Differential modulation of zoledronate and etidronate in osseous healing of an extracted socket and tibia defect

Lim, Shin Saeng; Lee, Beomseok; Kim, In Sook; Hwang, Soon Jung

doi:10.1016/j.oooo.2016.08.009

Cited by 16 publications

(8 citation statements)

References 35 publications

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“…The propensity of the jaws to bisphosphonate-related osteonecrosis of the jaw (BRONJ) may be due to several anatomical and physiological factors. BPs tend to be highly concentrated in the jaws rather than other skeletal sites because they preferentially deposit in bones with high turnover rates and in sites of significant remodelling [7,8].…”

Section: Introductionmentioning

confidence: 99%

“…Furthermore, unlike other skeletal sites, after surgery or trauma, the wound can be continually exposed to more than 500 different species of microorganisms, resulting in a high susceptibility to contamination and infection [11]. In normal circumstances, the healing of an open bony wound in the presence of normal oral microflora occurs without complication, although, in these cases, when oral microbes reach necrotic bone, they hinder healing [7,8]. The prevalence of BRONJ in cancer patients receiving intravenous zoledronate following tooth extraction ranges from 1.6% to 14.8% [12].…”

Section: Introductionmentioning

confidence: 99%

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Synthetic Calcium Phosphate Ceramics as a Potential Treatment for Bisphosphonate-Related Osteonecrosis of the Jaw

et al. 2019

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(1) Background: Bisphosphonate-related osteonecrosis of the jaw (BRONJ) is one of the most often seen side effects in patients treated with nitrogen-containing bisphosphonates (BPs), a post-surgical non-healing wound condition. Since calcium phosphate (CP) compounds are able to adsorb zoledronate (ZOL) when used as a drug delivery vehicle, we aimed to verify if these ceramics might have a potential protective effect for soft tissues surrounding surgical osseous wounds. (2) Methods: The chemical reaction between ZOL and CP compounds was evaluated through ultraviolet-visible spectroscopy and elemental analysis. A primary culture of human gingival fibroblasts (HGF) was established as a model to evaluate the cytotoxicity of the association of ZOL (5–500 μM) and of ZOL/biphasic calcium phosphates (BCP). Metabolic activity, cell viability, types of cell death, the cell cycle through, and the migration ability of human gingival fibroblasts were evaluated. (3) Results: ZOL was adsorbed by biphasic calcium phosphate compounds in an aqueous solution. The HGF were sensitive to ZOL toxicity; nevertheless, ZOL/BCP showed a significant protective effect regarding metabolic activity, cell viability, and cell migration. (4) Conclusions: BCP interaction with ZOL reduces or abolishes its toxicity in HGF. This finding represents a potential solution for BRONJ in the case of patients undergoing therapy with ZOL.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Synthetic Calcium Phosphate Ceramics as a Potential Treatment for Bisphosphonate-Related Osteonecrosis of the Jaw

et al. 2019

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“…To substantiate the osteogenic potential of Gel/nHAp/20 µM DM scaffold in vitro , we utilized the rat tibial bone defective model system. This system has been used in a number of studies and it has provided evidence for identifying the osteogenic potential of any biomaterials including drugs under living conditions 63–65 . Tibial bone defect model system also supports the evaluation of the regeneration potential of the scaffold at the load-bearing sites 64,65 .…”

Section: Resultsmentioning

confidence: 99%

“…This system has been used in a number of studies and it has provided evidence for identifying the osteogenic potential of any biomaterials including drugs under living conditions 63–65 . Tibial bone defect model system also supports the evaluation of the regeneration potential of the scaffold at the load-bearing sites 64,65 . Thus, a 3 mm diameter defect was created on the rat tibia using a dental burr and filled with Gel/nHAp or Gel/nHAp/20 μM DM scaffold.…”

Section: Resultsmentioning

confidence: 99%

Osteostimulatory effect of biocomposite scaffold containing phytomolecule diosmin by Integrin/FAK/ERK signaling pathway in mouse mesenchymal stem cells

Chandran

Vairamani

Selvamurugan

2019

Sci Rep

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Non-availability of an ideal alternative for autografts in treating critical-size bone defects is a major challenge in orthopedics. Phytocompounds have been proven to enhance osteogenesis via various osteogenic signaling pathways, but its decreased bioavailability and increased renal clearance limit its application. In this study, we designed a biocomposite scaffold comprising gelatin (Gel) and nanohydroxyapatite (nHAp) incorporated with diosmin (DM) and we investigated its bone forming potential in vitro and in vivo . Physiochemical characterization of the scaffold showed that DM had no effect on altering the material characteristics of the scaffold. The addition of DM enhanced the osteoblast differentiation potential of the scaffold in mouse mesenchymal stem cells at both cellular and molecular levels, possibly via the integrin-mediated activation of FAK and ERK signaling components. Using the rat tibial bone defective model, we identified the effect of DM in Gel/nHAp scaffold on enhancing bone formation in vivo . Based on our results, we suggest that Gel/nHAp/DM can be a potential therapeutic agent in scaffold-mediated bone regeneration.

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“…For the same reason, zoledronic acid is used in almost all animal studies for inducing BRONJ. 13,22,23,24 BRONJ is one of the most serious and well-known potential complications of long-term bisphosphonate therapy. 25 The treatment for BRONJ poses a challenge to oral and maxillofacial surgeons, pathologists, and oncologists.…”

Section: A B Cmentioning

confidence: 99%

Collagen sponge and rhBMP-2 improve socket healing in rats treated with zoledronic acid

Kim

2017

Braz. oral res.

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The aim of the present study was to evaluate the possible use of a commercial absorbed collagen sponge and bone morphogenetic protein (BMP) for the prevention of bisphosphonate-related osteonecrosis of the jaw (BRONJ) in rats. Twenty rats received intraperitoneal injections of 0.1-mg/kg of zoledronic acid three times a week for eight weeks before the extraction of both maxillary first molars after eight weeks. A collagen sponge (experimental group 1) and a collagen sponge with recombinant human BMP-2 (experimental group 2) were applied to the right extraction sockets of ten rats each. The 20 left extraction sockets (control groups 1 and 2) were left unprotected. After eight weeks, all rats were euthanized. Macroscopic analysis, micro-computed tomography (CT) analysis, and histological analysis were performed. There was a significant difference in the bone density between the control and experimental groups on micro-CT analysis. Impaired healing of the extraction sockets, indicating BRONJ, was observed in 80% of control group 1, 90% of control group 2, 30% of experimental group 1, and 20% of experimental group 2. The collagen sponge with/without BMP used for protecting the extraction socket had the potential for a positive effect in reducing the incidence of bisphosphonate-related osteonecrosis of the jaw in rats.

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Differential modulation of zoledronate and etidronate in osseous healing of an extracted socket and tibia defect

Cited by 16 publications

References 35 publications

Synthetic Calcium Phosphate Ceramics as a Potential Treatment for Bisphosphonate-Related Osteonecrosis of the Jaw

Synthetic Calcium Phosphate Ceramics as a Potential Treatment for Bisphosphonate-Related Osteonecrosis of the Jaw

Osteostimulatory effect of biocomposite scaffold containing phytomolecule diosmin by Integrin/FAK/ERK signaling pathway in mouse mesenchymal stem cells

Collagen sponge and rhBMP-2 improve socket healing in rats treated with zoledronic acid

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