Denosumab and bisphosphonates : Different mechanisms of action and effects

  • Baron R
  • Ferrari S
  • Russell R
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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.|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.|All bisphosphonates induced a statistically significant decrease of MVD (p each

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  • Roland Baron

  • Serge Ferrari

  • R Graham G Russell

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