Effects of an oral bisphosphonate and three intravenous bisphosphonates on several cell types in vitro

Jung, Junho; Park, Jung Soo; Righesso, Leonardo; Pabst, Andreas; Al‐Nawas, Bilal; Kwon, Yong‐Dae; Walter, Christian

doi:10.1007/s00784-018-2349-6

Cited by 35 publications

(42 citation statements)

References 35 publications

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“…Related studies have shown an advantage in wound healing using leukocyte enriched PRP products in a dose-dependent manner, too 46,48–51 . The use of ZA in this study led to a decrease of both osteoblasts and fibroblasts proliferations as previously proved in comparable investigations 36,52 . Interestingly, we observed a decrease in this effect on cell viability when adding PRF to ZA in both cell lines, especially in fibroblast culture.…”

Section: Discussionsupporting

confidence: 87%

Positive impact of Platelet-rich plasma and Platelet-rich fibrin on viability, migration and proliferation of osteoblasts and fibroblasts treated with zoledronic acid

Steller

Herbst

Pries

et al. 2019

Sci Rep

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Bisphosphonates are frequently used for the antiresorptive treatment in bone metastasis diseases or for osteoporosis. A side effect of this therapy is osteonecrosis of the jaw. This inhibits osteoclast function, but osteoblasts and fibroblasts are also negatively affected in terms of impaired proliferation. Additive local treatment with platelet-rich plasma (PRP) and platelet-rich fibrin (PRF) promotes adhesion, proliferation and migration of cells due to high concentrations of growth factors like PDGF, TGF and IGF. The aim of the study was to investigate the effect of PRP or PRF on proliferation, migration and viability of osteoblasts and oral fibroblasts, treated with zoledronic acid (ZA). ZA treated fibroblasts and osteoblasts were exposed to PRP/PRF. Cell proliferation, migration and viability were measured using the real-time cell-analyzer assay (RTCA), the scratch assay and the MTT assay. There was a significant increase in closure of the scratch area by PRP/PRF treated osteoblasts (PRP = 40.6%, PRF = 100.0%, NC = 0.0%) as well as fibroblasts (PRP = 100.0%, PRF = 100.0%, NC = 12.7%) in comparison to the group of negative control (all p ≤ 0 . 05 ). Furthermore, the negative effect of ZA on cell migration was generally reduced in both cell lines using PRP/PRF. The viability and proliferation of cells decreased after exposure to ZA, whereas we observed an enhancement of cell viability within 24 hours by application of PRP/PRF in ZA treated cells. The negative effect of ZA on cell proliferation was especially reduced when using PRF. The use of PRF/PRP improves the behavior of ZA-treated cells, but PRF appears to have an advantage in comparison to PRP. This study demonstrates that treatment with PRF/PRP may have positive effects in the therapy of Bisphosphonate-Related Osteonecrosis of the Jaw (BRONJ).

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Section: Discussionsupporting

confidence: 87%

Positive impact of Platelet-rich plasma and Platelet-rich fibrin on viability, migration and proliferation of osteoblasts and fibroblasts treated with zoledronic acid

Steller

Herbst

Pries

et al. 2019

Sci Rep

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“…Keratinocytes, fibroblasts and osteoblasts are the main cells that in an orchestrated way participate in the wound healing process and are among the main targets of the PRP biostimulatory action 23–28 . In contrast, studies have demonstrated that zoledronate treatment exerts negative effects on keratinocytes 37,38 , fibroblasts 39,40 and osteoblasts 41,42 . The zoledronate action on such cells has great importance in both impaired tissue repair of the tooth extraction site and occurrence of MRONJ 11–14 , which is consistent with the results obtained in this study.…”

Section: Discussionmentioning

confidence: 93%

Application of Autologous Platelet-Rich Plasma on Tooth Extraction Site Prevents Occurence of Medication-Related Osteonecrosis of the Jaws in Rats

