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MUSCULOSKELETAL SURGERY

, Volume 99, Issue 3, pp 243–248 | Cite as

Role of autologous platelet-rich plasma in treatment of long-bone nonunions: a prospective study

  • R. Malhotra
  • V. Kumar
  • B. GargEmail author
  • R. Singh
  • V. Jain
  • P. Coshic
  • K. Chatterjee
Original Article

Abstract

Purpose

Fracture union is a complex biological process, which depends upon several systemic and local factors. Disturbance of any of these factors may lead to nonunion of the fracture. These nonunions have a huge impact on quality of life as well as socioeconomical aspects. The platelets on activation release a number of growth factors and differentiation factors, which play important role in fracture healing. This study aimed to look for efficacy of platelet-rich plasma in the treatment of established fracture nonunions of long bones.

Methods

A total of 94 patients with established nonunion of long bone (35 tibia, 30 femur, 11 humerus, 4 radius, 12 ulna, 2 with both radius and ulna) were included in this study. We injected 15–20 ml of autologous platelet-rich plasma (>2,000,000 platelets/μl) under image intensifier at each nonunion site. The fracture union was evaluated clinically and radiologically regularly at monthly interval till 4 months.

Results

Eighty-two patients had their fracture united at the end of 4 months. Thirty-four patients showed bridging trabeculae on X-rays at the end of 2 months, while 41 patients showed bridging trabeculae at the end of third month. Twelve patients did not show any attempt of union at 4 months and were labeled as failure of treatment. There were no complications.

Conclusion

Platelet-rich plasma is a safe and effective treatment for the treatment of nonunions. More studies are needed to look into molecular mechanism of this fracture healing acceleration by platelet-rich plasma.

Keywords

Nonunion Platelet-rich plasma (PRP) Femur Tibia Humerus Radius 

Notes

Acknowledgments

We would like to thank Indian Council of Medical Research (ICMR) for funding this study.

Compliance with ethical standards

Conflict of interest

None.

