Abstract: BACKGROUND: Due to the super-healing effect, platelet-rich plasma is gradually used in the clinic. Nevertheless, high-quality clinical comparative studies are currently absent to identify its effect on fracture nonunion and its action mechanism.
OBJECTIVE: To compare the effects between platelet-rich plasma combined with surgery and surgery alone in the treatment of nonunion after tibial shaft fractures, and to analyze the corresponding laboratory indicators of fracture repair. 
METHODS: Thirty patients with nonunion of tibial shaft fractures treated in Weihai Central Hospital Affiliated to Qingdao University from January 2017 to January 2020 were enrolled in this study. According to the second operation method, these patients were divided into platelet-rich plasma combined surgery group (n=16; autologous platelet-rich plasma injection once every other week for three injections) and operation group (n=14). Blood samples were taken from patients of the two groups to detect the levels of osteocalcin, bone alkaline phosphatase and β-I collagen carboxyl terminal peptide on the day of surgery (before surgery) and at 2, 4, 8, and 12 weeks after surgery. The surgical incision healing of the patients was observed between the two groups. At 3, 6, and 9 months after surgery, the callus and fracture line imaging scores and visual analogue scale scores were analyzed in the two groups, and the clinical healing and bone healing time were recorded in the two groups. The protocol was approved by the Ethics Committee of Weihai Central Hospital Affiliated to Qingdao University (approval No. 2016-Lunshen-07). 
RESULTS AND CONCLUSION: (1) The levels of serum osteocalcin, bone alkaline phosphatase and β-I collagen carboxyl terminal peptide increased in the two groups after surgery. The osteocalcin level in the platelet-rich plasma combined surgery group was higher than that in the operation group at 2 and 4 weeks after surgery (P < 0.05). Bone alkaline phosphatase was higher in the platelet-rich plasma combined surgery group than that in the operation group at 2, 4, and 8 weeks after surgery (P < 0.05). The β-I collagen carboxyl terminal peptide level was higher in the platelet-rich plasma combined surgery group than that in the operation group after surgery (P < 0.05). (2) The grade A healing rates of incisions were 88% and 64% in the platelet-rich plasma combined surgery group and the operation group, respectively. The clinical fracture healing time and bone healing time were shorter in the platelet-rich plasma combined surgery group than those in the operation group (P < 0.05). (3) The imaging scores of callus and fracture line were higher in the platelet-rich plasma combined surgery group than those of the operation group at 3, 6, and 9 months after surgery (P < 0.05). Visual analogue scale scores were lower in the platelet-rich plasma combined surgery group than those of the operation group (P < 0.05). (4) These findings indicate that the effect of platelet-rich plasma combined with surgery for nonunion of tibial shaft fractures is better than that of surgery alone. Their combination can increase the serum levels of osteocalcin, bone alkaline phosphatase, and β-I collagen carboxyl terminal peptide, and is helpful to investigate the mechanism of platelet-rich plasma for fracture nonunion and to judge the clinical prognosis. 

Key words: tibial fracture, fracture nonunion, platelet-rich plasma, bone turnover marker, osteocalcin, bone alkaline phosphatase, β-I collagen carboxy-terminal peptide, internal fixation