Influence of perioperative dexamethasone on delayed union in mandibular fractures: A clinical and radiological study

Background The aim was to clarify the occurrence of delayed union after surgical treatment of mandibular fracture and investigate whether an association exists between perioperative use of dexamethasone and delayed union. Material and Methods Thirty-seven patients were included in a prospective randomized study. Of these patients, 19 (51.4%) were randomized to receive a total dose of 30 mg of dexamethasone and 18 (48.6%) served as controls. Patients underwent clinical and radiological investigation immediately, one month, three months and six months postoperatively. Radiographs were evaluated by an experienced, blinded senior oral radiologist. Results Delayed fracture union was found in 9 patients (24.3%). It was associated significantly with angle fractures (p=0.012). Delayed union occurred more frequently in patients who received dexamethasone (36.8%) than in those who did not (11.1%) (p=0.068). The association of infection with delayed union was significant (p=0.027). Moreover, dexamethasone was significantly (p=0.019) associated with delayed fracture union with concomitant infection. Gender, age group, smoking habit, treatment delay and duration of surgery were not associated with delayed union. Conclusions Infection was associated with delayed union. Short-term high-dose dexamethasone predisposed to complicated fracture union, especially in patients with angle fractures. The relationship between dexamethasone and delayed bone healing without infection remains unresolved. Key words:Mandibular, radiology, fracture union, dexamethasone.


Patient and Methods
-Study design Patients included in the study were drawn from a larger cohort of healthy dentate patients aged 18 years or more who had participated in a randomised study aimed at �l���������t�e�be�e�ts�����ex�met��s��e��������,��e�e-m�� ���� ��use�� ��te�� ��e�� �e�u�t���� ���� �x�t���� ��� �� facial fracture. We excluded patients with infected fractures, a history of liver or kidney dysfunction, a history of peptic ulcer, a history of psychosis due to steroid use, pregnancy, breastfeeding or allergy to any constituent of the dexamethasone preparation used. For each facial fracture type, patients were randomly assigned to one of two groups. The patients in the study group received dexamethasone (Oradexon®), whereas patients in the control group received no glucocorticoid. Patients in the study group received a total dose of 30 mg of dexamethasone divided into three doses: 10 mg intravenously during anaesthesia induction and two additional 10 mg doses intramuscularly every 8 hours over 16 hours. All patients received antibiotics until the seventh to tenth postoperative day, starting with three 1.5-g doses of cefuroxime taken intravenously at t�e�������u�����t�e���st������u�s���st��e��t�vel������ followed by three daily doses of 500 mg of cephalexin taken orally. Patients with allergy received four doses of clindamycin via corresponding routes. The patients were scheduled for clinical follow-up at 1 day, 2 days, 1 week, 1 month, 3 months and 6 months after the operation. The clinical examination was conducted by a blinded investigator. In addition, patients were scheduled for panoramic imaging (Soredex Co., Tuusula, Finland) and Towne projection imaging (Samsung XGeo, Suwon, South Korea) preoperatively, immediately after surgery and at 1, 3 and 6 months after surgery. Patients with fractures in the anterior region of the mandible additionally underwent imaging with Scanora zonograms (Soredex Co., Tuusula, Finland).
-Study variables A senior oral radiologist (S.A.) evaluated the radiographs blindly twice with a 2week interval. The radiographs were analysed on a Dome E2 grayscale display �s�ze�1��6″;�Pl�����S�stems,�Be�ve�t��,�OR,�USA����t�� a display resolution of 1200 x 1600 pixels. Since there was no disagreement between the reviews, intraobserver reliability was considered good/excellent. The outcome variables were 1) delayed fracture union (including all patients with delayed fracture union), 2) delayed fracture union with associated infection (including patients with delayed fracture union who at any time during follow-up had an infection at the surgical site) and 3) delayed fracture union without associated infection (including patients who did not have any surgical site infection during follow-up). e623 T�e� �e���t���� ��� ������������� u����� ��s� b�se�� ��� �� combination of the visibility of lucent fracture line, presence of callus and bridging of callus. In fractures involving the symphysis area, presence of callus visible at the inferior margin of the mandible was evaluated from a panoramic radiograph, whereas in angle fractures presence of callus visible on buccal cortical plate was evaluated from a Towne view. Delayed union was established when osteolysis and/or enhanced resorption was evident one month after surgery and/or the fracture line was still clearly visible three months after surgery without bridging of callus. In cases where normal resorption of the fracture line was evident one month postoperatively, but fading of the fracture line and cortical continuity were observed three months postoperatively, the radiographic union was established as successful. The predictor variables were gender, age, smoking habit, fracture site, treatment delay, duration of surgery, perioperative use of dexamethasone and surgical site infection during follow-up.

Results
Of the patients recruited for the initial study, 49 ful-�lle��t�e����lus�������te��������t�e���ese�t����l�s�s��O�� these, 4 refused to participate. Of the remaining 45 patients, 8 were excluded: 4 because they failed to attend the required radiological investigations, one because he required additional surgery due to unsatisfactory fracture reduction, two because they failed to complete all scheduled medical doses, one because of an infection of a tooth situated in the fracture line. Thus, a total of 37 patients were followed up clinically and radiologically for at least 3 months. Descriptive statistics of patients are shown in table 1. A total of 49 fracture lines were diagnosed in 37 patients, angle fractures (n=25) being most frequent. Nineteen patients received dexamethasone. Ten patients had surgical site infection during follow-up. Delayed fracture union was observed in 9 patients (24.3%) (Fig. 1). None of the patients developed nonunion. Table 2 shows the association between predictor variables and delayed fracture union. Surgical site infection (p=0.027) and angle fracture (p=0.012) �e�e�s��������t���e���t��s������el��e��u�������el��e�� fracture union occurred rarely in symphysis fractures (p=0.045). No association was present between delayed fracture union and gender, age group, smoking habit, treatment delay or duration of surgery. Table 3 summarizes the association between predictor variables and delayed fracture union with surgical site infection and delayed fracture union not accompanied b�����e�t������ex�met��s��e���s���s��������t���e���tor for delayed fracture union with associated infection (p=0.019). No other associations were found between examined predictors and delayed fracture union with or without infection.

Discussion
We investigated the occurrence of delayed union after surgical treatment of mandibular fracture and whether an association exists between perioperative use of dexamethasone and delayed union. Delayed union was observed in nine patients (24.3%). It was associated with surgical site infection (p=0.027) and angle fracture (p=0.012). Moreover, the association between dexamethasone use and delayed fracture union ��t�����e�t������s�s��������t��p=0.019).

e626
The angle region was associated with delayed union in e���t�������e���t�e�ts��M��e�ve�,�����ll��ve���t�e�ts����� had delayed union with infection, delayed union was located in the angle region. Fractures in the mandibular angle are known to be associated with more infectious complications (10,11). Ellis showed increased infection risk related to angle fractures when there were wisdom teeth present (12). Also large surface area of the fracture, impaired functions of the periosteum due to fracture and/or dissection, or diastasis of fracture ends might predispose angle fractures to delayed union compared with other parts of the dentate mandible. Careful radiological follow-up is recommended with regular clinical evaluation in patients with angular fractures, especially when potential factors for delayed bone healing are present.
In conclusion, perioperative high-dose dexamethasone predisposed patients to delayed fracture union with concomitant infection at the surgical site. However, the effect of dexamethasone on delayed fracture union without associated infection remains to be elucidated.