Nationwide Survey for Bisphosphonate-Related Osteonecrosis of the Jaws in Japan

Urade, Masahiro; Tanaka, Noriaki; Furusawa, Kiyofumi; Shimada, Jun; Shibata, Takanori; Kirita, Tadaaki; Yamamoto, Tetsuya; Ikebe, Tetsuro; Kitagawa, Yoshimasa; Fukuta, Jinichi

doi:10.1016/j.joms.2011.03.051

Cited by 100 publications

(65 citation statements)

References 27 publications

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“…5) Notably, the ratio of the number of BRONJ cases among osteoporotic patients receiving oral N-BPs to that in patients receiving intravenous N-BPs is higher in Japan than in the U.S.A. and EU. 6) The cytotoxicity of N-BPs has been shown to be due to the intracellular inhibition of farnesyl pyrophosphate synthase (FPPS) in the pathway of cholesterol synthesis.…”

mentioning

confidence: 99%

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

Shima

Tsuchiya

Oizumi

et al. 2017

Biological & Pharmaceutical Bulletin

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confidence: 99%

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

Shima

Tsuchiya

Oizumi

et al. 2017

Biological & Pharmaceutical Bulletin

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“…Il n'existe cependant aucun consensus international. Toutefois, plusieurs articles récents montrent des taux plus élevés de « guérison » des ostéonécroses après traitement chirurgical qu'après traitement conservateur, même dans les stades précoces de déve-loppement pour lesquels les thérapeutiques interventionnistes ont été longtemps déconseillées [19][20][21][22]. Certains auteurs évoquent des traitements complémentaires comme l'oxygéno-thérapie hyperbare [23] mais son efficacité n'est pas prouvée.…”

Section: Discussionunclassified

Ostéonécrose des maxillaires : quand l’ancien traitement avec bisphosphonates est méconnu

Renoux

Folliguet

Nguyen

et al. 2014

Med Buccale Chir Buccale

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Résumé -Introduction :La personne âgée est atteinte de polypathologies et polymédiquée. Les prescriptions sont faites par plusieurs médecins qui s'ignorent réciproquement, ce qui augmente le risque d'effets adverses. Observation : Le cas d'une patiente de 91 ans vivant dans un établissement d'hébergement pour personnes âgées dépendantes est rapporté. Quatre mois après une perfusion de zolédronate suite à une chute avec tassement vertébral, elle a consulté pour une gêne maxillaire gauche, ce qui a permis de découvrir un foyer d'ostéonécrose spontanée maxillaire. Un deuxième foyer d'ostéonécrose, mandibulaire, a été diagnostiqué trois semaines plus tard. Considérant l'âge de la patiente et l'absence de troubles fonctionnels, seul un débridement chirurgical superficiel a été réalisé. Discussion : L'apparition d'ostéonécroses spontanées bimaxillaires quatre mois après une perfusion unique de zolédronate étant peu probable, la recherche approfondie des antécédents de la patiente a permis de retrouver une prise de trois bisphosphonates oraux pendant sept ans sans aucun examen et suivi bucco-dentaire. L'interrogatoire médical des patients âgés atteints de troubles cognitifs étant difficile, la recherche de tous les médecins prescripteurs est nécessaire. Conclusion : La prise en charge de l'ostéonécrose associée aux bisphosphonates étant complexe, le chirurgien-dentiste joue un rôle important dans la prévention de cette pathologie.Abstract -Osteonecrosis of the jaws: when past bisphosphonates therapy is unknown. Introduction: Older people have multiple morbidities and are polymedicated. The medicines are prescribed by several doctors who are unaware of each other, hence the increased risk of adverse effects. Observation: We report the case of an institutionalized 91-year-old female patient. Following a fall resulting in a vertebral compression fracture, she received an infusion of zoledronic acid. Four months after this treatment, she consulted for left maxillary discomfort. A voluminous bone sequestrum revealed a maxillary osteonecrosis area. Right mandibular osteonecrosis was diagnosed three weeks later. Considering the patient's age and the lack of functional impairment, surgical debridement was the only procedure performed. Discussion: The emergence of spontaneous maxillary osteonecrosis four months after a single infusion of bisphosphonate being implausible, we searched her medical records for the physicians who treated the patient before her institutionalization. We found three oral bisphosphonate medications during seven years. No oral examination was performed during this therapy. The diagnosis of jaw osteonecrosis should lead the oral surgeon to look for past bisphosphonate therapy among other possible etiologies of this pathology. Indeed, this treatment is often forgotten by patients suffering from cognitive impairment. Conclusion: As the management of bisphosphonate-related osteonecrosis of the jaws is difficult, the oral surgeon has an important role in the prevention of this pathology. Mots clés :bisphospho...

