Marius Otto1,2, Julia Weigel2, Thomas Ziebart3,4, Juliana Lemound2,5. 1. Department for Pediatric Surgery, Pediatric Urology and Pediatric Orthopedics, DRK Children's Hospital Siegen, Wellersbergstrasse 60, 57072, Siegen, Germany. 2. Interdisciplinary Head & Neck Oncology Laboratory, Department for Oral and Maxillofacial Surgery, University Hospital Giessen and Marburg, Campus Marburg, 35033, Baldingerstrasse, Germany. 3. Interdisciplinary Head & Neck Oncology Laboratory, Department for Oral and Maxillofacial Surgery, University Hospital Giessen and Marburg, Campus Marburg, 35033, Baldingerstrasse, Germany. thomas.ziebart@gmx.net. 4. Clinic for Oral and Maxillofacial Surgery, DRK Hospital Alzey, Kreuznacher Str. 7-9, 55232, Alzey, Germany. thomas.ziebart@gmx.net. 5. Department of Oral and Maxillofacial-Plastic Surgery, Ruhr University of Bochum, Bochum, Germany.
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.
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.