Table 3.
Synopsis of delayed union studies included in the present review.
| Publication | Study type (LoE) | Total patients | Age | Pathology | Therapeutic protocol | Protocol specifics | Orthobiologic type | FU (months) | Main findings |
|---|---|---|---|---|---|---|---|---|---|
| Bielecki T. et al., Eur Surg Res. (2008) | Prospective study (IV) | 12 (8 M, 4 F) | 19–60 (mean 41,4) | Long bone delayed union: 9 tibias and 3 fibulas | PLRG injection | An 18-gauge or biopsy needle was introduced immediately into the gap of delayed union or nonunion under fluoroscopic guidance. In all cases, PLRP and thrombin solution (a total of 15 mL) was injected by dual syringe applicator system (Biomet Inc.) into the disturbed bone-healing area forming a gelatinous mass | Platelet-Leukocyte-Rich Gel (PLRG) | Day 3 as well as 3, 5, 8, 12, 18 and 24 weeks after percutaneous PLRG injection. | In the delayed union group, the average time to union was 9.3 weeks after PLRG injection, and union was achieved in all cases. In the nonunion group, union was observed in 13 out of 20 cases, with an average time to union of 10.3 weeks after PLRG injection. Interestingly, in patients where union was not achieved, the average time from the fracture and/or the last operation was over 11 months. Fortunately, no complications were observed. |
| Golos et al., Ortopedia Traumatologia (2014) | Prospective study (IV) | 132 (79M, 53F) | 18–85 (mean 41) | Long bone delayed union: 21 humerus, 32 forearms, 23 femurs, 47 tibias | PRP fluoroscopic guided injection | The patients with diagnosed delayed bone union had platelet rich plasma administered into the fracture cleft. The procedure was performed under radio- graphic guidance with local by the closed percutaneous method | PRP | Radiographs were obtained every 6 weeks until bone union was observed. | Bone union was observed in 108 patients (81.8 %) following PRP administration. The treatment demonstrated its highest efficacy in patients with delayed union of the proximal tibia who underwent surgical intervention with open reduction and plate fixation (100 % success rate), typically achieving union after an average of 3.5 months post-PRP administration. Conversely, the lowest efficacy was noted in patients with delayed union of the proximal humerus who underwent surgical intervention with open reduction and plate fixation (63.64 % success rate), typically achieving union after an average of 3.2 months post-PRP administration. |
| Say et al., Acta Chirurgiae Orthopaedica (2014) | Retrospective case series (IV) | 20 (17M, 3F) | Age 33.5 range 18–77 | Long bone non union: 12 Long bone delayed union: 8 (16 femurs and 4 tibias in total) |
PRP fluoroscopic guided injection | The prepared PRP was injected into the fracture line under fluoroscopy guidance for totally three times once a week. The application of PRP was made at median 6 (range 6–8) months after fracture surgery. | PRP | Median period of 11 (range 8–12) months | During the follow-up period, eleven patients experienced non-union of the fracture and required revision surgery. Radiological and clinical evidence of sufficient union was not observed in three patients. Among the delayed union group, six out of eight patients achieved fracture union. Notably, no patient in the non-union group attained fracture union. |
| Carlos Acosta-Olivo et al., Arch Orthop Trauma Surg (2017) | RCT (I) | 16 (13M, 3F) | 21–60 (mean 38.1) | Humerus delayed union | ICA (9) vs ICA + PRP (7) | LCP fixation with an ICA was performed in the control group; this treatment was supplemented with the intraoperative administration of 12 mL of autologous PRP in the study group. All the patients were subjected to the same initial surgical procedure. | PRP | 2, 4, 6, 12, 24, and 36 weeks of evolution. | Patients treated with PRP showed an earlier onset of bone consolidation, with signs evident at 2 weeks compared to 6 weeks in the control group. Additionally, these patients achieved bone consolidation at an average of 19.9 weeks, whereas the control group required 25.4 weeks on average. Importantly, the experimental group achieved union in 100 % of cases, with only one patient failing to achieve union. Clinical scores were similar between the two groups. |
| Samuel G. et al., European Journal of Orthopaedic Surgery & Traumatology (2018) | RCT (I) | 40 (39M, 1 F) | 20–60 (mean 37) | Long bone delayed union (Femurs 29, Tibias 8, Forearms 2, Humerus 1) | PC 23 (percutaneous injection under fluoroscopic guidance) vs Observation 17 |
Before injection the prepared PC is activated by adding 10 % calcium gluconate in the ratio 3:10, following which the PC is loaded into a 10-mL syringe and injected percutaneously at the delayed union site under image intensifier guidance. The study group patients are given a second and final PC injection at the delayed union site at 3 weeks from the first injection by repeating the same procedure. | PC (Platelet Concentrate) | Every 6 weeks until fracture union | The percentage of union was 78 % (18 out of 23) in the PC group and 59 % (10 out of 17) in the control group (p = 0.296). The mean time to fracture union treated with PC (15.33 ± 9.91 weeks) did not differ significantly from the control group (13.10 ± 7.21 weeks; p = 0.540). In the PC group, union was observed in 60 % of cases after 12 weeks following PC injection. |
| Canton et al., Acta Biomed (2023) | Case series (V) | 11 (4M, 7F) | 46–84 (mean 61) | Long bone delayed union and 8 non union (femurs 36 %, tibias 45 %, other long bones where humerus and clavicle). | Surgery + BMAC | 2 patients were treated with circular external fixator and percutaneous injection of BMAC alone. All other patients received the combination of internal fixation (plate/nail) and cancellous allograft with BMAC supplementation | BMAC | 6,5 months (until union occurred) | All 11 patients (100 %) achieved union after treatment, with a mean time to radiographic union of 6.5 months (range 4–12). Notably, none of the patients experienced complications during the evaluation period. Specifically, there were no instances of donor site morbidity, hematoma, or wound complications at the iliac crest BMAC harvesting site. |
| Ranjan R. et al., Journal of Orthopedics (2023) | Case series (V) | 25 (19M, 6F) | 29–63 (mean 40) | Long bone delays union (7 femurs, 4 humerus, 14 tibias) | PRP (fluoroscopic guided injection) | Fractures were augmented with 3 doses of autologous PRP injection with each dose being administered at an interval of 3 weeks. Under c-arm guidance, the delayed union site was localized and an autologous PRP solution is infiltrated. After administering an autologous PRP injection at the fracture site, an external stabilization was given as per the routine management of fractures. | PRP | 12 months | Out of 25 cases, 21 (84.00 %) showed good union of the fracture with adequate callus formation within 10–12 weeks after receiving 3 doses of autologous PRP injections. The mean pre-procedural VAS and Warden's score at the final follow-up revealed statistically significant improvements (p < 0.05). Throughout the study period, no other complications were attributed to autologous PRP application among the study participants, except for 3 cases, which included 2 instances of non-union and 1 case of implant failure. |