compromised), but this increased to 20 (71.4%) after Prolotherapy. (See Figure 18.) In regard to exercise ability, before Prolotherapy 14.2% of patients could exercise greater than 60 minutes, but after Prolotherapy this increased to 85.7%. (See Figure 19.) In regard to the question “Did the improvements with Prolotherapy last?” 96.4% of the patients stated they still have lasting pain relief in their knees as a result of the Prolotherapy. Eighty-six percent reported lasting improvement in stiffness, while 100% of the patients noted their improvement in walking ability continues to this day. To the question “Did Prolotherapy meet your expectations?” 96.4% (27 out of 28) of the patients treated answered “yes.” In regard to the question “Did you end up getting surgery on your knee?” only one patient answered “yes.”

Statistical Analysis
A matched sample paired t-test was used to calculate the difference in responses between the before and after measures for pain and stiffness for the 24 patients (representing 28 knees). Using the paired t-test, the p values for pain and stiffness for the two groups reached statistical significance to the p<.000001 level.

DISCUSSION: Principle Findings
The results of this pilot, retrospective, uncontrolled study show that Prolotherapy helps decrease pain and stiffness and improve the quality of life in patients with meniscal tears and degeneration. This includes tears in all three meniscal zones, as well complete and complex meniscal tears. The Hackett-Hemwall dextrose Prolotherapy, including those with human growth hormone or platelet rich plasma added to the intraarticular injection, improved pain and stiffness to a statistically significant level. From the patient’s point of view there were noticeable improvements in crepitation and range of motion of their knees. Ninety-six percent (27 out of 28 knees) improved to the point that the patients felt that Prolotherapy met their expectations and no surgery for meniscal pathology was needed. Major improvements in other quality of life issues, including walking ability, exercise ability, and decreased medication usage was also reported with Prolotherapy. One patient underwent a total knee replacement in February 2010. In reviewing this patient’s chart, his initial MRI revealed “a degenerative tear involving the anterior horn and body of the lateral meniscus which extends in a longitudinal fashion to the apex and superior surface.” The patient’s dates of Prolotherapy treatment were 10/18/06, 2/5/07, 3/19/07 and 7/26/07. At the third visit he said his overall improvement was 70% and at his last visit his overall improvement was 80%. He was not seen after 7/26/07. While this patient ended up needing a total knee replacement in February 2010, our review found that the patient did not comply with the recommended Prolotherapy treatment course, to be received every four to six weeks until his pain resolved or he was satisfied with the improvements. It is not known why this patient did not continue to follow-up and receive more Prolotherapy after the July 2007 visit, if his pain returned, as reported. While this study cannot be compared to a clinical trial in which an intervention is investigated under controlled conditions, clearly the findings are extremely positive. The level of improvement with pain and stiffness met a highly statistically significant level and more importantly the Prolotherapy met the expectations of the patient in 27 of 28 knees to the point that surgery was not required. The marked decrease in pain and stiffness was accompanied by similar improvements in walking and exercise ability, suggestive that the Prolotherapy was indeed repairing the meniscus tear. Another plausible explanation for the extremely high success rate of this study is that the treatment given was Hackett-Hemwall Prolotherapy. In this type of Prolotherapy, not only are the meniscal injuries treated, but also any joint instability, ligament weakness or tear, as well as any tendinopathy.

In regard to the patients with degeneration of the menisci, Prolotherapy strengthened the menisci to the point that they could function properly under load. As previously mentioned, various types of tears were treated and showed improvement with Prolotherapy, including the tears of the white zone (with little or no blood supply). One reason to do this study was to determine if a certain type of meniscal tear did not respond to Prolotherapy. But in this pilot study, all type of tears (including vertical, horizontal, complex and oblique) and locations (lateral, medial, posterior, and anterior) responded. In the future, MRI documentation of meniscal repair with Prolotherapy would confirm these conclusions.

CONCLUSIONS The Hackett-Hemwall technique of dextrose Prolotherapy used on patients with MRI documented meniscal pathology including tears and degeneration, interviewed an average of 18 months after their last Prolotherapy treatment, was shown in this retrospective pilot study to improve patients’ quality of life. Most patients reported statistically significantly less pain and stiffness and major improvements in range of motion, crepitation of the knee, medication usage, walking ability, and exercise ability. The improvements with Prolotherapy met the expectations of the patients in over 96% of the knees to the point where surgery was not needed. Prolotherapy improved knee pain and function regardless of the type or location of the meniscal tear or degeneration. The improvements were so overwhelmingly positive that Hackett-Hemwall Prolotherapy should be considered as a first-line treatment for pain and disability caused by meniscal tears and degeneration. If these results are confirmed by further studies under more controlled circumstances, with larger patient populations, and with MRI confirmation, surely Hackett-Hemwall Prolotherapy will become a first-line treatment for meniscal tears and degeneration.

References