Effectiveness of percutaneous injection of autologous concentrated bone marrow aspirate combined with platelet-rich plasma in treatment of delayed fracture healing_Chinese Journal of Reparative and Reconstructive Surgery

Authors：

TANG Yanfeng , YANG Yuxia , LI Hongjun , XI Jianing , LI Wuyin , YUE Chen , WANG Huichao ,  LIU Youwen

Hip Injury Center, Luoyang-Orthopedic Traumatological Hospital of Henan Province (Henan Orthopedic Hospital), Luoyang Henan, 471002, P.R.China;

Corresponding author：

LIU Youwen, Email: liuyouwen534@sina.com

Keywords：

Delayed fracture healing; concentrated bone marrow aspirate; platelet-rich plasma; minimally invasive therapy

DOI：

10.7507/1002-1892.202002028

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Objective To analyze the effectiveness of percutaneous injection of autologous concentrated bone marrow aspirate (cBMA) combined with platelet-rich plasma (PRP) in the treatment of delayed fracture healing.Methods A prospective, randomized, controlled, single-blind case study was conducted. Between March 2016 and July 2018, 66 patients who met the inclusion and exclusion criteria for delayed fracture healing but had solid internal fixation of the fracture end were randomly divided into control group (31 cases, treated with percutaneous autogenous bone marrow blood injection) and study group (35 cases, treated with percutaneous autogenous cBMA+PRP injection). General data such as gender, age, body mass index, site of delayed fracture healing, length of bone defect at fracture end, and preoperative radiographic union score for tibia (RUST) showed no significant difference between the two groups (P>0.05). Before injection, Kirschner wire was used in both groups to stimulate the fracture end and cause minor injury. The fracture healing time, treatment cost, and adverse reactions were recorded and compared between the two groups. Visual analogue scale (VAS) score was used to evaluate pain improvement. The tibial RUST score was extended to the tubular bone healing evaluation.Results No infection of bone marrow puncture needle eyes occurred in both groups. In the control group, local swelling was obvious in 5 cases and pain was aggravated at 1 day after operation in 11 cases. In the study group, postoperative swelling and pain were not obvious, but 2 cases presented local swelling and pain. All of them relieved after symptomatic treatment. Patients in both groups were followed up, the follow-up time of the control group was 16-36 months (mean, 21.8 months), and the study group lasted 14-33 months (mean, 23.2 months). The amount of bone marrow blood was significantly lower in the study group than in the control group (t=4.610, P=0.000). The degree of postoperative pain in the study group was less than that in the control group, and the treatment cost was higher than that in the control group. But the differences between the two groups in VAS score at 1 day after operation and treatment cost were not significant (P>0.05). Fracture healing was achieved in 19 cases (61.3%) in the control group and 30 cases (85.7%) in the study group. The difference in fracture healing rate between the two groups was significant (χ²=5.128, P=0.024). Fracture healing time and RUST score at last follow-up were significantly better in the study group than in the control group (P<0.05). At last follow-up, RUST scores in both groups were significantly improved when compared with those before operation (P<0.05).Conclusion Autogenous cBMA combined with PRP percutaneous injection can provide high concentration of BMSCs and growth factors, and can improve the fracture healing rate and shorten the fracture healing time better than autogenous bone marrow blood injection.

Citation： TANG Yanfeng, YANG Yuxia, LI Hongjun, XI Jianing, LI Wuyin, YUE Chen, WANG Huichao, LIU Youwen. Effectiveness of percutaneous injection of autologous concentrated bone marrow aspirate combined with platelet-rich plasma in treatment of delayed fracture healing. Chinese Journal of Reparative and Reconstructive Surgery, 2020, 34(9): 1130-1135. doi: 10.7507/1002-1892.202002028 Copy

