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Clinical Oral Investigations

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01-04-2014 | Original Article

Bisphosphonates’ antiangiogenic potency in the development of bisphosphonate-associated osteonecrosis of the jaws: influence on microvessel sprouting in an in vivo 3D Matrigel assay

Authors: A. M. Pabst, T. Ziebart, M. Ackermann, M. A. Konerding, C. Walter

Published in: Clinical Oral Investigations | Issue 3/2014

Abstract

Objectives

Bisphosphonate-associated osteonecrosis of the jaw (BP-ONJ) is an adverse side effect of long-term bisphosphonate treatment. One theory of BP-ONJ etiology suggests a negative influence of these agents on angiogenesis and vascularization. This in vivo study analyzed the effects of bisphosphonates on angiogenesis in a 3D Matrigel assay.

Materials and methods

Matrigel plugs were implanted into fifty 6–8-week-old female nude mice. Ten animals each were treated either with clodronate, ibandronate, pamidronate, zoledronate, or carrier solution as controls. The microvessel density (MVD), microvessel area (MVA), and microvessel size (MVS) in Matrigel plugs were analyzed after 21 days of treatment by immunohistochemistry and exemplary 3D microvascular corrosion castings.

Results

All bisphosphonates induced a statistically significant decrease of MVD (p each <0.001), whereby the nitrogen-containing bisphosphonates (N-BPs) demonstrated a clearly stronger effect than non-nitrogen-containing bisphosphonates (NN-BP) clodronate (control 166, clodronate 99, ibandronate 48, pamidronate 47, zoledronate 35 microvessels/mm²). Referring to MVA, similar results could be detected. MVS was significantly increased especially by ibandronate (103 %) compared to control group (p < 0.001). Scanning electron microscope scans of the corrosion castings confirmed these results.

Conclusions

The stronger influence on MVD by N-BPs compared to the NN-BP clodronate may explain for the lack of BP-ONJ after treatment with NN-BPs.

Clinical relevance

Ibandronate induced a strong increase of MVS. In combination with the reduced MVD, this could result only in a fractional reduced perfusion which might be an explanation for the lower occurrence of BP-ONJ in patients receiving ibandronate compared to patients receiving pamidronate or zoledronate.

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Title: Bisphosphonates’ antiangiogenic potency in the development of bisphosphonate-associated osteonecrosis of the jaws: influence on microvessel sprouting in an in vivo 3D Matrigel assay
Authors: A. M. Pabst
T. Ziebart
M. Ackermann
M. A. Konerding
C. Walter
Publication date: 01-04-2014
Publisher: Springer Berlin Heidelberg
Published in: Clinical Oral Investigations / Issue 3/2014
Print ISSN: 1432-6981
Electronic ISSN: 1436-3771
DOI: https://doi.org/10.1007/s00784-013-1060-x

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Bisphosphonates’ antiangiogenic potency in the development of bisphosphonate-associated osteonecrosis of the jaws: influence on microvessel sprouting in an in vivo 3D Matrigel assay

Abstract

Objectives

Materials and methods

Results

Conclusions

Clinical relevance

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Objectives

Materials and methods

Results

Conclusions

Clinical relevance

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