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Plasma rich in growth factors (PRGF) as a treatment for high ankle sprain in elite athletes: a randomized control trial

  • Ankle
  • Published:
Knee Surgery, Sports Traumatology, Arthroscopy Aims and scope

Abstract

Purpose

Syndesmotic sprains are uncommon injuries that require prolonged recovery. The influence of ultrasound-guided injections of platelet-rich plasma (PRP) into the injured antero-inferior tibio-fibular ligaments (AITFL) in athletes on return to play (RTP) and dynamic stability was studied.

Methods

Sixteen elite athletes with AITFL tears were randomized to a treatment group receiving injections of PRP or to a control group. All patients followed an identical rehabilitation protocol and RTP criteria. Patients were prospectively evaluated for clinical ability to return to full activity and residual pain. Dynamic ultrasound examinations were performed at initial examination and at 6 weeks post-injury to demonstrate re-stabilization of the syndesmosis joint and correlation with subjective outcome.

Results

All patients presented with a tear to the AITFL with dynamic syndesmosis instability in dorsiflexion–external rotation, and larger neutral tibia–fibula distance on ultrasound. Early diagnosis and treatment lead to shorter RTP, with 40.8 (±8.9) and 59.6 (±12.0) days for the PRP and control groups, respectively (p = 0.006). Significantly less residual pain upon return to activity was found in the PRP group; five patients (62.5 %) in the control group returned to play with minor discomfort versus one patient in the treatment group (12.5 %). One patient in the control group had continuous pain and disability and subsequently underwent syndesmosis reconstruction.

Conclusions

Athletes suffering from high ankle sprains benefit from ultrasound-guided PRP injections with a shorter RTP, re-stabilization of the syndesmosis joint and less long-term residual pain.

Level of evidence

II.

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References

  1. Alsousou J, Thompson M, Hulley P, Noble A, Willett K (2009) The biology of platelet-rich plasma and its application in trauma and orthopaedic surgery: a review of the literature. J Bone Joint Surg Br 91(8):987–996

    Article  CAS  PubMed  Google Scholar 

  2. Anitua E, Andia I, Sanchez M, Azofra J, del Mar Zalduendo M, de la Fuente M, Nurden P, Nurden AT (2005) Autologous preparations rich in growth factors promote proliferation and induce VEGF and HGF production by human tendon cells in culture. J Orthop Res 23(2):281–286

    Article  CAS  PubMed  Google Scholar 

  3. Anitua E, Sanchez M, Nurden AT, Nurden P, Orive G, Andia I (2006) New insights into and novel applications for platelet-rich fibrin therapies. Trends Biotechnol 24(5):227–234

    Article  CAS  PubMed  Google Scholar 

  4. Anitua E, Sanchez M, Nurden AT, Zalduendo M, de la Fuente M, Azofra J, Andia I (2007) Reciprocal actions of platelet-secreted TGF-beta1 on the production of VEGF and HGF by human tendon cells. Plast Reconstr Surg 119(3):950–959

    Article  CAS  PubMed  Google Scholar 

  5. Anitua E, Sanchez M, Orive G, Andia I (2007) The potential impact of the preparation rich in growth factors (PRGF) in different medical fields. Biomaterials 28(31):4551–4560

    Article  CAS  PubMed  Google Scholar 

  6. Anitua E, Sanchez M, Orive G, Andia I (2008) Delivering growth factors for therapeutics. Trends Pharmacol Sci 29(1):37–41

    Article  CAS  PubMed  Google Scholar 

  7. Bartonicek J (2003) Anatomy of the tibiofibular syndesmosis and its clinical relevance. Surg Radiol Anat 25(5–6):379–386

    Article  PubMed  Google Scholar 

  8. Boytim MJ, Fischer DA, Neumann L (1991) Syndesmotic ankle sprains. Am J Sports Med 19(3):294–298

    Article  CAS  PubMed  Google Scholar 

  9. Bubnov R, Yevseenko V, Semeniv I (2013) Ultrasound guided injections of platelets rich plasma for muscle injury in professional athletes. Comparative study. Med Ultrason 15(2):101–105

    Article  PubMed  Google Scholar 

  10. Close JR (1956) Some applications of the functional anatomy of the ankle joint. J Bone Joint Surg Am 38(4):761–781

    PubMed  Google Scholar 

  11. Dattani R, Patnaik S, Kantak A, Srikanth B, Selvan TP (2008) Injuries to the tibiofibular syndesmosis. J Bone Joint Surg Br 90(4):405–410