1.	Schlundt C, Bucher CH, Tsitsilonis S, et al. Clinical and research approaches to treat non-union fracture. Curr Osteoporos Rep, 2018, 16(2): 155-168.
2.	蔡鸿敏, 倘艳锋, 李红军, 等. 保留髂脊的髂骨翼取骨术. 中华骨科杂志, 2019, 39(10): 589-595.
3.	Wang W, Yeung KWK. Bone grafts and biomaterials substitutes for bone defect repair: A review. Bioact Mater, 2017, 2(4): 224-247.
4.	Connolly JF, Shindell R. Percutaneous marrow injection for an ununited tibia. Nebr Med J, 1986, 71(4): 105-107.
5.	Hernigou P, Poignard A, Manicom O, et al. The use of percutaneous autologous bone marrow transplantation in nonunion and avascular necrosis of bone. J Bone Joint Surg (Br), 2005, 87(7): 896-902.
6.	倘艳锋, 李启义, 刘又文, 等. 富血小板血浆促进骨修复的研究和应用进展. 中医正骨杂志, 2015, 27(4): 70-71.
7.	Roukoz S, El Khoury G, Saghbini E, et al. Does the induced membrane have antibacterial properties? An experimental rat model of a chronic infected nonunion Int Orthop, 2020, 44(2): 391-398.
8.	刘玉柯, 张敏, 李培玲, 等. ⁹⁹Tcm-MDP SPECT/CT 融合骨显像评价骨折远端愈合能力的应用价值. 国际放射医学核医学杂志, 2018, 42(3): 218-223.
9.	Whelan DB, Bhandari M, Stephen D, et al. Development of the radiographic union score for tibial fractures for the assessment of tibial fracture healing after intramedullary fixation. J Trauma, 2010, 68(3): 629-632.
10.	Field JR, Ruthenbeck GR. Qualitative and quantitative radiological measures of fracture healing. Vet Comp Orthop Traumatol, 2018, 31(1): 1-9.
11.	Xu B, Chen L, Lee JH. Smoking and alcohol drinking and risk of non-union or delayed union after fractures: A protocol for systematic review and dose-response meta-analysis. Medicine (Baltimore), 2020, 99(5): e18744.
12.	杨荣, 陈雁西. 四肢骨不连早期诊断的研究进展. 中华骨科杂志, 2018, 38(9): 563-569.
13.	Giannoudis PV, Gudipati S, Harwood P, et al. Long bone non-unions treated with the diamond concept: a case series of 64 patients. Injury, 2015, 46 Suppl 8: S48-S54.
14.	El-Jawhari JJ, Kleftouris G, El-Sherbiny Y, et al. Defective proliferation and osteogenic potential with altered immunoregulatory phenotype of native bone marrow-multipotential stromal cells in atrophic fracture non-union. Sci Rep, 2019, 9(1): 17340.
15.	Matsuda Y, Sakayama K, Okumura H, et al. Percutaneous autologous bone marrow transplantation for nonunion of the femur. Nihon Geka Hokan, 1998, 67(1): 10-17.
16.	Connolly JF. Injectable bone marrow preparations to stimulate osteogenic repair. Clin Orthop Relat Res, 1995, (313): 8-18.
17.	Garg NK, Gaur S, Sharma S. Percutaneous autogenous bone marrow grafting in 20 cases of ununited fracture. Acta Orthop Scand, 1993, 64(6): 671-672.
18.	Wu J, Guo H, Liu X, et al. Percutaneous autologous bone marrow transplantation for the treatment of delayed union of limb bone in children. Ther Clin Risk Manag, 2018, 14: 219-224.
19.	Braly HL, O’Connor DP, Brinker MR. Percutaneous autologous bone marrow injection in the treatment of distal meta-diaphyseal tibial nonunions and delayed unions. J Orthop Trauma, 2013, 27(9): 527-533.
20.	Gross JB, Diligent J, Bensoussan D, et al. Percutaneous autologous bone marrow injection for treatment of delayed and non-union of long bone: a retrospective study of 45 cases. Biomed Mater Eng, 2015, 25(1 Suppl): 187-197.
21.	Olivier M, Gay AM, Cerlier A, et al. Can we achieve bone healing using the diamong concept without bone grafting for recalcitrant tibial nonunions? Injury, 2015, 46(7): 1383-1388.
22.	Schäfer R, DeBaun MR, Fleck E, et al. Quantitation of progenitor cell populations and growth factors after bone marrow aspirate concentration. J Transl Med, 2019, 17(1): 115.
23.	Ling HS, Bolander J, Rustom LE, et al. Bone regeneration strategies: Engineered scaffolds, bioactive molecules and stem cells current stage and future perspectives. Biomaterials, 2018, 180: 143-162.
24.	王福科, 张红, 李彦林, 等. 联合培养血管内皮细胞与脂肪干细胞构建组织工程骨移位成骨. 中国修复重建外科杂志, 2019, 33(10): 1310-1319.
25.	伋琳, 宋辛维, 曾富海, 等. 生长因子控制释放对骨再生影响的研究进展. 中国修复重建外科杂志, 2019, 33(6): 750-755.
26.	倘艳锋, 李无阴, 李建明, 等. 自体生物活性浓集物局部注射治疗骨折延迟愈合的疗效分析. 中国现代医学杂志, 2015, 25(32): 105-108.
27.	倘艳锋, 杨玉霞, 李红军, 等. 经皮骨折断端骨皮质“刺削”并局部注射自体浓缩骨髓液和富血小板血浆混合物治疗骨折延迟愈合. 中华创伤骨科杂志, 2018, 20(11): 999-1003.

