Suppression of osteoclastogenesis signalling pathways and attenuation of ameloblastic osteolysis induced by local administration of CaP-bisphosphonate and CaP-doxycycline cements: Review of the literature and therapeutic hypothesis

Abstract

Background: It may seem incredible, even unimaginable, that some issues have not been properly studied and explained in the literature. One of these issues is the non-surgical treatment of osteolytic tumors of the jaws, especially ameloblastoma. Main text: This tumour invades the jaw through a mechanism of resorption of the surrounding bone. Osteoclasts are known to initiate physiological bone remodelling during bone growth, tooth eruption and fracture healing. They are also able to mediate bone loss in pathological conditions such as ameloblastoma. Therefore, inhibition of osteoclasts would be a potential target for the treatment of ameloblastoma.To date, the mechanisms of bone resorption in ameloblastoma are associated with the expression of receptor activator of nuclear factor kappa B ligand (RANKL) and matrix metalloproteinases 2 and 9.However, in terms of therapeutic applications of this approach, bisphosphonates have been shown to inhibit the proliferation and differentiation of osteoclast precursors through the inactivation of molecular signalling pathways involving M-CSF and RANKL. The same is true for doxycycline, which inhibits the activity of mammalian collagenases and gelatinases, an activity unrelated to its antimicrobial efficacy. Conclusion: this review, we report on the current state of knowledge on the involvement of osteoclastogenesis in the pathogenesis of ameloblastoma. We also present possible clinical applications of a calcium phosphate cement-based local delivery device for bisphosphonates and doxycycline as a potential treatment for ameloblastoma of the jaws.

Keywords

• Ameloblastoma
• Bone resorption
• Bisphosphonate
• Doxycycline
• RANKL