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

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 longterm 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, E p i D E M i o l o g y o F M E n i s c a l i n j u r i E s K nee 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 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. Journal of Prolotherapy. 2010;2(3):416-437. KEyWorDs: human growth hormone, meniscal degeneration, meniscal tear, meniscus, platelet rich plasma, prolotherapy.

[1]  A V Swan,et al.  Late degenerative changes after meniscectomy. Factors affecting the knee after operation. , 1984, The Journal of bone and joint surgery. British volume.

[2]  K. Messner,et al.  The menisci of the knee joint. Anatomical and functional characteristics, and a rationale for clinical treatment , 1998, Journal of anatomy.

[3]  G. Scott,et al.  Combined posterior incision and arthroscopic intra-articular repair of the meniscus. An examination of factors affecting healing. , 1986, The Journal of bone and joint surgery. American volume.

[4]  W. Petersen,et al.  Age-related blood and lymph supply of the knee menisci. A cadaver study. , 1995, Acta orthopaedica Scandinavica.

[5]  J. Gillquist,et al.  Results of open meniscus repair. Long-term follow-up study with a matched uninjured control group. , 2000, The Journal of bone and joint surgery. British volume.

[6]  C. Helms,et al.  MR imaging of the knee: findings in asymptomatic collegiate basketball players. , 2002, AJR. American journal of roentgenology.

[7]  J. Cook The current status of treatment for large meniscal defects. , 2005, Clinical orthopaedics and related research.

[8]  B. Gansbacher,et al.  Second generation of meniscus transplantation: in-vivo study with tissue engineered meniscus replacement , 2006, Archives of Orthopaedic and Trauma Surgery.

[9]  J. Jackson,et al.  Degenerative changes in the knee after meniscectomy. , 1968, British medical journal.

[10]  J. Lysholm,et al.  Suture of new and old peripheral meniscus tears. , 1983, The Journal of bone and joint surgery. American volume.

[11]  A. Hede,et al.  Articular cartilage changes following meniscal lesions. Repair and meniscectomy studied in the rabbit knee. , 1991, Acta orthopaedica Scandinavica.

[12]  A. Hede,et al.  Epidemiology of meniscal lesions in the knee. 1,215 open operations in Copenhagen 1982-84. , 1990, Acta orthopaedica Scandinavica.

[13]  W. D. Cannon,et al.  Meniscus Tears: Treatment in the Stable and Unstable Knee , 1993, The Journal of the American Academy of Orthopaedic Surgeons.

[14]  D. Jo,et al.  The Effects of Prolotherapy on Knee Joint Pain due to Ligament Laxity , 2004 .

[15]  E. Rohren,et al.  Discoid lateral meniscus and the frequency of meniscal tears , 2001, Skeletal Radiology.

[16]  B. Morrey Prevalence of Tibiofemoral Osteoarthritis 15 Years After Nonoperative Treatment of Anterior Cruciate Ligament Injury: A Prospective Cohort Study , 2009 .

[17]  E. Roos,et al.  Knee osteoarthritis after meniscectomy: prevalence of radiographic changes after twenty-one years, compared with matched controls. , 1998, Arthritis and rheumatism.

[18]  P. Jokl,et al.  Meniscal abnormalities in the asymptomatic population at MR imaging. , 1990, Radiology.

[19]  E. Anitua,et al.  Intra-articular injection of an autologous preparation rich in growth factors for the treatment of knee OA: a retrospective cohort study. , 2008, Clinical and experimental rheumatology.

[20]  Russell F. Warren,et al.  Microvasculature of the human meniscus , 1982, The American journal of sports medicine.

[21]  M. Bhargava,et al.  The Effect of Cytokines on the Proliferation and Migration of Bovine Meniscal Cells , 1999, The American journal of sports medicine.

[22]  J. J. Niebauer,et al.  The Healing of Semilunar Cartilages , 1936 .

[23]  Stephen W Marshall,et al.  Descriptive epidemiology of collegiate women's soccer injuries: National Collegiate Athletic Association Injury Surveillance System, 1988-1989 through 2002-2003. , 2007, Journal of athletic training.

[24]  A. Scala,et al.  Different patterns of meniscal tears in acute anterior cruciate ligament (ACL) ruptures and in chronic ACL-deficient knees , 2005, Knee Surgery, Sports Traumatology, Arthroscopy.

[25]  K. Shelbourne,et al.  Repair of Locked Bucket-Handle Meniscal Tears in Knees with Chronic Anterior Cruciate Ligament Deficiency , 2003 .

[26]  E. Wojtys,et al.  Arthroscopic meniscal repair evaluated by second-look arthroscopy , 1991, The American journal of sports medicine.

[27]  J. Noble Lesions of the menisci. Autopsy incidence in adults less than fifty-five years old. , 1977, The Journal of bone and joint surgery. American volume.

[28]  M. Majewski,et al.  Epidemiology of athletic knee injuries: A 10-year study. , 2006, The Knee.

[29]  T. Wickiewicz,et al.  Meniscal tears in the athlete. Operative and nonoperative management. , 2000, Physical medicine and rehabilitation clinics of North America.