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“…However, in recent years, serious adverse effects have been viewed with suspicion, and bisphosphonate-related osteonecrosis of the jaws (BRONJ) is an issue of particular concern. The majority of reported cases of bisphosphonate osteonecrosis have been subsequent to dental extractions, intraoral surgical intervention or mucosal trauma (15)(16)(17)(18). BRONJ adversely affects quality of life, producing significant morbidity in afflicted patients (19), and at present, the action mechanism of bisphosphonates is unclear, and their effects on osteoclasts remain evasive.…”

Section: Discussionmentioning

confidence: 99%

Effects of bisphosphonates on osteoclastogenesis in RAW264.7 cells

Yoshimura

2012

Int J Mol Med

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Abstract.Bisphosphonates are used as therapeutic agents for the management of osteoporosis and other bone diseases. However, the precise effects and mechanisms of bisphosphonates on osteoclastogenesis are unclear, as previous studies have reported contradictory findings and no studies have circumstantially assessed the effects of bisphosphonates on osteoclastogenesis. Therefore, the aim of this study was to determine the effects of bisphosphonates on osteoclastogenesis in RAW264.7 (RAW) cells. To examine the direct effects of bisphosphonates on osteoclast differentiation via receptor activator of nuclear factor-κB (RANK) ligand (RANKL), RAW cells were cultured with bisphosphonates. Addition of bisphosphonates to RAW cells led to a significant decrease in the number of osteoclasts and large osteoclasts (≥8 nuclei) in a bisphosphonate concentration-dependent and time-dependent manner. The cytotoxicity of non-nitrogen-containing bisphosphonates was specific to osteoclasts, while nitrogen-containing bisphosphonates were cytotoxic and induced cell death in both osteoclasts and RAW cells. Resorption activity was significantly diminished by treatment with bisphosphonates, thus confirming that bisphosphonates impair the absorptive activity of osteoclasts. We also investigated the effects of bisphosphonates on the mRNA expression of genes associated with osteoclastogenesis, osteoclast-specific markers and apoptosis-related genes using quantitative real-time PCR. The results suggest that bisphosphonates suppress osteoclast differentiation and infusion, and induce osteoclast apoptosis. With regard to osteoclast apoptosis induced by bisphosphonates, we further investigated the detection of DNA fragmentation and Caspase-Glo 3/7 assay. DNA fragmentation was confirmed after treatment with bisphosphonates, while caspase-3/7 activity increased significantly when compared with controls. In conclusion, bisphosphonates directly inhibited RANKLstimulated osteoclast differentiation and fusion in RAW cells. It was confirmed that bisphosphonates impair osteoclast resorption activity and induce apoptosis. The effects of nonnitrogen-containing bisphosphonates were also specific to osteoclasts, while nitrogen-containing bisphosphonates were cytotoxic and induced cell death in both osteoclasts and RAW cells.

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Nationwide Survey for Bisphosphonate-Related Osteonecrosis of the Jaws in Japan

Cited by 100 publications

References 27 publications

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

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

Ostéonécrose des maxillaires : quand l’ancien traitement avec bisphosphonates est méconnu

Effects of bisphosphonates on osteoclastogenesis in RAW264.7 cells

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