    Article  CAS  PubMed  Google Scholar 

  12. Delee JC, Drez DJ (2002) Orthopaedic sports medicine: principles and practice, vol 2. Saunders, Philadelphia

    Google Scholar 

  13. Dohan Ehrenfest DM, Rasmusson L, Albrektsson T (2009) Classification of platelet concentrates: from pure platelet-rich plasma (P-PRP) to leucocyte- and platelet-rich fibrin (L-PRF). Trends Biotechnol 27(3):158–167

    Article  CAS  PubMed  Google Scholar 

  14. Ebraheim NA, Lu J, Yang H, Mekhail AO, Yeasting RA (1997) Radiographic and CT evaluation of tibiofibular syndesmotic diastasis: a cadaver study. Foot Ankle Int 18(11):693–698

    Article  CAS  PubMed  Google Scholar 

  15. Ebraheim NA, Taser F, Shafiq Q, Yeasting RA (2006) Anatomical evaluation and clinical importance of the tibiofibular syndesmosis ligaments. Surg Radiol Anat 28(2):142–149

    Article  PubMed  Google Scholar 

  16. Edwards GS Jr, DeLee JC (1984) Ankle diastasis without fracture. Foot Ankle 4(6):305–312

    Article  PubMed  Google Scholar 

  17. Eppley BL, Woodell JE, Higgins J (2004) Platelet quantification and growth factor analysis from platelet-rich plasma: implications for wound healing. Plast Reconstr Surg 114(6):1502–1508

    Article  PubMed  Google Scholar 

  18. Fernández-Sarmiento JA, Domínguez JM, Granados MM, Morgaz J, Navarrete R, Carrillo JM, Gómez-Villamandos RJ, Muñoz-Rascón P, Martín de Las Mulas J, Millán Y, García-Balletbó M, Cugat R (2013) Histological study of the influence of plasma rich in growth factors (PRGF) on the healing of divided Achilles tendons in sheep. J Bone Joint Surg Am 95(3):246–255

    Article  PubMed  Google Scholar 

  19. Filardo G, Kon E, Della Villa S, Vincentelli F, Fornasari PM, Marcacci M (2010) Use of platelet-rich plasma for the treatment of refractory jumper’s knee. Int Orthop 34(6):909–915

    Article  PubMed Central  PubMed  Google Scholar 

  20. Graziani F, Ivanovski S, Cei S, Ducci F, Tonetti M, Gabriele M (2006) The in vitro effect of different PRP concentrations on osteoblasts and fibroblasts. Clin Oral Implants Res 17(2):212–219

    Article  PubMed  Google Scholar 

  21. Hall MP, Band PA, Meislin RJ, Jazrawi LM, Cardone DA (2009) Platelet-rich plasma: current concepts and application in sports medicine. J Am Acad Orthop Surg 17(10):602–608

    PubMed  Google Scholar 

  22. Hammond JW, Hinton RY, Curl LA, Muriel JM, Lovering RM (2009) Use of autologous platelet-rich plasma to treat muscle strain injuries. Am J Sports Med 37(6):1135–1142

    Article  PubMed Central  PubMed  Google Scholar 

  23. Hopkinson WJ, Pierre PS, Ryan JB, Wheeler JH (1990) Syndesmosis sprains of the ankle. Foot Ankle 10(6):325–330

    Article  CAS  PubMed  Google Scholar 

  24. Hunt KJ, George E, Harris AH, Dragoo JL (2013) Epidemiology of syndesmosis injuries in intercollegiate football: incidence and risk factors from National Collegiate Athletic Association injury surveillance system data from 2004–2005 to 2008–2009. Clin J Sport Med 23(4):278–282

    Article  PubMed  Google Scholar 

  25. Jones MH, Amendola A (2007) Syndesmosis sprains of the ankle: a systematic review. Clin Orthop Relat Res 455:173–175

    Article  PubMed  Google Scholar 

  26. Kajikawa Y, Morihara T, Sakamoto H, Matsuda K, Oshima Y, Yoshida A, Nagae M, Arai Y, Kawata M, Kubo T (2008) Platelet-rich plasma enhances the initial mobilization of circulation-derived cells for tendon healing. J Cell Physiol 215(3):837–845

    Article  CAS  PubMed  Google Scholar 

  27. Katznelson A, Lin E, Militiano J (1983) Ruptures of the ligaments about the tibio-fibular syndesmosis. Injury 15(3):170–172

    Article  CAS  PubMed  Google Scholar 

  28. Lin CF, Gross ML, Weinhold P (2006) Ankle syndesmosis injuries: anatomy, biomechanics, mechanism of injury, and clinical guidelines for diagnosis and intervention. J Orthop Sports Phys Ther 36(6):372–384

