Impact of Soft Tissue Pathophysiology in the Development and Maintenance of Bisphosphonate Related Osteonecrosis of the Jaw (BRONJ)

Ziebart, Thomas; Blatt, Sebastian; Jung, Junho; Pabst, Andreas; Halling, Frank; Heymann, Paul; Neff, Andreas; Righesso, Leonardo

doi:10.20944/preprints201610.0060.v1

Cited by 6 publications

(3 citation statements)

References 20 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Compared with the Exp + Saline group, treatment with BBG after tooth extraction effectively reduced the occurrence of BRONJ and promoted tissue healing in the extraction sockets. Recent studies indicated that soft tissue covering is a key factor for preventing BRONJ by mitigating secondary contamination and re‐establishing vascularized tissues (Ziebart et al., 2016). After BBG administration, inflammation at the injured site was reduced.…”

Section: Discussionmentioning

confidence: 99%

Borate bioactive glass prevents zoledronate‐induced osteonecrosis of the jaw by restoring osteogenesis and angiogenesis

Bai

et al. 2020

Oral Diseases

View full text Add to dashboard Cite

Objectives: Bisphosphonate-related osteonecrosis of the jaw (BRONJ) is a severe complication of systemic nitrogen-containing bisphosphonate (N-BP) administration, which leads to osteonecrosis, pain, and infection. Despite much effort, effective remedies are yet to be established. This study aimed to investigate potential recovery effect of borate bioactive glass (BBG) in vitro and in vivo. Methods: The effect of BBG on zoledronate-treated bone marrow mesenchymal cells (BMSCs) and human umbilical vein endothelial cells (HUVECs) was explored by cell counting kit-8, EdU assay, flow cytometry, alkaline phosphatase staining, alizarin red staining, angiogenesis experiment, and real-time quantitative polymerase chain reaction. The preventive effect of BBG on zoledronate-induced osteonecrosis of the jaw in rat model was examined by micro-CT, HE staining, and immunohistochemistry. Results: Exposure of BBG to BMSCs and HUVECs increased cell proliferation and restored their osteogenesis and angiogenesis potential in vitro. The BRONJ lesions were satisfactorily repaired and bone mineral density, bone volume/tissue volume, trabecula number, OCN-positive cells, and CD31-positive cells were increased in the BBG-treated groups compared with saline-treated groups. Conclusions: Exposure of BMSCs and HUVECs to BBG restores osteogenesis and angiogenesis inhibited by zoledronate. BBG successfully restores extraction socket healing of BRONJ in rat model.

show abstract

Section: Discussionmentioning

confidence: 99%

Borate bioactive glass prevents zoledronate‐induced osteonecrosis of the jaw by restoring osteogenesis and angiogenesis

Bai

et al. 2020

Oral Diseases

View full text Add to dashboard Cite

show abstract

“…Additionally, studies have suggested that BPs stimulate the production of osteoprotegerin, an osteoclast differentiation inhibitor in osteoblasts, and inhibit osteoclast differentiation 3,6) . Moreover, BPs are known to affect fibroblasts and vascular endothelial cells [7][8][9][10][11] ; however, there are few detailed studies regarding the mechanism of BPs involved in soft-tissue healing. Therefore, the effects of zoledronic acid (ZOL) on human gingival fibroblasts (HGFs) and human umbilical vein endothelial cells (HUVECs) were evaluated in this study.…”

Section: Introductionmentioning

confidence: 99%

Effects of Zoledronic Acid on Human Gingival Fibroblasts and Human Umbilical Vein Endothelial Cells

