In vitro cytotoxicity of zoledronate (nitrogen-containing bisphosphonate: NBP) and/or etidronate (non-NBP) in tumour cells and periodontal cells

PRGF exerts a cytoprotective role in zoledronic acid-treated oral cells

“…Zoledronic acid is the most potent intravenous N-BP used to prevent bone loss in patients with bone dysfunction, with the osteonecrosis of the jaw (ONJ) as one of its main serious adverse effects [2]. The release of N-BPs accumulated in the jaws may also damage the surrounding oral soft tissues, reflecting that BRONJ pathology occurs via bone and soft tissue mechanism [6,23]. The in vitro results presented herein show that ZA exerts a dose-dependent cytotoxic effect on proliferation and survival of human primary gingival fibroblasts and alveolar osteoblasts ( Figs.…”

“…BPs are administered either intravenously (IV) (mainly pamidronate and zoledronic acid) or orally (alendronate and risedronate among others) [5]. Zoledronic acid (ZA) is one of the most frequently used and potent intravenously nitrogencontaining bisphosphonates [5,6].…”

Inflammatory Effects of Nitrogen-Containing Bisphosphonates (N-BPs): Modulation by Non-N-BPs

“…Indeed, N-BPs are cytotoxic not only to osteoclasts, but also to various other cell-types. 7) However, it is poorly understood how N-BPs enter cells at a neutral pH. We previously found in mice that the non-cyclic non-N-BPs etidronate (Eti, used in Japan) and clodronate (Clo, not used in Japan) can reduce or prevent the inflammatory side effects of both the non-cyclic N-BP alendronate (Ale) and the cyclic N-BPs zoledronate (Zol) and minodronate (Min).…”

Underlying Mechanisms and Therapeutic Strategies for Bisphosphonate-Related Osteonecrosis of the Jaw (BRONJ)

“…In addition, the pathway for cholesterol synthesis generally resides in all eukaryotic cells. Indeed, N-BPs exhibit cytotoxicity in vitro not only against osteoclasts but also against a variety of other cells 48) and Zol has been reported to augment the cytotoxic effect of TNF against vascular endothelial cells. 49,50) As described in Section 4.1., N-BPs induce HDC in various tissues in mice and also augment HDC-induction by LPS, and vascular endothelial cells are supposed to be the major cells in which HDC is induced.…”

“…In contrast, Eti was not toxic at 1-100 mM in any of the cells tested, and Eti reduced the cytotoxicity of Zol in many cell-types. 48) …”