Significance of bisphosphonates on angiogenesis in vivo and their effect under geranyl-geraniol addition - could it alter the treatment of bisphosphonate-associated necrosis of the jaw?

Abstract

Purpose: The aim of this study was to contribute to the understanding of the inhibitory effects of bisphosphonates on tissues, with a special focus on angiogenesis. Referring to bisphosphonate-associated osteonecrosis of the jaw (BP-ONJ), it should be shown that the local addition of the isoprenoid geranyl-geraniol (GGOH) prevents vascularization processes.

Methods: A mouse model with n = 24 animals which received an injection of a collagen matrix was used. In 4 subgroups (n = 6), we examined the effect of zoledronate on the sprouting of capillary-like structures into the matrix, with and without the presence of geranyl-geraniol, as well as testing against control groups with PBS injections or collagen matrix containing PBS instead of GGOH. This was followed by a histological evaluation of the capillary-like structures.

Results: Zoledronate inhibits the sprouting of blood vessels into a collagen matrix in vivo; in the presence of GGOH this effect is significantly weakened by a factor of 3.9 (p = 0.00068).

Conclusion: This work commits to the investigation of the pathophysiology of BP-ONJ and shows a possible causal therapeutic path via the topical application of GGOH.

Keywords: Angiogenesis; Bisphosphonate-associated osteonecrosis of the jaw; Geranyl-geraniol.