Assessment of Osteogenic Potential of Topical Metformin Gel on Bone Regeneration in Cystic Jaw Defects: Randomized Controlled Clinical Trial
| Registry | NCT07867236 |
|---|---|
| Status | Not yet recruiting |
| Phase | Not applicable |
| Study type | Interventional; randomized, parallel, masking: quadruple, treatment |
| Enrollment | 32 (Estimated) |
| Sponsor | Fayoum University (Other) |
| Conditions | Jaw Cysts, Metformin, Inflammatory Cyst, Cyst Enucleation, Odontogenic Cysts |
| Interventions | For the Experimental Arm: 1% Metformin Gel, For the Comparator / Control Arm: Placebo Gel (Drug) |
| Dates | start 2026-10-30 (estimated), primary completion 2027-09-30 (estimated), completion 2027-10-30 (estimated), first posted 2026-10-09, last updated 2026-10-14 |
| Locations | 1 site in Egypt |
Related Papers Related Patents Related Grants Related Experts
All trials for Jaw Cysts All trials for Metformin All trials of For the Experimental Arm: 1% Metformin Gel All trials of For the Comparator / Control Arm: Placebo Gel
Evaluate the osteogenic effect of locally applied 1% metformin gel on bone volume formation after jaw cystic defects enucleation
Odontogenic jaw cysts, represent a significant portion of the pathological lesions encountered in daily oral and maxillofacial surgery. They account for approximately 15% of all oral biopsies and predominantly affect patients in their second to fourth decades of life (1). Following the surgical enucleation of a cyst, a bony defect remains. Traditionally, the standard practice has been to allow this cavity to fill with a blood clot, relying on natural biological processes to eventually form new bone.(2) However, unassisted healing is often unpredictable. The natural healing timeline can be slow, sometimes resulting in the ingrowth of fibrous scar tissue rather than solid bone (3). More importantly, the alveolar ridge often collapses during these prolonged months of healing. This dimensional loss creates a significant rehabilitation problem, particularly if the patient requires a dental implant in the future.(4) Management of the residual dead space following jaw cyst enucleation has been highly debated, with treatment protocols evolving significantly over the past decades. Early approaches relied solely on the spontaneous organization of the blood clot; however, this often leads to soft tissue invagination and incomplete bony contouring in critical-sized defects greater than 3 cm (4,5). To provide structural support, autologous bone grafting became the historical gold standard, though its routine use is now heavily deterred by severe donor-site morbidity and increased surgical time (5). Subsequent shifts toward xenografts and human allografts reduced donor-site risks but presented new challenges, as these materials frequently exhibit unpredictable, prolonged resorption times that impede natural host bone remodeling (6). In recent years, the focus has shifted toward autologous platelet concentrates (such as PRF) and synthetic bioceramics (such as Beta-Tricalcium Phosphate). While PRF is highly osteoinductive; it lacks the mechanical rigidity necessary to prevent tissue collapse in large cystic defects (7). Conversely, bioceramics provide excellent space maintenance, but their inherent high radiopacity, severely confounds early radiographic assessment, making it difficult to distinguish residual graft particles from true new bone formation and mineralization (8). Because current modalities urge for a compromise between mechanical support, predictable resorption, and radiographic clarity; there remains a critical need for a fully radiolucent, bioactive scaffold capable of accelerating bone regeneration.(7) Metformin (1,1-dimethylbiguanide hydrochloride) is an FDA-approved, first-line oral hypoglycemic agent utilized globally for the management of Type II Diabetes Mellitus. However, extensive in vitro and in vivo studies have revealed that Metformin possesses profound, glucose-independent pleiotropic effects on bone metabolism (9). Systemic administration of Metformin has been retrospectively associated with a decreased risk of bone fractures and enhanced bone mineral density in diabetic patients (10).
At the cellular level, Metformin functions as a potent osteoinductive agent primarily through the activation of the AMP-activated protein kinase (AMPK) pathway. Activation of AMPK by Metformin subsequently upregulates the expression of Runt-related transcription factor 2 (Runx2) and Osterix which are the master transcription factors required for the differentiation of mesenchymal stem cells into mature, matrix-producing osteoblasts (9-11). Furthermore, Metformin exerts a dual action by simultaneously inhibiting osteoclastogenesis. It suppresses the Receptor Activator of Nuclear Factor Kappa-B Ligand (RANKL) expression, thereby reducing bone resorption and shifting the physiological balance toward net bone apposition (11).
In a series of randomized controlled clinical trials focused on periodontal regeneration, Pradeep et al. established that the intra-bony application of 1% Metformin gel resulted in significantly greater probing depth reduction and defect fill compared to placebo gels, confirming its clinical safety and regenerative potential in the alveolar bone (12). Montalbán et al used 1% metformin solution in an animal model of guided bone regeneration with particulate bovine hydroxyapatite and hyaluronate and the results revealed that higher average bone-biomaterial contact percentage was observed in the samples, with metformin in both the proximal and distal regions. (13) By formulating Metformin into a high-viscosity gel and injecting it directly into the surgical defect, the medication blends with the pooling blood. This approach transforms the patient's natural blood clot into an active tissue-engineering matrix. It accelerates bone regeneration and increases bone density, effectively bypassing the need for traditional physical bone grafts(14).
Despite the robust evidence supporting Metformin's osteogenic properties in periodontal intrabony defects and calvarial models, there is a notable gap in the literature regarding its application in large, post-enucleation cystic cavities of the jaws. Furthermore, previous studies frequently utilized radiopaque carriers (such as calcium phosphates) that obscure early radiographic assessment of de novo mineralization.
So the aim of this study is to evaluate the osteogenic effect of metformin gel on bone healing within cystic cavities after enucleation
| Arm | Type | Interventions | Description |
|---|---|---|---|
| Metformin Gel Group (Experimental) | Experimental | Drug: For the Experimental Arm: 1% Metformin Gel | Patients in this group will undergo surgical enucleation of their radiolucent odontogenic jaw cysts, followed by packing the residual bony cavity with an active 1% metformin gel prepared as a bioactive tissue-engineering matrix |
| Placebo Gel Group | Placebo comparator | Drug: For the Comparator / Control Arm: Placebo Gel | Patients in this group will undergo surgical enucleation of their radiolucent odontogenic jaw cysts, followed by packing the residual bony cavity with an identical placebo gel |
Sex: All, accepts healthy volunteers
Inclusion Criteria: * o Healthy adults patients . * Confirmed radiolucent odontogenic cysts requiring enucleation. * The cystic defect range 5cmto ≤15cm (19) * Good oral hygiene and strict commitment to attend follow-up scans. Exclusion Criteria: * o Medically compromised patients * Heavy smokers (consuming more than 10 cigarettes a day). * Active, acute purulent infection at the surgical site (this must be resolved before surgery).
| Facility | City | Country | Status |
|---|---|---|---|
| Fayoum University | Al Fayyum, Faiyum Governorate | Egypt |