    Article  PubMed  Google Scholar 

  29. Mei-Dan O, Carmont M, Kots E, Barchilon V, Nyska M, Mann G (2010) Early return to play following complete rupture of the medial collateral ligament of the elbow using preparation rich in growth factors: a case report. J Shoulder Elbow Surg 19(5):e1–e5

    Article  PubMed  Google Scholar 

  30. Mei-Dan O, Carmont M, Laver L, Nyska M, Kammar H, Mann G, Clarck B, Kots E (2013) Standardization of the functional syndesmosis widening by dynamic US examination. BMC Sports Sci Med Rehabil 5:9

    Article  PubMed Central  PubMed  Google Scholar 

  31. Mei-Dan O, Kots E, Barchilon V, Massarwe S, Nyska M, Mann G (2009) A dynamic ultrasound examination for the diagnosis of ankle syndesmotic injury in professional athletes: a preliminary study. Am J Sports Med 37(5):1009–1016

    Article  PubMed  Google Scholar 

  32. Mei-Dan O, Lippi G, Sanchez M, Andia I, Maffulli N (2010) Autologous platelet-rich plasma: a revolution in soft tissue sports injury management? Phys Sportsmed 38(4):127–135

    Article  PubMed  Google Scholar 

  33. Mei-Dan O, Mann G, Maffulli N (2010) Platelet-rich plasma: any substance into it? Br J Sports Med 44(9):618–619

    Article  CAS  PubMed  Google Scholar 

  34. Menetrey J, Kasemkijwattana C, Day CS, Bosch P, Vogt M, Fu FH, Moreland MS, Huard J (2000) Growth factors improve muscle healing in vivo. J Bone Joint Surg Br 82(1):131–137

    Article  CAS  PubMed  Google Scholar 

  35. Milz P, Milz S, Steinborn M, Mittlmeier T, Putz R, Reiser M (1998) Lateral ankle ligaments and tibiofibular syndesmosis. 13-MHz high-frequency sonography and MRI compared in 20 patients. Acta Orthop Scand 69(1):51–55

    Article  CAS  PubMed  Google Scholar 

  36. Mishra A, Woodall J Jr, Vieira A (2009) Treatment of tendon and muscle using platelet-rich plasma. Clin Sports Med 28(1):113–125

    Article  PubMed  Google Scholar 

  37. Muhle C, Frank LR, Rand T, Ahn JM, Yeh LR, Trudell D, Haghighi P, Resnick D (1998) Tibiofibular syndesmosis: high-resolution MRI using a local gradient coil. J Comput Assist Tomogr 22(6):938–944

    Article  CAS  PubMed  Google Scholar 

  38. Murray MM, Bennett R, Zhang X, Spector M (2002) Cell outgrowth from the human ACL in vitro: regional variation and response to TGF-beta1. J Orthop Res 20(4):875–880

    Article  CAS  PubMed  Google Scholar 

  39. Nielson JH, Gardner MJ, Peterson MG, Sallis JG, Potter HG, Helfet DL, Lorich DG (2005) Radiographic measurements do not predict syndesmotic injury in ankle fractures: an MRI study. Clin Orthop Relat Res 436:216–221

    Article  PubMed  Google Scholar 

  40. Norkus SA, Floyd RT (2001) The anatomy and mechanisms of syndesmotic ankle sprains. J Athl Train 36(1):68–73

    PubMed Central  CAS  PubMed  Google Scholar 

  41. Nussbaum ED, Hosea TM, Sieler SD, Incremona BR, Kessler DE (2001) Prospective evaluation of syndesmotic ankle sprains without diastasis. Am J Sports Med 29(1):31–35

    CAS  PubMed  Google Scholar 

  42. Peerbooms JC, Sluimer J, Bruijn DJ, Gosens T (2010) Positive effect of an autologous platelet concentrate in lateral epicondylitis in a double-blind randomized controlled trial: platelet-rich plasma versus corticosteroid injection with a 1-year follow-up. Am J Sports Med 38(2):255–262

    Article  PubMed  Google Scholar 

  43. Sampson S, Gerhardt M, Mandelbaum B (2008) Platelet rich plasma injection grafts for musculoskeletal injuries: a review. Curr Rev Musculoskelet Med 1(3–4):165–174

    Article  PubMed Central  PubMed  Google Scholar 

  44. Sanchez M, Anitua E, Azofra J (2009) Local injections of endogenous growth factors for Achilles tendon pathology. Monographic series of surgical techniques in orthopaedics and traumatology. In: Mafulli N, Oliva F (eds) Achilles tendon. CIC Edizione Internazionali, Rome, pp 92–100