Kambara

Kobayashi

Katsuragi

et al. 2021

J. Hard Tissue Biology.

View full text Add to dashboard Cite

We evaluated the effects of zoledronic acid (ZOL) on human gingival fibroblasts (HGFs) and human umbilical vein endothelial cells (HUVECs) associated with wound healing in oral soft tissues. HGFs and HUVECs were divided into two groups: a culture media control group and a group exposed to ZOL (50 μM). Cell proliferation was measured after 2, 4, 6, and 8 days. The migration ability of cells was measured for each experiment using the wound healing assay. The apoptosis rate was confirmed using the apoptosis assay. Culture supernatants were collected from each experimental group and vascular endothelial growth factor (VEGF) production in the culture media was measured using enzyme-linked immunosorbent assay (ELISA). Further, the expression level of VEGF-A was evaluated and compared using real-time quantitative polymerase chain reaction. The proliferation and migration abilities of both HGFs and HUVECs were confirmed to be suppressed by the addition of ZOL, resulting in apoptosis. ELISA revealed that the quantity of VEGF produced in HGFs was significantly higher in the ZOL group than in the control group until 2 days after the addition of ZOL. In HGFs, the mRNA expression levels of intracellular VEGF-A increased with the addition of ZOL, demonstrating the production of VEGF. In contrast, in HUVECs, although the mRNA expression levels of endogenous VEGF-A increased with the addition of ZOL, VEGF production was considerably decreased in the culture supernatant, indicating the possibility of abnormalities in the autocrine functions of endogenous VEGF or intracellular signal transduction of exogenous VEGF. These data suggest the utility of therapeutic approaches directed toward abnormalities in VEGF intracellular signaling to improve medicationrelated osteonecrosis of the jaw soft-tissue healing.

show abstract

“…Reduced number and function of monocytes and macrophages caused by repeated administration of BPs could induce local immune dysfunction, infection, and necrosis involved in ONJ (Pazianas, 2011). In addition, as farnesyl pyrophosphate synthase (FPPS) inhibitor, nitrogen‐containing BPs especially ZOL possess worse effects on cell biology than non‐nitrogen‐containing BPs by blocking the mevalonate pathway (Ziebart et al., 2016). Considering that the macrophages RAW 264.7 can differentiate into multinucleated osteoclasts after RANKL stimulation, they are used as model of osteoclast precursors (Odkhuu et al., 2012).…”

Section: Introductionmentioning

confidence: 99%

Pharmacological evaluation of imidazole‐derived bisphosphonates on receptor activator of nuclear factor‐κB ligand‐induced osteoclast differentiation and function

et al. 2020

View full text Add to dashboard Cite

Bisphosphonates (BPs) have been commonly used in the treatment of osteolytic bone lesions, such as osteoporosis and osteogenesis imperfecta. However, serious sideeffects can occur during the therapy. To search for novel potent BPs with lower side-effects, a series of imidazole-containing BPs (zoledronic acid [ZOL]; ZOL derivatives by substitution of the hydrogen at the 2-position on the imidazole ring with a methyl [MIDP], ethyl [EIDP], n-propyl [PIDP], or n-butyl group [BIDP]) were developed and the effects on receptor activator of nuclear factor-κB ligand (RANKL)induced osteoclast differentiation were investigated using the murine macrophage RAW 264.7 cells at the protein, gene, and morphological and functional levels. Influences of these BPs on the cell growth and proliferation of RAW 264.7 were also studied in order to determine cytotoxicity. The results showed that PIDP significantly inhibited the RANKL-induced osteoclast formation in a dose-dependent fashion without inducing cytotoxicity under the concentration of 12.5 μM. It exerted remarkable suppressive effects on the development of actin rings, the bone resorption, and the expressions of osteoclastogenesis-related gene and protein markers. The down-regulation of c-Jun N-terminal kinase (JNK), protein kinase B (Akt), and inhibitor of nuclear factor kappa-B (IκB) phosphorylation in the early signaling event and subsequent inhibition of the expression of c-Fos and nuclear factor of activated T cells (NFATc1) might be involved in these effects. All these results indicated that PIDP might be a promising drug to treat bone-related disorders.

show abstract

Impact of Soft Tissue Pathophysiology in the Development and Maintenance of Bisphosphonate Related Osteonecrosis of the Jaw (BRONJ)

Cited by 6 publications

References 20 publications

Borate bioactive glass prevents zoledronate‐induced osteonecrosis of the jaw by restoring osteogenesis and angiogenesis

Borate bioactive glass prevents zoledronate‐induced osteonecrosis of the jaw by restoring osteogenesis and angiogenesis

Effects of Zoledronic Acid on Human Gingival Fibroblasts and Human Umbilical Vein Endothelial Cells

Pharmacological evaluation of imidazole‐derived bisphosphonates on receptor activator of nuclear factor‐κB ligand‐induced osteoclast differentiation and function

Contact Info

Product

Resources

About