Can calcitonin nasal spray reduce the risk of recurrence of central giant cell granuloma of the jaws? A double-blind clinical trial

Abstract

Recurrence is a major problem following the treatment of aggressive central giant cell granuloma (CGCG). The aim of this study was to compare the frequency of recurrence between patients who received calcitonin nasal spray after curettage of CGCGs and those who did not. A double-blind clinical trial was designed. Patients were allocated to one of two groups: those in the calcitonin group underwent curettage and received calcitonin salmon nasal spray 200 IU/day once a day for 3 months after surgery; those in the control group underwent curettage of CGCGs and received a placebo once a day for 3 months after surgery. All patients were followed for 5 years after surgery. Twenty-four patients were treated in the two groups. There was no difference in age, sex, tumour size, or tumour location between the two groups ( P > 0.05). Eight of the 24 patients (33.3%) had recurrences during the follow-up period: one in the calcitonin group (9.1%) and seven in the control group (53.8%). Analysis of the data demonstrated a significant difference between the two study groups ( P = 0.033). It appears that calcitonin nasal spray may reduce the frequency of recurrence in aggressive CGCGs in the mandible and maxilla.

Central giant cell granuloma (CGCG) is a benign lesion of the jawbones. The incidence of CGCG is about 0.00011% of the general population. CGCGs have variable behaviours and clinical presentations, ranging from large lesions with aggressive behaviour to small isolated lesions. The clinical signs and symptoms and the radiographic and histological features are the main factors differentiating non-aggressive (indolent) from more aggressive lesions. Lesions larger than 5 cm and/or recurrent lesions are considered aggressive lesions based on clinical characteristics. The non-aggressive lesions are asymptomatic with no radiographically visible cortical perforation or root resorption.

Local curettage is the conventional treatment for CGCGs. En bloc resection has been suggested for aggressive CGCGs. The recurrence rate following local curettage in aggressive CGCGs is between 16% and 48%. En bloc resection is associated with the lowest recurrence rate. However, en bloc resection results in various degrees of deformity and requires complex reconstruction procedures.

In the past two decades, various pharmacological therapies for CGCGs have been described. Pharmacological agents prevent or at least minimize the extensive and mutilating surgical procedures characterized by detrimental functional outcomes and preserve vital structures and facial contours. Pharmacological agents that have been used successfully include intra-lesional corticosteroid injections and systemic treatment with calcitonin or interferon alpha-2a (IFN-α2a). Harris introduced calcitonin therapy for CGCGs. The mode of action of calcitonin in the treatment of CGCGs is antagonistic osteoclastic bone resorption, or direct action on other cell types within the lesion. Calcitonin has been considered a viable option for the treatment of CGCGs. It is suggested for multiple lesions, recurrent lesions, and aggressive lesions.

In studies reported in the literature, calcitonin has been applied for the treatment of CGCGs either alone or as an adjunct agent. However, it has not been used to prevent recurrence in the management of CGCGs. Thus, this study was performed to assess the use of calcitonin after curettage of aggressive CGCGs to determine whether it reduces the frequency of recurrence or not. It was hypothesized that calcitonin would decrease recurrence after conventional curettage of CGCGs of the jaws.

Materials and methods

A double-blind randomized clinical trial was designed. The sample was derived from the population of patients referred to the oral and maxillofacial surgery department of a medical university in Shiraz, Iran, between 1 September 2006 and 31 October 2010. The study was approved by the necessary medical ethics committee and has been registered at ClinicalTrials.gov (registration ID NCT02358304 ).

Subjects eligible for inclusion had a clinically aggressive CGCG and underwent curettage. All subjects had computed tomography (CT) scans taken before surgery. Participants with a systemic disease affecting bone healing, a brown tumour proven by laboratory test (parathyroid hormone, calcium phosphatase), pregnancy, recent corticosteroid therapy, and those who refused enrolment or could not continue for private or social reasons, were excluded from the study.

The diagnosis of CGCG was made initially by histopathological examination. Aggressive CGCGs were defined as lesions with a diameter >5 cm on CT scan views, with perforation of the buccal and lingual plates or root resorption.

