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.
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References
Bauer TW, Muschler GF (2000) Bone graft materials. An overview of the basic science. Clin Orthop Relat Res 371:10–27
Fleming JE Jr, Cornell CN, Muschler GF (2000) Bone cells and matrices in orthopedic tissue engineering. Orthop Clin North Am 31(3):357–374
Giannoudis PV, Dinopoulos H, Tsiridis E (2005) Bone substitutes: an update. Injury 36(Suppl 3):S20–S27
Finkemeier CG (2002) Bone-grafting and bone-graft substitutes. J Bone Joint Surg Am 84-A(3):454–464
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):169–172
Younger EM, Chapman MW (1989) Morbidity at bone graft donor sites. J Orthop Trauma 3(3):192–195
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):93–103
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):638–646
Harrison P, Cramer EM (1993) Platelet alpha-granules. Blood Rev 7(1):52–62
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 300–311
Schilephake H (2002) Bone growth factors in maxillofacial skeletal reconstruction. Int J Oral Maxillofac Surg 31(5):469–484
Mehta S, Watson JT (2008) Platelet rich concentrate: basic science and current clinical applications. J Orthop Trauma 22(6):432–438
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):540–546
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–s554
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):26–34
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):1862–1868
Wilkins RM, Kelly CM (2003) The effect of allomatrix injectable putty on the outcome of long bone applications. Orthopedics 26(5 Suppl):s567–s570
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):701–705
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–S59
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–S158
Goel A, Sangwan SS, Siwach RC, Ali AM (2005) Percutaneous bone marrow grafting for the treatment of tibial non-union. Injury 36(1):203–206
Connolly JF (1995) Injectable bone marrow preparations to stimulate osteogenic repair. Clin Orthop Relat Res 313:8–18
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 256:280–285
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):1430–1437
Mishra A, Pavelko T (2006) Treatment of chronic elbow tendinosis with buffered platelet-rich plasma. Am J Sports Med 34(11):1774–1778
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):15
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–S50
Fréchette J-P, Martineau I, Gagnon G (2005) Platelet-rich plasmas: growth factor content and roles in wound healing. J Dent Res 84(5):434–439
George JN (2000) Platelets. Lancet 355(9214):1531–1539
Slater M, Patava J, Kingham K, Mason RS (1995) Involvement of platelets in stimulating osteogenic activity. J Orthop Res 13(5):655–663
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):877–888
Lind M (1998) Growth factor stimulation of bone healing. Effects on osteoblasts, osteomies, and implants fixation. Acta Orthop Scand Suppl 283:2–37
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):753–761
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):37–41
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):1294–1299
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):529–535
Lowery GL, Kulkarni S, Pennisi AE (1999) Use of autologous growth factors in lumbar spinal fusion. Bone 25(2 Suppl):47S–50S
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):595–604
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):621–637
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):289–296
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):724–729
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
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
Lomax C, Traub O (2009) Topical thrombins: benefits and risks. Pharmacotherapy 29(7 Pt 2):8S–12S
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):1–9
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):35–43
Gonshor A (2002) Technique for producing platelet-rich plasma and platelet concentrate: background and process. Int J Periodontics Restor Dent 22(6):547–557
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):340–345
Acknowledgments
We would like to thank Indian Council of Medical Research (ICMR) for funding this study.
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Malhotra, R., Kumar, V., Garg, B. et al. Role of autologous platelet-rich plasma in treatment of long-bone nonunions: a prospective study. Musculoskelet Surg 99, 243–248 (2015). https://doi.org/10.1007/s12306-015-0378-8
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DOI: https://doi.org/10.1007/s12306-015-0378-8