Introduction

Long bone nonunion is among the most devastating complications of traumatic fractures, and its treatment remains a major challenge for orthopedic surgeons and physical therapists. The nonunion rates for humerus, femur, and tibia fractures are approximately 2-6%, 2-8%, and 3-6.4%, respectively. Despite numerous proposed methods for managing long bone fracture nonunion, the problem remains unresolved. These fractures represent a significant economic burden on the healthcare system, with reported expenditures of $31,132 USD, $34,440 USD, and $32,660 USD for humerus, femur, and tibia fractures, respectively. Taking preventative measures to avoid this problem is considered the best approach. This is achieved by keeping the fracture site aligned using internal or external fixators. Necrotic debridement and methods of maintaining the alignment of infected tissue and fracture areas with intramodular nails are among the successfully applied techniques. Despite these surgical techniques, nonunion can still occur to a certain extent. Several treatment models with interesting results have recently emerged, including electromagnetic applications, biodegradable implants, and platelet-rich plasma (PRP). PRP is an autologous treatment method performed with a high concentration of activated platelets (approximately 1.2 million platelet cells in 1 ml of plasma) containing beneficial factors such as platelet-derived growth factor (PDGF), vascular endothelial growth factor (VEGF), epidermal growth factor (EGF), fibroblast growth factor (FGF), and transforming growth factor (TGF-β1, TGF-β2), which are responsible for tissue formation and repair in the human body. PRP is successfully used in musculoskeletal injuries. Many scientific studies have reported interesting results from PRP applications for the treatment of bone nonunion cases. Although some studies have shown that PRP increases the healing rate of fractures, other studies have suggested that PRP has no effect. Therefore, this study aims to determine the effects and healing rates of PRP application in cases of nonunion of long bone fractures.

Materials and Methods

Participation Rate: This study is a 17-month (May 2011 to October 2012) clinical trial conducted at the Shahid Rajee Trauma Center (Level I Trauma Center) with contributions from the Department of Medical Sciences, Shiraz University. The study protocol was approved by the Institutional Inspection Board (IRB) and the AJA University Health Sciences Ethics Committee, and written consent was obtained from all participants. This study was also registered with the Iranian Clinical Study Organization (IRCT201208262445N1; www.irct.ir). This study included 79 adult patients over 18 years of age who had experienced non-union of long bone (femur, tibia, humerus, ulna) fractures for more than 6 months. Patients under 18 years of age, those with infections, vascular disease, extensive skin ulcers at the fracture site, musculoskeletal disorders, pathological fractures, tumors, large fractures, and active immune system disorders were excluded. Additionally, patients with platelet counts less than 100,000 platelets/ml and greater than 650,000 platelets/ml, and those who had received growth factor, steroid, or AIDS treatment within the last year were also excluded.

Randomness and Intervention

Patients included in this study were randomly assigned to two study groups, with each patient's registration number randomly assigned by a computer-assisted digitizer. In the PRP group (37 patients), 5 mL of PRP was taken, and in the placebo group (38 patients), normal saline was taken as a placebo from the fracture site or the open reduction and internal fixation site after intramodular nailing.

Study Protocol and Measurements

All patients included in the study underwent the same physiotherapy treatment one day prior to the operation. Important information such as age and gender, as well as clinical characteristics (fracture site, mechanism of injury, previous surgeries, duration of fracture), were recorded. 5 mL of blood was also taken from each patient to determine hemoglobin and platelet counts. Autologous PRP was prepared using a Gravity Platelet Separation System according to the manufacturer's protocol. In total, 54 mL of blood was drawn from the right cubital vein into citric acid-containing tubes during the operation. To separate platelets from red blood cells and plasma, the blood-filled tubes were rapidly centrifuged at 3200 rpm for 15 minutes. Approximately 5-6 mL of PRP was obtained and transferred to a syringe. It was proven that the platelet concentration in the PRP was 4.2-4.8 times higher than normal blood levels. General anesthesia was administered to all patients using the standard protocol.