Geranylgeraniol – A new potential therapeutic approach to bisphosphonate associated osteonecrosis of the jaw

Ziebart, Thomas; Koch, Felix P.; Klein, Martine; Güth, Jan‐Frederik; Adler, Julia; Pabst, Andreas; Al‐Nawas, Bilal; Walter, Christian

doi:10.1016/j.oraloncology.2010.12.003

Cited by 57 publications

(73 citation statements)

References 32 publications

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Section: Discussionmentioning

confidence: 99%

“…4,23 Recent studies have demonstrated that the decrease in geranylgeraniol production by ZA-treated cells significantly reduces cell proliferation and migration, as well as inducing cell apoptosis. 23,24 Conversely, increased cell proliferation rates have been observed for LLLT-treated cells at both energy doses selected for use in this study (0.5 and 3 J/cm 2 ), confirming that this type of therapy, at specific parameter levels, may biomodulate cell functions. [13][14][15][16][17][18]25,26 Most of the effects of LLLT have been associated with the activation of mitochondrial cytochrome c oxidase, which leads to increased adenosine triphosphate (ATP) production and the activation of several cell-signalling pathways.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Effects of low-level laser therapy on the proliferation and apoptosis of gingival fibroblasts treated with zoledronic acid

Pansani

Basso

Turirioni

et al. 2014

International Journal of Oral and Maxillofacial Surgery

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Effects of low-level laser therapy on the proliferation and apoptosis of gingival fibroblasts treated with zoledronic acid

Pansani

Basso

Turirioni

et al. 2014

International Journal of Oral and Maxillofacial Surgery

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“…According to Ziebart et al [33], the decrease of cell viability observed when cells are treated with ZA could be associated to the reduction of geranylgeraniol expression, which plays a role in the intracellular protein functions, being directly related to cell viability and migration.…”

Section: Discussionmentioning

confidence: 99%

Zoledronic Acid Inhibits Human Osteoblast Activities

et al. 2013

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Background: Bisphosphonates are potent inhibitors of bone resorption. These kinds of drugs, which are used for the treatment of osteolytic diseases, have been associated with the occurrence of oral osteonecrosis, especially in patients over 60 years old. Current studies have demonstrated that the cytotoxic effects of bisphosphonates on osteoblasts play an important role in oral osteonecrosis development. Objective: The aim of this study was to evaluate the effect of long-term application of a highly potent bisphosphonate - zoledronic acid (ZA) - on human osteoblasts in vitro. Methods: Human osteoblasts (MG63 cell line) were seeded for 72 h in wells of 24-well plates. The Dulbecco's modified Eagle's medium (DMEM) was then replaced by culture medium without fetal bovine serum (FBS), and the cells were incubated for an additional 24 h, after which ZA was added to the DMEM without FBS and incubated in contact with osteoblasts for 7, 14 or 21 days. Cell viability (CV), total protein production (TPP), alkaline phosphatase (ALP) activity, mineral nodule formation (MNF), and gene expression of ALP and osteocalcin (OCN), as well as cell morphology by scanning electronic microscopy, were evaluated. Data were statistically analyzed by Kruskal-Wallis and Mann-Whitney tests, with a significance level of 5%. Results: The cytotoxic effects of ZA on osteoblasts were characterized by reduction of CV, TPP, ALP and MNF production. In addition, ZA MNF caused a decrease in gene expression of ALP and OCN, as well as intense cell morphology alterations. All these negative effects of ZA were concentration and period dependent. Conclusion: Both concentrations of ZA (1 and 5 μM) caused cytotoxic effects to osteoblasts which reduced the production and expression of proteins that play an important role in bone matrix synthesis and mineralization.

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“…Another option is the replacement of geranylgeraniol as the production is blocked by the nitrogencontaining bisphosphonates (nBP) (Marcuzzi et al, 2011;Ziebart et al, 2011). The use of PDGF (platelet derived growth factor) in combination with a biomaterial has been tested (Adornato et al, 2007).…”

Section: Discussionmentioning

confidence: 99%

Dexrazoxane shows cytoprotective effects in zoledronic acid-treated human cells in vitro and in the rabbit tibia model in vivo

Draenert

Huetzen²,

Kämmerer

et al. 2012

Journal of Cranio-Maxillofacial Surgery

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Geranylgeraniol – A new potential therapeutic approach to bisphosphonate associated osteonecrosis of the jaw

Cited by 57 publications

References 32 publications

Effects of low-level laser therapy on the proliferation and apoptosis of gingival fibroblasts treated with zoledronic acid

Effects of low-level laser therapy on the proliferation and apoptosis of gingival fibroblasts treated with zoledronic acid

Zoledronic Acid Inhibits Human Osteoblast Activities

Dexrazoxane shows cytoprotective effects in zoledronic acid-treated human cells in vitro and in the rabbit tibia model in vivo

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