1. Schlundt C, Bucher CH, Tsitsilonis S, et al. Clinical and research approaches to treat non-union fracture. Curr Osteoporos Rep, 2018, 16(2): 155-168.
2. 蔡鸿敏, 倘艳锋, 李红军, 等. 保留髂脊的髂骨翼取骨术. 中华骨科杂志, 2019, 39(10): 589-595.
3. Wang W, Yeung KWK. Bone grafts and biomaterials substitutes for bone defect repair: A review. Bioact Mater, 2017, 2(4): 224-247.
4. Connolly JF, Shindell R. Percutaneous marrow injection for an ununited tibia. Nebr Med J, 1986, 71(4): 105-107.
5. Hernigou P, Poignard A, Manicom O, et al. The use of percutaneous autologous bone marrow transplantation in nonunion and avascular necrosis of bone. J Bone Joint Surg (Br), 2005, 87(7): 896-902.
6. 倘艳锋, 李启义, 刘又文, 等. 富血小板血浆促进骨修复的研究和应用进展. 中医正骨杂志, 2015, 27(4): 70-71.
7. Roukoz S, El Khoury G, Saghbini E, et al. Does the induced membrane have antibacterial properties? An experimental rat model of a chronic infected nonunion Int Orthop, 2020, 44(2): 391-398.
8. 刘玉柯, 张敏, 李培玲, 等. ⁹⁹Tcm-MDP SPECT/CT 融合骨显像评价骨折远端愈合能力的应用价值. 国际放射医学核医学杂志, 2018, 42(3): 218-223.
9. Whelan DB, Bhandari M, Stephen D, et al. Development of the radiographic union score for tibial fractures for the assessment of tibial fracture healing after intramedullary fixation. J Trauma, 2010, 68(3): 629-632.
10. Field JR, Ruthenbeck GR. Qualitative and quantitative radiological measures of fracture healing. Vet Comp Orthop Traumatol, 2018, 31(1): 1-9.
11. Xu B, Chen L, Lee JH. Smoking and alcohol drinking and risk of non-union or delayed union after fractures: A protocol for systematic review and dose-response meta-analysis. Medicine (Baltimore), 2020, 99(5): e18744.
12. 杨荣, 陈雁西. 四肢骨不连早期诊断的研究进展. 中华骨科杂志, 2018, 38(9): 563-569.
13. Giannoudis PV, Gudipati S, Harwood P, et al. Long bone non-unions treated with the diamond concept: a case series of 64 patients. Injury, 2015, 46 Suppl 8: S48-S54.
14. El-Jawhari JJ, Kleftouris G, El-Sherbiny Y, et al. Defective proliferation and osteogenic potential with altered immunoregulatory phenotype of native bone marrow-multipotential stromal cells in atrophic fracture non-union. Sci Rep, 2019, 9(1): 17340.
15. Matsuda Y, Sakayama K, Okumura H, et al. Percutaneous autologous bone marrow transplantation for nonunion of the femur. Nihon Geka Hokan, 1998, 67(1): 10-17.
16. Connolly JF. Injectable bone marrow preparations to stimulate osteogenic repair. Clin Orthop Relat Res, 1995, (313): 8-18.
17. Garg NK, Gaur S, Sharma S. Percutaneous autogenous bone marrow grafting in 20 cases of ununited fracture. Acta Orthop Scand, 1993, 64(6): 671-672.
18. Wu J, Guo H, Liu X, et al. Percutaneous autologous bone marrow transplantation for the treatment of delayed union of limb bone in children. Ther Clin Risk Manag, 2018, 14: 219-224.
19. Braly HL, O’Connor DP, Brinker MR. Percutaneous autologous bone marrow injection in the treatment of distal meta-diaphyseal tibial nonunions and delayed unions. J Orthop Trauma, 2013, 27(9): 527-533.
20. Gross JB, Diligent J, Bensoussan D, et al. Percutaneous autologous bone marrow injection for treatment of delayed and non-union of long bone: a retrospective study of 45 cases. Biomed Mater Eng, 2015, 25(1 Suppl): 187-197.
21. Olivier M, Gay AM, Cerlier A, et al. Can we achieve bone healing using the diamong concept without bone grafting for recalcitrant tibial nonunions? Injury, 2015, 46(7): 1383-1388.
22. Schäfer R, DeBaun MR, Fleck E, et al. Quantitation of progenitor cell populations and growth factors after bone marrow aspirate concentration. J Transl Med, 2019, 17(1): 115.
23. Ling HS, Bolander J, Rustom LE, et al. Bone regeneration strategies: Engineered scaffolds, bioactive molecules and stem cells current stage and future perspectives. Biomaterials, 2018, 180: 143-162.
24. 王福科, 张红, 李彦林, 等. 联合培养血管内皮细胞与脂肪干细胞构建组织工程骨移位成骨. 中国修复重建外科杂志, 2019, 33(10): 1310-1319.
25. 伋琳, 宋辛维, 曾富海, 等. 生长因子控制释放对骨再生影响的研究进展. 中国修复重建外科杂志, 2019, 33(6): 750-755.
26. 倘艳锋, 李无阴, 李建明, 等. 自体生物活性浓集物局部注射治疗骨折延迟愈合的疗效分析. 中国现代医学杂志, 2015, 25(32): 105-108.
27. 倘艳锋, 杨玉霞, 李红军, 等. 经皮骨折断端骨皮质“刺削”并局部注射自体浓缩骨髓液和富血小板血浆混合物治疗骨折延迟愈合. 中华创伤骨科杂志, 2018, 20(11): 999-1003.

Chinese Journal of Reparative and Reconstructive Surgery

Effectiveness of percutaneous injection of autologous concentrated bone marrow aspirate combined with platelet-rich plasma in treatment of delayed fracture healing

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