[30]  F. Forriol,et al.  In vitro healing of avascular meniscal injuries with fresh and frozen plugs treated with TGF-beta1 and IGF-1 in sheep. , 2008, International journal of clinical and experimental pathology.

[31]  A. Barkan Acromegalic arthropathy and sleep apnea. , 1997, The Journal of endocrinology.

[32]  S. Luhmann Acute Traumatic Knee Effusions in Children and Adolescents , 2003, Journal of pediatric orthopedics.

[33]  Ali Guermazi,et al.  Incidental meniscal findings on knee MRI in middle-aged and elderly persons. , 2008, The New England journal of medicine.

[34]  T. Fairbank Knee joint changes after meniscectomy. , 1948, The Journal of bone and joint surgery. British volume.

[35]  K. Shelbourne,et al.  MR imaging of the knee: pseudotear of the lateral meniscus caused by the meniscofemoral ligament. , 1990, AJR. American journal of roentgenology.

[36]  C. McDevitt,et al.  The ultrastructure and biochemistry of meniscal cartilage. , 1990, Clinical orthopaedics and related research.

[37]  C. Stanitski Correlation of Arthroscopic and Clinical Examinations With Magnetic Resonance Imaging Findings of Injured Knees in Children and Adolescents , 1998, The American journal of sports medicine.

[38]  Jack Farr,et al.  Tibiofemoral Contact Mechanics after Serial Medial Meniscectomies in the Human Cadaveric Knee , 2006, The American journal of sports medicine.

[39]  R. Webber,et al.  Cell culture of rabbit meniscal fibrochondrocytes: Proliferative and synthetic response to growth factors and ascorbate , 1985, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[40]  Kyriacos A Athanasiou,et al.  Effects of growth factors on meniscal fibrochondrocytes. , 2005, Tissue engineering.

[41]  F. Noyes,et al.  Arthroscopic Repair of Meniscal Tears that Extend into the Avascular Zone , 1998, The American journal of sports medicine.

[42]  C. Starkey,et al.  Injuries and illnesses in the national basketball association: a 10-year perspective. , 2000, Journal of athletic training.

[43]  F. Cicuttini,et al.  Rate of knee cartilage loss after partial meniscectomy. , 2002, The Journal of rheumatology.

[44]  C. Sledge Growth hormone and articular cartilage. , 1973, Federation proceedings.

[45]  Michael B. Gerhardt,et al.  Platelet rich plasma injection grafts for musculoskeletal injuries: a review , 2008, Current reviews in musculoskeletal medicine.

[46]  Wenchao Wu,et al.  High glucose upregulates connective tissue growth factor expression in human vascular smooth muscle cells , 2007, BMC Cell Biology.

[47]  N. Tumia,et al.  Platelet derived growth factor-AB enhances knee meniscal cell activity in vitro. , 2009, The Knee.

[48]  Á. Osti [On the discoid meniscus]. , 1967, L' Arcispedale S. Anna di Ferrara.

[49]  J B Finlay,et al.  The effect of medial meniscectomy on strain distribution in the proximal part of the tibia. , 1984, The Journal of bone and joint surgery. American volume.

[50]  C. Pfirrmann,et al.  Patients with suspected meniscal tears: prevalence of abnormalities seen on MRI of 100 symptomatic and 100 contralateral asymptomatic knees. , 2003, AJR. American journal of roentgenology.

[51]  Rodkey Wg Basic biology of the meniscus and response to injury. , 2000 .

[52]  G. Romeo,et al.  Increased activity of the insulin-like growth factor system in mesangial cells cultured in high glucose conditions. Relation to glucose-enhanced extracellular matrix production , 1996, Diabetologia.

[53]  E. Roos,et al.  Joint injury causes knee osteoarthritis in young adults , 2005, Current opinion in rheumatology.

[54]  F. Cicuttini,et al.  Factors influencing longitudinal change in knee cartilage volume measured from magnetic resonance imaging in healthy men , 2005, Annals of the rheumatic diseases.

[55]  D B Kettelkamp,et al.  Factors effecting late results after meniscectomy. , 1974, The Journal of bone and joint surgery. American volume.

[56]  K. Spindler,et al.  Regional mitogenic response of the meniscus to platelet‐derived growth factor (PDGF‐AB) , 1995, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[57]  R. L. Smith,et al.  Growth hormone stimulates insulin‐like growth factor I actions on adult articular chondrocytes , 1989, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[58]  Felix Eckstein,et al.  Relationship of meniscal damage, meniscal extrusion, malalignment, and joint laxity to subsequent cartilage loss in osteoarthritic knees. , 2008, Arthritis and rheumatism.

[59]  J. Farr,et al.  Current Meniscal Allograft Transplantation , 2004 .

[60]  T. Cheng,et al.  Overview of Injuries in the Young Athlete , 2003, Sports medicine.

[61]  J. Andrish Meniscal Injuries in Children and Adolescents: Diagnosis and Management , 1996, The Journal of the American Academy of Orthopaedic Surgeons.

[62]  Kelly R McCormick,et al.  Meniscal repair of the knee. , 2009, Orthopedics.

