Chinese Journal of Tissue Engineering Research November 28, 2017 Vol.21, No.33

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1 Chinese Journal of Tissue Engineering Research November 28, 2017 Vol.21, No.33 ( ). [J] (33): DOI: /j.issn ORCID: () L L :R394.2 :B : (2017) Ficat MR CT X Harris SF-36 ( S ) (NCT ) ( )(Z ) (2017YFC )(2016TM-015) ( ) (2017FC-TSYS-2007) Ma Ning, Master, Attending physician, Institute of Orthopedics, Chinese PLA General Hospital, Beijing , China Corresponding author: Peng Jiang, Institute of Orthopedics, Chinese PLA General Hospital, Beijing , China 5388 P.O. Box 10002, Shenyang

2 . Local administration of mononuclear cell, platelet-rich plasma and zoledronic acid for the prevention and treatment of early femoral head osteonecrosis and collapse: study protocol for a prospective, randomized, parallel, controlled clinical trial Ma Ning, Wang Hong-xia, Lu Qiang, Chen Si, Wan Yi-qun, Liu Ying-ying, Wang Xin, Peng Jiang, Guo Quan-yi (Institute of Orthopedics, Chinese PLA General Hospital, Beijing , China) Abstract BACKGROUND: There are various treatment methods for osteonecrosis of the femoral head (ONFH) and collapse, but conservative treatment is invalid. Once femoral head collapse occurs, the development is irreversible. Our previous research has shown that local administration of zoledronic acid can prevent necrotic femoral head collapse. Moreover, bone marrow mononuclear cells obtain satisfactory short-term efficacy in the treatment of ONFH. OBJECTIVE: To investigate the curative efficacy of local administration of mononuclear cell, platelet-rich plasma and zoledronic acid for the prevention and treatment of early ONFH and collapse. METHODS: This prospective, single-center, randomized, parallel, controlled clinical trial was conducted at the Chinese PLA General Hospital, Beijing, China. One hundred patients with ONFH (stages I II by Ficat and Arlet classification) were enrolled and randomly assigned into either the treatment group or control group (n=50 per group). Patients were given an injection of mononuclear cell, platelet-rich plasma and zoledronic acid into the necrotic femoral head, or drilling decompression at the necrotic area. Patients in both groups were then followed up for 4, 8, 12, and 18 months. The primary outcome measures were the blood supply, osteogenesis and appearance of the necrotic femoral head observed on hip perfusion by dynamic MRI, CT restruction of the hip joint and radiography of the hip joint, as well as Harris hip scores and numerical rating scale scores. Secondary outcome measures included SF-36 Health Survey and Activities of Daily Living scores. DISCUSSION: The outcomes of this trial have provided quantitative data for analyzing the effectiveness of local administration of mononuclear cell, platelet-rich plasma and zoledronic acid on ONFH and collapse. Written approval for this protocol was obtained from the Ethics Committee of the Chinese PLA General Hospital in China (approval No. S ). Participants and their families are informed of the study protocol and procedures, and signed an informed consent. The study was in accordance with the guidelines of the Declaration of Helsinki, formulated by the World Medical Association. Trial began in January 2015 and will be completed in December Trial results will be published in scientific reports, or in peer-reviewed journals. This trial was registered with the ClinicalTrials.gov identifier: NCT Patient recruitment is ongoing. Subject headings: Tissue Engineering; Femur Head Necrosis; Femur Funding: the Scientific and Technological Project of Beijing, No. Z ; the National Natural Science Foundation of China, No ; the National Key Development and Research Program of China, No. 2017YFC ; the Translational Foundation of Chinese PLA Hospital, No. 2016TM-015; the Natural Science Foundation of Beijing, No ; the Clinical Supporting Foundation of Chinese PLA General Hospital, No. 2017FC-TSYS-2007 Cite this article: Ma N, Wang HX, Lu Q, Chen S, Wan YQ, Liu YY, Wang X, Peng J, Guo QY. Local administration of mononuclear cell, platelet-rich plasma and zoledronic acid for the prevention and treatment of early femoral head osteonecrosis and collapse: study protocol for a prospective, randomized, parallel, controlled clinical trial. Zhongguo Zuzhi Gongcheng Yanjiu. 2017;21(33): Introduction [1-3] [4-5] [6] [7] [8] (PLGA) [9] [10-11] [12-13] ISSN CN /R CODEN: ZLKHAH 5389

3 . 100 Ficat 18 1Trial design and methods Ficat MR CT X Harris (Numerical rating scale NRS) (1) (2) (3) X CT (Ficat ) [14] (4) (5) (6) (7) (1) (2) (3) () (4)() (5) (6) (7)( ) (8)1 (9) (1) (2) SPSS 19.0 ( 1)2 C X (n=100) (n=50) (n=50) MR CT X Harris NRS SF-36 1 Figure 1 Trial flow chart ml () ml1 ( )() ml cm ml 200 ml (COBE 2991 TM Cell Processor GAMBRO BCT Inc.) r/min5 10 min ( 5390 P.O. Box 10002, Shenyang

4 . PRP) (bone marrow derived stroma cell BMSC) VE(mL) 2 SV(super out volume, ml/min) RT(super out rate min) VE=SV RT ml 2 ml 2 5 ml (12.2±3.0) 10 9 L -1 (35.2±12.0) 10 9 L (PRP) C X4.0 mm mm 8 G 200 µg 5 10 ml 5 min L (1) MR (2)CT CT (1) SF 36(the MOS Short Form 36) [15] (2)(activities of daily living scale ADL) [16] (3) X (4) Harris [17] (5)NRS [18] Table 1 Timing of outcome assessment / MR CT X Harris NRS SF h SPSS 22.0x _ ±s (q1) (median) (q3) α=0.05 Fishert P < Trial status ISSN CN /R CODEN: ZLKHAH 5391

5 . A B 2 8 X Figure 2 X-ray images of a patient with bilateral femoral head osteonecrosises at 8 months postoperatively A B X Harris Figure 5 Changes of the hip function during 1 8 months postoperatively Harris A B C D 3 8 CT Figure 3 CT images of a patient with bilateral femoral head osteonecrosises at 8 months postoperatively A B 2 CT C D 8 CT CT A B C D 4 8 MRI Figure 4 MRI images of a patient with bilateral femoral head osteonecrosises at 8 months postoperatively A C 8 MRI B D Ficat Harris 5 3 Discussion (Ficat ) [19] () [20] [21] mg [22] 5392 P.O. Box 10002, Shenyang

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