    Google Scholar 

  45. Sanchez M, Anitua E, Azofra J, Aguirre JJ, Andia I (2008) Intra-articular injection of an autologous preparation rich in growth factors for the treatment of knee OA: a retrospective cohort study. Clin Exp Rheumatol 26(5):910–913

    CAS  PubMed  Google Scholar 

  46. Sanchez M, Anitua E, Azofra J, Andia I, Padilla S, Mujika I (2007) Comparison of surgically repaired Achilles tendon tears using platelet-rich fibrin matrices. Am J Sports Med 35(2):245–251

    Article  PubMed  Google Scholar 

  47. Sanchez M, Anitua E, Orive G, Mujika I, Andia I (2009) Platelet-rich therapies in the treatment of orthopaedic sport injuries. Sports Med 39(5):345–354

    Article  PubMed  Google Scholar 

  48. Sarrafian SK (1993) Anatomy of the foot and ankle: descriptive, topographic, Functional. JB Lippincott, Philadelphia

    Google Scholar 

  49. Serpell BG, Ford M, Young WB (2010) The development of a new test of agility for rugby league. J Strength Cond Res 24(12):3270–3277

    Article  PubMed  Google Scholar 

  50. Takao M, Ochi M, Oae K, Naito K, Uchio Y (2003) Diagnosis of a tear of the tibiofibular syndesmosis. The role of arthroscopy of the ankle. J Bone Joint Surg Br 85(3):324–329

    Article  CAS  PubMed  Google Scholar 

  51. Taser F, Shafiq Q, Ebraheim NA (2006) Three-dimensional volume rendering of tibiofibular joint space and quantitative analysis of change in volume due to tibiofibular syndesmosis diastases. Skelet Radiol 35(12):935–941

    Article  CAS  Google Scholar 

  52. Taylor DC, Tenuta JJ, Uhorchak JM, Arciero RA (2007) Aggressive surgical treatment and early return to sports in athletes with grade III syndesmosis sprains. Am J Sports Med 35(11):1833–1838

    Article  PubMed  Google Scholar 

  53. Vogl TJ, Hochmuth K, Diebold T, Lubrich J, Hofmann R, Stockle U, Sollner O, Bisson S, Sudkamp N, Maeurer J, Haas N, Felix R (1997) Magnetic resonance imaging in the diagnosis of acute injured distal tibiofibular syndesmosis. Invest Radiol 32(7):401–409

    Article  CAS  PubMed  Google Scholar 

  54. Weiler A, Forster C, Hunt P, Falk R, Jung T, Unterhauser FN, Bergmann V, Schmidmaier G, Haas NP (2004) The influence of locally applied platelet-derived growth factor-BB on free tendon graft remodeling after anterior cruciate ligament reconstruction. Am J Sports Med 32(4):881–891

    Article  PubMed  Google Scholar 

  55. Wetzel RJ, Patel RM, Terry MA (2013) Platelet-rich plasma as an effective treatment for proximal hamstring injuries. Orthopedics 36(1):e64–e70

    Article  PubMed  Google Scholar 

  56. Wright RW, Barile RJ, Surprenant DA, Matava MJ (2004) Ankle syndesmosis sprains in national hockey league players. Am J Sports Med 32(8):1941–1945

    Article  PubMed  Google Scholar 

  57. Yamazaki S, Yasuda K, Tomita F, Tohyama H, Minami A (2005) The effect of transforming growth factor-beta1 on intraosseous healing of flexor tendon autograft replacement of anterior cruciate ligament in dogs. Arthroscopy 21(9):1034–1041

    Article  PubMed  Google Scholar 

  58. Yoshikawa T, Tohyama H, Enomoto H, Matsumoto H, Toyama Y, Yasuda K (2006) Expression of vascular endothelial growth factor and angiogenesis in patellar tendon grafts in the early phase after anterior cruciate ligament reconstruction. Knee Surg Sports Traumatol Arthrosc 14(9):804–810

    Article  CAS  PubMed  Google Scholar 

  59. Yoshioka T, Kanamori A, Washio T, Aoto K, Uemura K, Sakane M, Ochiai N (2013) The effects of plasma rich in growth factors (PRGF-Endoret) on healing of medial collateral ligament of the knee. Knee Surg Sports Traumatol Arthrosc 21(8):1763–1769

    Article  PubMed  Google Scholar 

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Correspondence to Lior Laver.

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Laver, L., Carmont, M.R., McConkey, M.O. et al. Plasma rich in growth factors (PRGF) as a treatment for high ankle sprain in elite athletes: a randomized control trial. Knee Surg Sports Traumatol Arthrosc 23, 3383–3392 (2015). https://doi.org/10.1007/s00167-014-3119-x

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