Evaluation of the Osteoinductivity of Atorvastatin Combined With β-TCP

Evaluation of the Osteoinductivity of Atorvastatin Combined With β-TCP in the Treatment of Bone Defects After Radicular Jaw Cyst Enucleation Using CBCT-based Volumetric Analysis

This case series study aims to evaluate the local effects of Atorvastatin (which belongs to the family of lipid-lowering drugs, known as statins) combined with β-TCP (which is a synthetic osteoconductive bone graft), on the volume of the residual bone defects and on hastening the bone regeneration after radicular jaw cyst enucleation using CBCT-based volumetric analysis to calculate the shrinkage rate of these defects.

Study Overview

• Status: Not yet recruiting
• Conditions: Bone Loss; Infection
• Intervention / Treatment: Procedure: Cyst enucleation and bone grafting

Detailed Description

Statement of the problem:

According to the literature, the residual bone defects after medium-large-sized jaw cyst enucleation pose the risk for infection, insufficient healing, and pathological fracture. the gold standard of bone grafting materials remains the autologous bone graft, yet it is accompanied by risks including second surgery, the morbidity of the donor site, excessive bleeding, etc.

Therefore, there is a constant search for alternative bone grafting materials, this is where the addition of atorvastatin to an osteoconductive synthetic bone grafting material (β-TCP) comes in. β-TCP takes anywhere from 6 to 18 months for complete resorption and replacement by bone, according to the literature.

The addition of an osteoinductive material to an osteoconductive grafting material like β-TCP holds two premises; increasing the resorption of the β-TCP particles at the expense of bone deposition, and therefore leads to hastening the bone generation of the residual bone defects.

Rationale:

Studies have shown that the local application of lipid-lowering drugs, statins, induces bone growth by stimulating BMP-2. therefore, the addition of these pharmacological agents to osteoconductive bone graft materials, which lack osteogenic properties, could be a promising approach for bone regeneration.

However, there is still no consensus in the literature on the optimal therapeutic dose and mode of application for statins. Furthermore, limited studies are available in the literature regarding the use of statins especially Atorvastatin as a biological modifier in filling bone defects after cyst enucleation.

Therefore, the purpose of this study is to validate and evaluate the osteoinductivity of statins+ β-TCP combination using the Gouda et al., methodology used in maxillary sinus lifting using simvastatin but instead using atorvastatin in filling the residual defects of medium-large odontogenic radicular cysts (1.5 - 4 cm), which shows the suppressive influence on bone formation, as well as a greater risk for pathological fracture, infection, and insufficient bone healing.

Methodology:

The ratio of atorvastatin to β-TCP will be 0.1 mg: 14 mg, which was the methodology adopted by Gouda et al, based on the methodology of Nyan et al.

• Study Type: Interventional
• Enrollment (Estimated): 10
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Yara Mahmoud; Phone Number: 01100764737; Email: yara.mahmoud@dentistry.cu.edu.eg
• Study Contact Backup: Name: Mohamed Mosa; Email: mohamed.mosa@dentistry.cu.edu.eg

Study Locations

• Egypt
  • Cairo, Egypt
    • Cairo University
    • Contact: Phone Number: 23634965; Email: surgery@dentistry.cu.edu.eg

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

1. Male and female patients
2. Patients 18 to 40 years old
3. Radicular cyst with a maximum diameter from 1.5 to 4.0 cm;
4. Focal teeth were preserved with root canal treatment;
5. No previous surgical treatment of the cyst site;
6. No evidence of acute inflammation;
7. In good physical status and oral health;
8. Regular attendance at control visits

Exclusion Criteria:

1. Patients < 17 years old
2. Radicular cyst with a maximum diameter < 1.5 cm.
3. Pregnancy or lactation
4. Aggregate systemic pathologies such as diabetes, thyroid disorders, and bone metabolism diseases, among others;
5. Patients taking calcium, bisphosphonates, glucocorticoids, or other drugs that can interfere with the metabolism of bone;
6. Patients with uncontrolled periodontal conditions, endodontic conditions, and other oral disorders;
7. Heavy smokers (10 cigarettes/day or more)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: bone grafting using atorvastatin combined with beta-TCP; the 10 volunteers will undergo cyst enucleation followed by filling the residual bone defects with atorvastatin combined with beta-TCP in the ratio of 0.1 mg: 14 mg.	Procedure: Cyst enucleation and bone grafting; cyst enucleation followed by bone grafting the residual bone defects using Atorvastatin combined with β-TCP.; Other Names: Bone grafting

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The Rate of shrinkage of the residual bone defect	the shrinkage of the residual bone defects after bone grafting, measured from the following formula: pre-operative cyst volume - 3/6 months post-operative defect volume/pre-operative cyst volume x 100%. it will be measured radiographically using CBCT through manual segmentation	3 moths post-operatively and 6 months post-operatively

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Inflammation at the grafted site	any signs of inflammation; edema, redness or discharge	1 week post-operatively, 3 months post-operatively and 6 months post-operatively

Collaborators and Investigators

• Sponsor: Cairo University
• Investigators: Study Director: Salah Yassin, department of oral and maxillofacial surgery, cairo university

Publications and helpful links

Helpful Links

• first in-vivo study to test the methodology adopted in this research
• the clinical study methodology adopted in this research

Study record dates

Study Major Dates

• Study Start (Estimated): December 1, 2024
• Primary Completion (Estimated): December 1, 2025
• Study Completion (Estimated): March 1, 2026

Study Registration Dates

• First Submitted: April 22, 2024
• First Submitted That Met QC Criteria: April 22, 2024
• First Posted (Actual): April 25, 2024

Study Record Updates

• Last Update Posted (Actual): August 13, 2024
• Last Update Submitted That Met QC Criteria: August 11, 2024
• Last Verified: August 1, 2024

More Information

Terms related to this study

• Keywords: bone graft; volumetric analysis; bone regeneration
• Other Study ID Numbers: 3-3-14

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No