Deproteinized Bovine Bone in Alveolar Bone Critical Size Defect (>2cm) Secondary to Cyst Removal

Deproteinized Bovine Bone for the Treatment of Alveolar Bone Critical Size Defect in Humans: A Randomized Clinical Pilot Study

The aim of this study was to evaluate the effect of the use of deproteinized bovine bone as a filler material of critical-sized (diameter >=20 mm) bony defects derived from the excision of maxillary and mandibular cysts. 20 patients were considered.

Patients were randomly divided into 2 groups according to the type of treatment: the bone defect was filled with granules of deproteinized bovine bone (test); no filling material (control). Clinical parameters were recorded at 7 days, 1, 6 and 12 months after surgery. Radiological follow up consisted of an orthopantomograph and a CT scan taken at the baseline (pre-operatory) and 12 months after surgery.

In order to evaluate the difference in percentage of filling of the bone defect between the two groups, the pre-op and the 1-year radiolucent volumes were evaluated in the CT scans.

Study Overview

• Status: Completed
• Conditions: Maxillary Cyst
• Intervention / Treatment: Biological: Deproteinized bovine bone; Device: granules of deproteinized bovine bone (Bio-Oss)

Detailed Description

The healing of extensive alveolar bone defects secondary to cyst removal is not predictable. Residual voids of various entity may persist. Some Authors proposed the use of grafting materials to reconstitute the loss of hard tissue. The primary objective was to determine the efficacy of bone grafting.The secondary objectives were to evaluate the incidence rate of wound dehiscence, pus drainage, recurrence and other complications 7 and 30 days and 6 months after surgery. Recurrence at 12 months of healing was also evaluated. For all patients included, surgeries were performed in conscious sedation and local anesthesia.Full-thickness flap of the appropriate shape and dimensions were lifted, and the bone exposed. When necessary, osteotomy was done, in order to enucleate the cystic lesion. The residual bone cavity was filled with deproteinized bovine bone (test), or not filled with any graft material (control). The flap was finally repositioned and sutured in order to achieve primary closure.

In both test and control groups antibiotic therapy with amoxicillin tablets of 1 g every 12 hours for six days (alternatively, for allergic patients, clarithromycin 500 mg tablets twice daily were given) and proper analgesics were prescribed. Postoperatory physical, therapy was prescribed as well.

Radiological follow up consisted of an orthopantomography and a CT scan taken at 12 months after surgery.For bone volume evaluation, a computerized method was adopted to compare the pre-operatory and the 12 months post-operatory CT scan. The Digital Imaging and Communication in Medicine (DICOM) obtained files were transferred to a Mac Pro Quad 2.66- GHz work- station (Apple Corp., Cupertino, CA, USA) and analyzed using an open-source medical image processing software (OsiriX v. 5.8.5, Pixmeo Sarl, Bernex, Switzerland). The margin of the radiolucent areas of each CT slice was traced manually on each axial view, and the volume calculated by the software with the ROI (Region Of Interest) tool. Volumes in mm3 and 3D images were obtained for each pre-op and post-op ct scan, for every test and control patient. Each exam was evaluated by two assessors (GL and SR) who were trained in radiological diagnosis and measurement detection. The volumetric reduction of the cysts was calculated by subtracting the preoperatory from the post operatory volumes, both in test and control groups.

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Phase 2

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• no smoking for at least 6 months;
• preoperative radiological diagnosis of radiolucent lesion of probable cystic origin;
• bone defect > 2 cm (diameter);
• ASA1;
• consent to the study inclusion.

Exclusion Criteria:

• subjects in need of treatment with a hemostatic material;
• active infection or inflammation in the treatment area;
• uncontrolled diabetes;
• bone diseases ( Paget's disease, patients undergoing bisphosphonate therapy, multiple myeloma, bone metastases);
• previous radiation therapy in the head and neck region;
• patients not able to take part to the follow-up program.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Test Group; The bone defect was filled with granules of deproteinized bovine bone (Bio-Oss, Geistlich Pharm, AG Wolhausen, Switzerland)	Biological: Deproteinized bovine bone; cyst removal followed by heterologous bone grafting; Device: granules of deproteinized bovine bone (Bio-Oss)
No Intervention: Control Group; No filling material was used in the bone healing

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Bone volume evaluation	A computerized method was adopted to compare the pre-operatory and the 12 months post-operatory CT scan. The Digital Imaging and Communication in Medicine (DICOM) obtained files were transferred to a Mac Pro Quad 2.66- GHz work- station (Apple Corp., Cupertino, CA, USA) and analyzed using an open-source medical image processing software (OsiriX v. 5.8.5, Pixmeo Sarl, Bernex, Switzerland) (Lizio et al, 2013; Bittermann et al, 2014). The margin of the radiolucent areas of each CT slice was traced manually on each axial view, and the volume calculated by the software with the ROI (Region Of Interest) tool. Volumes in mm3 and 3D images were obtained for each pre-op and post-op ct scan, for every test and control patient. Each exam was evaluated by two assessors who were trained in radiological diagnosis and measurement detection. The volumetric reduction of the cysts was calculated by subtracting the preoperatory from the post operatory volumes, both in test and control groups.	one year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
physiological parameter (wound dehiscence)	clinical evaluation (present/absent)	7 days, 1, 6 and 12 months after surgery
physiological parameter (pus drainage)	clinical evaluation (present/absent)	7 days, 1, 6 and 12 months after surgery
physiological parameter (recurrence)	clinical evaluation (present/absent)	7 days, 1, 6 and 12 months after surgery
physiological parameter (any other clinical complications)	clinical evaluation (present/absent)	7 days, 1, 6 and 12 months after surgery
bone density (scale - Hounsfield units)	Bone density analysis was conducted on three tomographic axial images (middle, caudal, cranial) of the healed cystic volume, per each patient of both groups. Bone density in Hounsfield Unit (HU) was obtained with the RadiAnt DICOM Viewer software (RadiAnt DICOM Viewer, version 1.1.8; Meixant, Poznan, Poland)	12 months after surgery

Collaborators and Investigators

• Sponsor: University of Padova, School of Dental Medicine
• Collaborators: Geistlich Pharma AG

Study record dates

Study Major Dates

• Study Start: April 1, 2010
• Primary Completion (Actual): December 1, 2014
• Study Completion (Actual): October 1, 2016

Study Registration Dates

• First Submitted: September 21, 2015
• First Submitted That Met QC Criteria: November 23, 2015
• First Posted (Estimate): November 24, 2015

Study Record Updates

• Last Update Posted (Actual): November 12, 2020
• Last Update Submitted That Met QC Criteria: November 9, 2020
• Last Verified: November 1, 2020

More Information

Terms related to this study

• Keywords: bone grafting; alveolar bone; cyst; Bio Oss; critical-size defect; CT bone analysis
• Additional Relevant MeSH Terms: Neoplasms; Pathological Conditions, Anatomical; Cysts
• Other Study ID Numbers: 2187P