References

  1. 1.
    Bauer TW, Muschler GF (2000) Bone graft materials. An overview of the basic science. Clin Orthop Relat Res 371:10–27CrossRefPubMedGoogle Scholar
  2. 2.
    Fleming JE Jr, Cornell CN, Muschler GF (2000) Bone cells and matrices in orthopedic tissue engineering. Orthop Clin North Am 31(3):357–374CrossRefPubMedGoogle Scholar
  3. 3.
    Giannoudis PV, Dinopoulos H, Tsiridis E (2005) Bone substitutes: an update. Injury 36(Suppl 3):S20–S27CrossRefPubMedGoogle Scholar
  4. 4.
    Finkemeier CG (2002) Bone-grafting and bone-graft substitutes. J Bone Joint Surg Am 84-A(3):454–464PubMedGoogle Scholar
  5. 5.
    Saikia KC, Bhattacharya TD, Bhuyan SK, Talukdar DJ, Saikia SP, Jitesh P (2008) Calcium phosphate ceramics as bone graft substitutes in filling bone tumor defects. Indian J Orthop 42(2):169–172PubMedCentralCrossRefPubMedGoogle Scholar
  6. 6.
    Younger EM, Chapman MW (1989) Morbidity at bone graft donor sites. J Orthop Trauma 3(3):192–195CrossRefPubMedGoogle Scholar
  7. 7.
    Sánchez AR, Sheridan PJ, Kupp LI (2003) Is platelet-rich plasma the perfect enhancement factor? A current review. Int J Oral Maxillofac Implants 18(1):93–103PubMedGoogle Scholar
  8. 8.
    Marx RE, Carlson ER, Eichstaedt RM, Schimmele SR, Strauss JE, Georgeff KR (1998) Platelet-rich plasma: growth factor enhancement for bone grafts. Oral Surg Oral Med Oral Pathol Oral Radiol Endodontol 85(6):638–646CrossRefGoogle Scholar
  9. 9.
    Harrison P, Cramer EM (1993) Platelet alpha-granules. Blood Rev 7(1):52–62CrossRefPubMedGoogle Scholar
  10. 10.
    Bucholz RW, Einhorn TA, Marsh JL (2006) Bone and joint healing. In: Bucholz RW, Heck-man JD, Court-Brown C (eds) Rockwood & Green’s fractures in adults, 6th edn. Lippincott Williams & Wilkins, Philadelphia, pp 300–311Google Scholar
  11. 11.
    Schilephake H (2002) Bone growth factors in maxillofacial skeletal reconstruction. Int J Oral Maxillofac Surg 31(5):469–484CrossRefPubMedGoogle Scholar
  12. 12.
    Mehta S, Watson JT (2008) Platelet rich concentrate: basic science and current clinical applications. J Orthop Trauma 22(6):432–438CrossRefPubMedGoogle Scholar
  13. 13.
    Gandhi A, Doumas C, Dumas C, O’Connor JP, Parsons JR, Lin SS (2006) The effects of local platelet rich plasma delivery on diabetic fracture healing. Bone 38(4):540–546CrossRefPubMedGoogle Scholar
  14. 14.
    Wilkins RM, Chimenti BT, Rifkin RM (2003) Percutaneous treatment of long bone nonunions: the use of autologous bone marrow and allograft bone matrix. Orthopedics 26(5 Suppl):s549–s554PubMedGoogle Scholar
  15. 15.
    Heckman JD, Ryaby JP, McCabe J, Frey JJ, Kilcoyne RF (1994) Acceleration of tibial fracture-healing by non-invasive, low-intensity pulsed ultrasound. J Bone Joint Surg Am 76(1):26–34PubMedGoogle Scholar
  16. 16.
    Corrales LA, Morshed S, Bhandari M, Miclau T 3rd (2008) Variability in the assessment of fracture-healing in orthopaedic trauma studies. J Bone Joint Surg Am 90(9):1862–1868PubMedCentralCrossRefPubMedGoogle Scholar
  17. 17.
    Wilkins RM, Kelly CM (2003) The effect of allomatrix injectable putty on the outcome of long bone applications. Orthopedics 26(5 Suppl):s567–s570PubMedGoogle Scholar
  18. 18.
    Simpson AHRW, Mills L, Noble B (2006) The role of growth factors and related agents in accelerating fracture healing. J Bone Joint Surg Br 88(6):701–705CrossRefPubMedGoogle Scholar
  19. 19.
    Dimitriou R, Dahabreh Z, Katsoulis E, Matthews SJ, Branfoot T, Giannoudis PV (2005) Application of recombinant BMP-7 on persistent upper and lower limb non-unions. Injury 36(Suppl 4):S51–S59CrossRefPubMedGoogle Scholar
  20. 20.
    Friedlaender GE, Perry CR, Cole JD, Cook SD, Cierny G, Muschler GF et al (2001) Osteogenic protein-1 (bone morphogenetic protein-7) in the treatment of tibial nonunions. J Bone Joint Surg Am 83-A(Suppl 1(Pt 2)):S151–S158PubMedGoogle Scholar
  21. 21.
    Goel A, Sangwan SS, Siwach RC, Ali AM (2005) Percutaneous bone marrow grafting for the treatment of tibial non-union. Injury 36(1):203–206CrossRefPubMedGoogle Scholar
  22. 22.
    Connolly JF (1995) Injectable bone marrow preparations to stimulate osteogenic repair. Clin Orthop Relat Res 313:8–18PubMedGoogle Scholar
  23. 23.
    Healey JH, Zimmerman PA, McDonnell JM, Lane JM (1990) Percutaneous bone marrow grafting of delayed union and nonunion in cancer patients. Clin Orthop Relat Res 256:280–285PubMedGoogle Scholar
  24. 24.
    Hernigou P, Poignard A, Beaujean F, Rouard H (2005) Percutaneous autologous bone-marrow grafting for nonunions. Influence of the number and concentration of progenitor cells. J Bone Joint Surg Am 87(7):1430–1437CrossRefPubMedGoogle Scholar
  25. 25.
    Mishra A, Pavelko T (2006) Treatment of chronic elbow tendinosis with buffered platelet-rich plasma. Am J Sports Med 34(11):1774–1778CrossRefPubMedGoogle Scholar
  26. 26.
    Bielecki TM, Gazdzik TS (2006) Percutaneous injection of autogenous growth factors in patient with nonunion of the humerus. A case report. J Orthop 3(3):15Google Scholar
  27. 27.
    Calori GM, D’Avino M, Tagliabue L, Albisetti W, d’ Imporzano M, Peretti G (2006) An ongoing research for evaluation of treatment with BMPs or AGFs in long bone non-union: protocol description and preliminary results. Injury 37(Suppl 3):S43–S50CrossRefPubMedGoogle Scholar