Toro

Mello‐Neto

Santos

et al. 2019

Sci Rep

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This study evaluated the effects of local application of autologous platelet-rich plasma (PRP) on the tooth extraction site of rats presenting the main risk factors for medication-related osteonecrosis of the jaw (MRONJ). For seven weeks, senile rats were submitted to systemic treatment with vehicle (VEH and VEH-PRP) or 100 μg/Kg of zoledronate (ZOL and ZOL-PRP) every three days. After three weeks, the first lower molar was extracted. VEH-PRP and ZOL-PRP received PRP at the tooth extraction site. Euthanasia was performed at 28 days postoperatively. Clinical, histopathological, histometric and immunohistochemical analyses were carried out in histological sections from the tooth extraction site. ZOL showed lower percentage of newly formed bone tissue (NFBT), higher percentage of non-vital bone tissue (NVBT), as well as higher immunolabeling for TNFα and IL-1β. In addition, ZOL presented lower immunolabeling for PCNA, VEGF, BMP2/4, OCN and TRAP. VEH and ZOL-PRP showed improvement in the tooth extraction site wound healing and comparable percentage of NFBT, VEGF, BMP2/4 and OCN. Local application of autologous PRP proved a viable preventive therapy, which is safe and effective to restore tissue repair capacity of the tooth extraction site and prevent the occurrence of MRONJ following tooth extraction.

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“…25,34,35 In this study, using a murine osteoblast cell line (MC3T3-E1), the damaging effects caused by ZA started at 24 h and increased at 48 h. Furthermore, there was significant caspase 3/7 activation at both 24 h and 48 h after treating cells with ZA, which corroborates the already described effect on caspase 3/7 activation in human osteoblasts after ZA (up to 50 µM) treatment (72 h) (Jung et al). 10 When administrated alone, A. chica extract did not affect osteoblast viability except at 10 µg.mL −1 concentration after 48 h exposure. Some studies have reported that polyphenolic and others antioxidant compounds might react with culture medium components generating hydrogen peroxide in situ.…”

Section: Discussionmentioning

confidence: 88%

“…9 Furthermore, oral bisphosphonate presents a potency comparable to intravenous bisphosphates that compromise cell activities, reinforcing the theory that bisphosphonates detrimentally affect not only osteoclasts but also several other somatic cell types. 10 Once BRONJ occurs, there is not an established treatment for the oral lesion, and surgical excisions of the necrotic bone, systemic or topical application of antibiotics and the improvement of oral hygiene are palliative applied therapies. [11][12][13] In order to improve the healing process, many studies have focused therapeutic and cytoprotective benefits of secondary metabolites from plant origin.…”

Section: Introductionmentioning

confidence: 99%

<p>Standardized <em>Arrabidaea chica</em> Extract Shows Cytoprotective Effects in Zoledronic Acid-Treated Fibroblasts and Osteoblasts</p>

Zago¹,

Sousa²,

Servat-Medina³

et al. 2020

CCIDE

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Introduction: Osteonecrosis of the jaw is a condition associated with intraoral ulceration and bone necrosis induced by antiresorptive medications, such as zoledronic acid, a bisphosphonate. Previous data on Arrabidaea chica (H&B.) Verlot wound healing activity prompted the study reported herein on A. chica standardized hydro alcoholic extract in vitro cytoprotective activity data on epithelial and osteoblastic cells exposed to zoledronic acid (ZA). Methods: Primary human gingival fibroblasts and murine pre-osteoblasts were treated with ZA 10 µM together with 5 or 10 µg.mL −1 A. chica extract for 24h and 48 h. At both times, cells were submitted to viability assay and caspase 3/7 activation evaluation. Statistical analysis used one-way ANOVA and p=0.05. Results: In cell viability assay, a drastic damage effect of ZA appeared after 48 h in both epithelial (55.8%) and pre-osteoblastic cells (39.7%). When treated with ZA in combination with A. chica extract, cells showed higher viability values: 74.1%-82.3% for fibroblasts and 66% for pre-osteoblasts. Furthermore, the combined treatment presented lower caspase 3/7 activation in fibroblasts and pre-osteoblasts. Conclusion: At low concentrations, A. chica extract showed promising cytoprotective effects against ZA-induced damage actions; however, further in vitro and in vivo studies are required to establish the mechanism of action.

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Effects of an oral bisphosphonate and three intravenous bisphosphonates on several cell types in vitro

Cited by 35 publications

References 35 publications

Positive impact of Platelet-rich plasma and Platelet-rich fibrin on viability, migration and proliferation of osteoblasts and fibroblasts treated with zoledronic acid

Positive impact of Platelet-rich plasma and Platelet-rich fibrin on viability, migration and proliferation of osteoblasts and fibroblasts treated with zoledronic acid

Application of Autologous Platelet-Rich Plasma on Tooth Extraction Site Prevents Occurence of Medication-Related Osteonecrosis of the Jaws in Rats

<p>Standardized <em>Arrabidaea chica</em> Extract Shows Cytoprotective Effects in Zoledronic Acid-Treated Fibroblasts and Osteoblasts</p>

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