Thirty patients were allocated randomly to two groups. Patients in the calcitonin group ( n = 15) underwent curettage of CGCGs and received calcitonin salmon nasal spray 200 IU/day once a day for 3 months after the surgery. Patients in the control group ( n = 15) underwent curettage of CGCGs and received a placebo once a day for 3 months after surgery. Patients were followed by a maxillofacial surgeon who did not participate in the surgeries and was blinded to the group allocation of subjects. Furthermore, none of these surgeons was aware of the research. Patients were blinded to the type of drugs they had received after surgery.

All patients were followed up for 5 years after the operations. Cases of recurrence were documented by clinical and radiographic examinations and confirmed by histopathological analysis.

Age, sex, location (maxilla or mandible), and tumour size were considered as variables. Calcitonin was the predictive factor of the study. Recurrence of the CGCGs determined the outcome of the study.

Statistical analysis

Statistical analyses were performed using IBM SPSS Statistics for Windows, version 19.0 (IBM Corp., Armonk, NY, USA). A pre-protocol analysis was conducted. The Shapiro–Wilk test was used to document normally distributed age of the samples. The independent t -test was applied to compare age and tumour size between the groups (treatment group with calcitonin and control group). Fisher’s exact test was applied to assess the frequency of recurrence and variables (tumour location and sex) between the two groups.

Results

A final total of 24 patients were studied in the two groups: 11 in the calcitonin group and 13 in the control group. Six of the initial 30 patients dropped out at random; these patients did not follow the study protocol, or failed to complete the follow-up. The calcitonin group (treatment group) comprised five males and six females and the control group comprised six males and seven females. There was no difference between the two groups in sex distribution ( P = 0.64). The mean patient age was 24.36 ± 4.29 years in the calcitonin group and 24.61 ± 4.64 years in the control group. Comparison of the mean age between the groups did not show a statistically significant difference ( P = 0.83) ( Table 1 ).

Table 1
Comparison of variables between the two groups.
Variables Group 1
Calcitonin group
Group 2
Control group
P -value
Tumour location 0.47 a
Mandible 4 6
Maxilla 7 7
Sex 0.64 a
Male 5 6
Female 6 7
Tumour size, mean ± SD (cm) 6.40 ± 0.88 6.26 ± 0.97 0.71 b
Age, mean ± SD (years) 24.36 ± 4.29 24.61 ± 4.64 0.83 b
SD, standard deviation.

a Fisher’s exact test.

b Independent t -test.

The mean tumour size was 6.40 ± 0.88 cm in the calcitonin group and 6.26 ± 0.97 cm in the control group. Evaluation of tumour size did not demonstrate a significant difference between the groups ( P = 0.71). In the calcitonin group, seven patients had CGCGs in the maxilla and four had CGCGs in the mandible. In the control group, seven patients had CGCGs in the maxilla and six had CGCGs in the mandible. There was no statistically significant difference in tumour location (maxilla or mandible) between the groups ( P = 0.47) ( Table 1 ).

The mean time to recurrence was 23.5 ± 8.75 months ( Table 2 ). Eight of 24 patients (33.3%) had a recurrence. One patient (9.1%) in the calcitonin group and seven patients (53.8%) in the control group had a recurrence during the 5-year follow-up. Analysis of the data demonstrated a significant difference between the two groups in this regard ( P = 0.033) ( Table 3 ). All patients with recurrence underwent en bloc resection. None of the patients with a resected lesion had a secondary recurrence.

Table 2
Description of the patients with recurrence.
Recurrence case Group Sex Age (years) Site Time of recurrence (months) Tumour size (cm)
1 1 Female 24 Maxilla 33 8
2 2 Female 29 Maxilla 27 7
3 2 Male 19 Maxilla 18 8
4 2 Male 28 Maxilla 26 7
5 2 Female 18 Maxilla 10 7
6 2 Male 26 Maxilla 22 6
7 2 Male 25 Maxilla 36 6
8 2 Female 22 Maxilla 16 7

Jan 16, 2018 | Posted by in Oral and Maxillofacial Surgery | Comments Off on Can calcitonin nasal spray reduce the risk of recurrence of central giant cell granuloma of the jaws? A double-blind clinical trial
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