Antiresorptive agent-related osteonecrosis of the jaw: Position Paper 2017 of the Japanese Allied Committee on Osteonecrosis of the Jaw

Yoneda, Toshiyuki; Hagino, Hiroshi; Sugimoto, Toshitsugu; Ohta, Hiroaki; Takahashi, Shunji; Soen, Satoshi; Taguchi, Akira; Nagata, Toshihiko; Urade, Masahiro; Shibahara, Takahiko; Toyosawa, Satoru

doi:10.1007/s00774-016-0810-7

Cited by 243 publications

(333 citation statements)

References 54 publications

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“…25 Many hypotheses regarding the pathogenesis of BRONJ -including toxicity to the oral epithelium, altered wound healing, high turnover of the bone cells of the jaw, oral biofilm formation, infection and inflammation, antiangiogenesis, suppression of bone turnover, changes in immune surveillance, and osteoblast death -have been proposed. 6,16,21,26 Its etiopathogenesis is multifactorial, 27 and decreased bone turnover, antiangiogenic effects, and infection are the main hypotheses suggested for the pathogenesis of BRONJ to date. 6,28 Injury to the alveolar bone, such as tooth extraction, induces the release of bisphosphonates and disrupts epithelial healing.…”

Section: A B Cmentioning

confidence: 99%

“…6,16,21,26 Its etiopathogenesis is multifactorial, 27 and decreased bone turnover, antiangiogenic effects, and infection are the main hypotheses suggested for the pathogenesis of BRONJ to date. 6,28 Injury to the alveolar bone, such as tooth extraction, induces the release of bisphosphonates and disrupts epithelial healing. 7 Despite numerous efforts to develop experimental studies, the etiology and pathophysiology of BRONJ remain largely unclear.…”

Section: A B Cmentioning

confidence: 99%

“…3 Therefore, pre-clinical animal studies are urgently needed to establish the treatment of and preventive strategies for BRONJ. 3,5,6 Clinical studies on the prevention of BRONJ have been conducted. 29,30 Bermúdez-Bejarano et al 30 reported, by a review of clinical articles, that antibiotic prophylaxis prior to oral surgery was important in avoiding osteonecrosis and promoting proper healing, since the exposure of the bone in the oral cavity led to bacterial colonization of the modified bone after tooth extraction.…”

Section: A B Cmentioning

confidence: 99%

“…4,5 Osteonecrosis of the jaw associated with antiresorptive agents has also been named antiresorptive agent-related osteonecrosis of the jaw (ARONJ). 6 There is Declaration of Interests: The authors certify that they have no commercial or associative interest that represents a conflict of interest in connection with the manuscript.…”

Section: Introductionmentioning

confidence: 99%

“…1 Moreover, the Japanese Allied Committee reported that an understanding of the effects of antiresorptive agents at a cellular level was needed, and that these agents play a critical role in the closure of tooth extraction sockets to protect the alveolar bone from exposure to the oral cavity. 6 Various animal studies have been reported recently, 9,14,17,18 but few studies on the prevention methods for MRONJ have been conducted in animal models. The authors attempted to address two questions, based on the collagen sponge, which has been commonly used for socket preservation, and bone morphogenetic protein (BMP), which has been very effective for bone regeneration in the clinic: Does closure of the extraction socket with a collagen sponge have a positive effect on the prevention of alveolar bone exposure?…”

Section: Introductionmentioning

confidence: 99%

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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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Section: A B Cmentioning

confidence: 99%

Section: A B Cmentioning

confidence: 99%

Section: A B Cmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

Kim

2017

Braz. oral res.

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A small‐molecule PAI‐1 inhibitor prevents bone loss by stimulating bone formation in a murine estrogen deficiency‐induced osteoporosis model

et al. 2018

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Osteoporosis is a progressive bone disease caused by an imbalance between bone resorption and formation. Recently, plasminogen activator inhibitor‐1 (PAI‐1) was shown to play an important role in bone metabolism using PAI‐1‐deficient mice. In this study, we evaluated the therapeutic benefits of novel, orally available small‐molecule PAI‐1 inhibitor (iPAI‐1) in an estrogen deficiency‐induced osteoporosis model. Eight‐week‐old C57BL/6J female mice were divided into three groups: a sham + vehicle (Sham), ovariectomy + vehicle (OVX + v), and OVX + iPAI‐1 (OVX + i) group. iPAI‐1 was administered orally each day for 6 weeks starting the day after the operation. Six weeks of iPAI‐1 treatment prevented OVX‐induced trabecular bone loss in both the femoral bone and lumbar spine. Bone formation activity was significantly higher in the OVX + i group than in the OVX + v and Sham groups. Unexpectedly, OVX‐induced osteoclastogenesis was partially, but significantly reduced. Fluorescence‐activated cell sorting analyses indicated that the number of bone marrow stromal cells was higher in the OVX + i group than that in the OVX + v group. A colony‐forming unit‐osteoblast assay indicated enhanced mineralized nodule formation activity in bone marrow cells isolated from iPAI‐1‐treated animals. Bone marrow ablation analysis indicated that the remodeled trabecular bone volume was significantly higher in the iPAI‐1‐treated group than that in the control group. In conclusion, our results suggest PAI‐1 blockade via a small‐molecule inhibitor is a new therapeutic approach for the anabolic treatment of postmenopausal osteoporosis.

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Intraoral localized methotrexate‐associated lymphoproliferative disorders concurrent with antiresorptive agent‐related osteonecrosis of the jaw: A case report and literature review

Minabe

Suzuki

Komatsu

et al. 2020

Clinical Case Reports

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Antiresorptive agent-related osteonecrosis of the jaw: Position Paper 2017 of the Japanese Allied Committee on Osteonecrosis of the Jaw

Cited by 243 publications

References 54 publications

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

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

A small‐molecule PAI‐1 inhibitor prevents bone loss by stimulating bone formation in a murine estrogen deficiency‐induced osteoporosis model

Intraoral localized methotrexate‐associated lymphoproliferative disorders concurrent with antiresorptive agent‐related osteonecrosis of the jaw: A case report and literature review

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