A Novel Anabolic Conjugate (C3) in the Matrix of Dicalcium Phosphate Onlay Block Grafts for Achieving Vertical Bone Augmentation: An Experimental Study on Rabbit Calvaria

Int J Oral Maxillofac Implants. 2019 July/August;34(4):e51–e63. doi: 10.11607/jomi.7236. Epub 2019 Feb 4.


Purpose: Achieving successful and predictable alveolar ridge augmentation in the vertical dimension is extremely challenging. Several materials have been investigated to achieve vertical ridge augmentation; however, the results are highly unpredictable. The collaborative team presenting this research has developed brushite- and monetite-based grafts that incorporate in their matrix a novel bone anabolic conjugate (C3) of a bisphosphonate and a potent bone-activating EP4 receptor agonist. The study objective was to investigate the potential of these graft formulations to achieve rapid, enhanced, and clinically significant bone regeneration in the vertical dimension.

Materials and methods: Brushite and monetite grafts were fabricated and characterized for phase purity, porosity, compressive strength, and microstructural morphology. They were implanted in 12 rabbit calvaria for 12 weeks. Each group (n = 6): brushite control, brushite with C3, monetite control, and monetite with C3. Postmortem samples were retrieved and processed for analysis. The percentage bone volume, vertical bone height gained, and graft resorption were calculated and assessed.

Results: The brushite and monetite grafts containing C3 integrated well onto the calvarial bone surface, with new bone extending through the graft area (36% and 80%, respectively), while the C3 lacking grafts showed decreased surface integration and bone infiltration (28% and 38%, respectively). The C3 containing brushite and monetite grafts demonstrated bone growth vertically (1.8 mm and 2.7 mm, respectively) and improved graft resorption.

Conclusion: The brushite- and monetite-based grafts loaded with the C3 conjugate resulted in greater de novo bone formation in the vertical dimension when compared with the grafts without the drug. However, the monetite grafts produced much more and predictable vertical height gain than was achieved with brushite grafts. The advantages of this new graft drug formulation in future would be to provide more predictable vertical bone regeneration, which will ultimately benefit patients undergoing dental implant placement.

MeSH terms

  • Alveolar Ridge Augmentation*
  • Animals
  • Bone Regeneration
  • Bone Transplantation
  • Calcium Phosphates*
  • Dental Implantation, Endosseous
  • Rabbits
  • Skull*


  • Calcium Phosphates