IntroductionUnion of long bone fractures is a complicated biological mechanism affected by numerous systemic and local variables. Disruption of any of these components may result in fracture nonunion. There are various types of clinically available treatment strategies for aseptic nonunion. Both activated platelet plasma and extracorporeal shock waves play important roles in fracture healing. This study aimed to investigate the interaction of Platelet-rich plasma (PRP) and extracorporeal shock wave (ESW) in bone healing of nonunion. HypothesisPRP and ESW have synergistic effects in treating long bone nonunion. MethodsBetween January 2016 and December 2021, a total of 60 patients with established nonunion of a long bone (18 tibias, 15 femurs, 9 humerus, 6 radii, and 12 ulnae) were included in this study, comprising 31 males and 29 females, ranging from 18 to 60 years old. Patients with bone nonunion were separated into two groups: PRP alone (Monotherapy group) and those treated with PRP combined with ESW (Combined treatment group). The two groups were compared to assess the therapeutic benefits, callus development, local problems, bone healing time, and Johner Wruhs functional classification of operated limbs. ResultsFifty-five patients were followed up, 5 patients were lost to follow-up, two in the PRP group and three in the PRP+ESW group, the follow-up time varied from 6 to 18 months, with an average of 12.7±5.2months. At 8, 12, 16, 20, and 24weeks following intervention, the callus score in the monotherapy group was significantly lower than in the combined treatment group (p<0.05). Both groups had no swelling and infection in the soft tissue of the nonunion operation site. In the PRP+ESW group, the fracture union rate was 92.59 % and the healing time was 16.3±5.2 weeks. In the PRP group, the fracture union rate was 71.43 % and the healing time was 21.5±3.7 weeks. The clinical healing time of the monotherapy group was significantly longer than the combined treatment group (p<0.05). All the nonunion patients with no signs of healing were treated with revision surgery. The excellent and good rate of Johner-Wruhs functional classification of affected limbs in the monotherapy group was significantly lower than in the combined treatment group (p<0.05). ConclusionPRP combined with ESW has a certain synergistic effect in treating aseptic nonunion after fracture surgery. It can significantly improve the formation of new bone, it is a minimally invasive and effective strategy to treat aseptic nonunion in a clinical setting. Level of evidenceIII, retrospective, single-centre, case-control study.