  28. 28.
    Fréchette J-P, Martineau I, Gagnon G (2005) Platelet-rich plasmas: growth factor content and roles in wound healing. J Dent Res 84(5):434–439CrossRefPubMedGoogle Scholar
  29. 29.
    George JN (2000) Platelets. Lancet 355(9214):1531–1539CrossRefPubMedGoogle Scholar
  30. 30.
    Slater M, Patava J, Kingham K, Mason RS (1995) Involvement of platelets in stimulating osteogenic activity. J Orthop Res 13(5):655–663CrossRefPubMedGoogle Scholar
  31. 31.
    Dallari D, Fini M, Stagni C, Torricelli P, Nicoli Aldini N, Giavaresi G et al (2006) In vivo study on the healing of bone defects treated with bone marrow stromal cells, platelet-rich plasma, and freeze-dried bone allografts, alone and in combination. J Orthop Res 24(5):877–888CrossRefPubMedGoogle Scholar
  32. 32.
    Lind M (1998) Growth factor stimulation of bone healing. Effects on osteoblasts, osteomies, and implants fixation. Acta Orthop Scand Suppl 283:2–37PubMedGoogle Scholar
  33. 33.
    Beck LS, Amento EP, Xu Y, Deguzman L, Lee WP, Nguyen T et al (1993) TGF-beta 1 induces bone closure of skull defects: temporal dynamics of bone formation in defects exposed to rhTGF-beta 1. J Bone Miner Res 8(6):753–761CrossRefPubMedGoogle Scholar
  34. 34.
    Nielsen HM, Andreassen TT, Ledet T, Oxlund H (1994) Local injection of TGF-beta increases the strength of tibial fractures in the rat. Acta Orthop Scand 65(1):37–41CrossRefPubMedGoogle Scholar
  35. 35.
    Whitman DH, Berry RL, Green DM (1997) Platelet gel: an autologous alternative to fibrin glue with applications in oral and maxillofacial surgery. J Oral Maxillofac Surg 55(11):1294–1299CrossRefPubMedGoogle Scholar
  36. 36.
    Anitua E (1999) Plasma rich in growth factors: preliminary results of use in the preparation of future sites for implants. Int J Oral Maxillofac Implants 14(4):529–535PubMedGoogle Scholar
  37. 37.
    Lowery GL, Kulkarni S, Pennisi AE (1999) Use of autologous growth factors in lumbar spinal fusion. Bone 25(2 Suppl):47S–50SCrossRefPubMedGoogle Scholar
  38. 38.
    Parsons P, Butcher A, Hesselden K, Ellis K, Maughan J, Milner R et al (2008) Platelet-rich concentrate supports human mesenchymal stem cell proliferation, bone morphogenetic protein-2 messenger RNA expression, alkaline phosphatase activity, and bone formation in vitro: a mode of action to enhance bone repair. J Orthop Trauma 22(9):595–604CrossRefPubMedGoogle Scholar
  39. 39.
    Gandhi A, Bibbo C, Pinzur M, Lin SS (2005) The role of platelet-rich plasma in foot and ankle surgery. Foot Ankle Clin 10(4):621–637CrossRefPubMedGoogle Scholar
  40. 40.
    Bielecki T, Gazdzik TS, Szczepanski T (2008) Benefit of percutaneous injection of autologous platelet-leukocyte-rich gel in patients with delayed union and nonunion. Eur Surg Res 40(3):289–296CrossRefPubMedGoogle Scholar
  41. 41.
    Ogino Y, Ayukawa Y, Kukita T, Koyano K (2006) The contribution of platelet-derived growth factor, transforming growth factor-beta1, and insulin-like growth factor-I in platelet-rich plasma to the proliferation of osteoblast-like cells. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 101(6):724–729CrossRefPubMedGoogle Scholar
  42. 42.
    Bielecki T, Gazdzik TS, Szczepanski T (2006) Re: “The effects of local platelet rich plasma delivery on diabetic fracture healing”. What do we use: platelet-rich plasma or platelet-rich gel? Bone 39(6):1388; author reply 1389 Google Scholar
  43. 43.
    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):987–996CrossRefPubMedGoogle Scholar
  44. 44.
    Lomax C, Traub O (2009) Topical thrombins: benefits and risks. Pharmacotherapy 29(7 Pt 2):8S–12SCrossRefPubMedGoogle Scholar
  45. 45.
    Di Matteo B, Filardo G, Kon E, Marcacci M (2015) Platelet-rich plasma: evidence for the treatment of patellar and Achilles tendinopathy—a systematic review. Musculoskelet Surg 99(1):1–9CrossRefPubMedGoogle Scholar
  46. 46.
    Turajane T, Thitiset T, Honsawek S, Chaveewanakorn U, Aojanepong J, Papadopoulos KI (2014) Assessment of chondrogenic differentiation potential of autologous activated peripheral blood stem cells on human early osteoarthritic cancellous tibial bone scaffold. Musculoskelet Surg 98(1):35–43CrossRefPubMedGoogle Scholar
  47. 47.
    Gonshor A (2002) Technique for producing platelet-rich plasma and platelet concentrate: background and process. Int J Periodontics Restor Dent 22(6):547–557Google Scholar
  48. 48.
    Say F, Türkeli E, Bülbül M (2014) Is platelet-rich plasma injection an effective choice in cases of non-union? Acta Chir Orthop Traumatol Cech 81(5):340–345PubMedGoogle Scholar

Copyright information

© Istituto Ortopedico Rizzoli 2015

Authors and Affiliations

  • R. Malhotra
    • 1
  • V. Kumar
    • 1
  • B. Garg
    • 1
    Email author
  • R. Singh
    • 1
  • V. Jain
    • 1
  • P. Coshic
    • 2
  • K. Chatterjee
    • 2
  1. 1.Department of OrthopedicsAll India Institute of Medical SciencesNew DelhiIndia
  2. 2.Department of Transfusion MedicineAIIMSNew DelhiIndia

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