[63]  E. R. V. van Arkel,et al.  Survival analysis of human meniscal transplantations. , 2002, The Journal of bone and joint surgery. British volume.

[64]  R. Warren,et al.  Meniscal injury and repair: clinical status. , 2000, The Orthopedic clinics of North America.

[65]  C. Krettek,et al.  The role of preoperative MRI in knee arthroscopy: a retrospective analysis of 2,000 patients , 2009, Knee Surgery, Sports Traumatology, Arthroscopy.

[66]  D. Dandy,et al.  The diagnosis of problems after meniscectomy. , 1975, The Journal of bone and joint surgery. British volume.

[67]  D. V. Davies,et al.  The blood supply of the synovial membrane and intra-articular structures. , 1948, Annals of the Royal College of Surgeons of England.

[68]  R Huiskes,et al.  Pathways of load-induced cartilage damage causing cartilage degeneration in the knee after meniscectomy. , 2003, Journal of biomechanics.

[69]  K. Søballe,et al.  Late results after meniscectomy in children. , 1987, Injury.

[70]  L. Kaplan,et al.  Incidence and variance of knee injuries in elite college football players. , 2008, American journal of orthopedics.

[71]  D G Wilder,et al.  Mechanical changes in the knee after meniscectomy. , 1976, The Journal of bone and joint surgery. American volume.

[72]  E. Freymiller Platelet-rich plasma: evidence to support its use. , 2004, Journal of oral and maxillofacial surgery : official journal of the American Association of Oral and Maxillofacial Surgeons.

[73]  M. Englund,et al.  Patellofemoral osteoarthritis coexistent with tibiofemoral osteoarthritis in a meniscectomy population , 2005, Annals of the rheumatic diseases.

[74]  P. Greis,et al.  Meniscal injury: I. Basic science and evaluation. , 2002, The Journal of the American Academy of Orthopaedic Surgeons.

[75]  C. Fink,et al.  Long-term results of arthroscopic partial lateral meniscectomy in knees without associated damage. , 2001, The Journal of bone and joint surgery. British volume.

[76]  I. Smillie,et al.  The congenital discoid meniscus. , 1948, The Journal of bone and joint surgery. British volume.

[77]  O. Brantigan,et al.  THE MECHANICS OF THE LIGAMENTS AND MENISCI OF THE KNEE JOINT , 1941 .

[78]  N. Sgaglione,et al.  Meniscus Repair and Future Directions , 2009 .

[79]  F. Guilak,et al.  Integrative repair of the meniscus: lessons from in vitro studies. , 2008, Biorheology.

[80]  M. Waters,et al.  Visual demonstration of growth hormone receptors on human growth plate chondrocytes. , 1990, The Journal of clinical endocrinology and metabolism.

[81]  F. Cicuttini,et al.  Knee cartilage loss in symptomatic knee osteoarthritis over 4.5 years , 2006, Arthritis research & therapy.

[82]  M. Hochberg,et al.  Joint Injury in Young Adults and Risk for Subsequent Knee and Hip Osteoarthritis , 2000, Annals of Internal Medicine.

[83]  D. Shakespeare,et al.  The bucket-handle tear of the meniscus. A clinical and arthrographic study. , 1983, The Journal of bone and joint surgery. British volume.

[84]  K. D. Reeves,et al.  Prolotherapy : Basic Science , Clinical Studies , and Technique , 2003 .

[86]  S. Mccormick,et al.  Modulation of wound response and soft tissue ingrowth in synthetic and allogeneic implants with platelet concentrate. , 2005, Archives of facial plastic surgery.

[87]  S. Rodeo,et al.  Allograft Meniscal Transplantation: Background, Techniques, and Results , 2002, Instructional course lectures.

[88]  I. Smillie,et al.  Studies on the chemical composition of the menisci of the knee joint with special reference to the horizontal cleavage lesion. , 1972, Clinical orthopaedics and related research.

[89]  B. F. Morrey,et al.  Growth Factors and Fibrochondrocytes in Scaffolds , 2006 .

[90]  D. H. O'donoghue,et al.  THE CLASSIC: Surgical Treatment of Fresh Injuries to the Major Ligaments of the Knee , 1950, The Journal of bone and joint surgery. American volume.

[91]  S Kashiwaguchi,et al.  MRI high-signal intensity in the menisci of asymptomatic children. , 1998, The Journal of bone and joint surgery. British volume.

[92]  N. Matsui,et al.  Repeat tears of repaired menisci after arthroscopic confirmation of healing. , 2002, The Journal of bone and joint surgery. British volume.

[93]  J. Agel,et al.  Anterior cruciate ligament injury patterns among collegiate men and women. , 1999, Journal of athletic training.

[94]  C. Clark,et al.  Development of the menisci of the human knee joint. Morphological changes and their potential role in childhood meniscal injury. , 1983, The Journal of bone and joint surgery. American volume.

[95]  N. Aigner,et al.  Two to nineteen years follow-up of arthroscopic meniscal repair using the outside-in technique: a retrospective study , 2007, Archives of Orthopaedic and Trauma Surgery.