Pathophysiology, risk factors and management of bisphosphonate-associated osteonecrosis of the jaw

Is there a diverse relationship of amino- and non-aminobisphosphonates?

Ingo J. Diel, Ignac Fogelman, Bilal Al-Nawas, Bodo Hoffmeister, Cesar Migliorati, Joseph Gligorov, Kalervo Väänänen, Liisa Pylkkänen, Martin Pecherstorfer, Matti S. Aapro

Research output: Contribution to journalReview article

85 Citations (Scopus)

Abstract

Reports of osteonecrosis of the jaw (ONJ) in patients receiving long-term bisphosphonate therapy have appeared in the literature since 2003. This condition involves avascular necrotic bone in the area of maxilla or mandibula and there may be a secondary infection. Most cases of ONJ have been reported in cancer patients receiving the intravenous aminobisphosphonates zoledronic acid and pamidronate monthly or q 3 week; of note these are also the two most commonly used agents of this class. Risk factors for ONJ include a history of trauma, dental surgery or dental infection and intravenous bisphosphonate administration; in addition, the extent and duration of exposure to bisphosphonates also seem to correlate with the risk. Although a direct causal relationship with bisphosphonates cannot be assumed, these agents may possibly contribute to the development of ONJ by suppression of bone remodeling in the jaw which leads to increased rates of bone mineralisation and accumulation of microfractures. Clodronate, a non-aminobisphosphonate, appears to have a different mechanism of suppressing bone remodeling compared with aminobisphosphonates, and this may explain why few cases of ONJ have been reported with clodronate despite extensive use over the past 20 years; however, the potential of clodronate to reduce the risk of ONJ while providing equivalent clinical benefit to the aminobisphosphonates needs to be substantiated in controlled clinical trials. Use of bisphosphonate therapy should be carefully planned in patients with metastatic bone disease who have risk factors for ONJ, and appropriate preventive measures taken to avoid the development of this condition.

Original languageEnglish (US)
Pages (from-to)198-207
Number of pages10
JournalCritical Reviews in Oncology/Hematology
Volume64
Issue number3
DOIs
StatePublished - Dec 1 2007

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Bisphosphonate-Associated Osteonecrosis of the Jaw
Risk Management
Osteonecrosis
Jaw
Diphosphonates
Clodronic Acid
pamidronate
zoledronic acid
Bone Remodeling
Tooth
Physiologic Calcification
Stress Fractures
Bone Diseases
Controlled Clinical Trials
Maxilla
Coinfection
Intravenous Administration
Bone and Bones

All Science Journal Classification (ASJC) codes

  • Hematology
  • Oncology

Cite this

Pathophysiology, risk factors and management of bisphosphonate-associated osteonecrosis of the jaw : Is there a diverse relationship of amino- and non-aminobisphosphonates? / Diel, Ingo J.; Fogelman, Ignac; Al-Nawas, Bilal; Hoffmeister, Bodo; Migliorati, Cesar; Gligorov, Joseph; Väänänen, Kalervo; Pylkkänen, Liisa; Pecherstorfer, Martin; Aapro, Matti S.

In: Critical Reviews in Oncology/Hematology, Vol. 64, No. 3, 01.12.2007, p. 198-207.

Research output: Contribution to journalReview article

Diel, IJ, Fogelman, I, Al-Nawas, B, Hoffmeister, B, Migliorati, C, Gligorov, J, Väänänen, K, Pylkkänen, L, Pecherstorfer, M & Aapro, MS 2007, 'Pathophysiology, risk factors and management of bisphosphonate-associated osteonecrosis of the jaw: Is there a diverse relationship of amino- and non-aminobisphosphonates?', Critical Reviews in Oncology/Hematology, vol. 64, no. 3, pp. 198-207. https://doi.org/10.1016/j.critrevonc.2007.07.005
Diel, Ingo J. ; Fogelman, Ignac ; Al-Nawas, Bilal ; Hoffmeister, Bodo ; Migliorati, Cesar ; Gligorov, Joseph ; Väänänen, Kalervo ; Pylkkänen, Liisa ; Pecherstorfer, Martin ; Aapro, Matti S. / Pathophysiology, risk factors and management of bisphosphonate-associated osteonecrosis of the jaw : Is there a diverse relationship of amino- and non-aminobisphosphonates?. In: Critical Reviews in Oncology/Hematology. 2007 ; Vol. 64, No. 3. pp. 198-207.
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AU - Al-Nawas, Bilal

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AU - Migliorati, Cesar

AU - Gligorov, Joseph

AU - Väänänen, Kalervo

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N2 - Reports of osteonecrosis of the jaw (ONJ) in patients receiving long-term bisphosphonate therapy have appeared in the literature since 2003. This condition involves avascular necrotic bone in the area of maxilla or mandibula and there may be a secondary infection. Most cases of ONJ have been reported in cancer patients receiving the intravenous aminobisphosphonates zoledronic acid and pamidronate monthly or q 3 week; of note these are also the two most commonly used agents of this class. Risk factors for ONJ include a history of trauma, dental surgery or dental infection and intravenous bisphosphonate administration; in addition, the extent and duration of exposure to bisphosphonates also seem to correlate with the risk. Although a direct causal relationship with bisphosphonates cannot be assumed, these agents may possibly contribute to the development of ONJ by suppression of bone remodeling in the jaw which leads to increased rates of bone mineralisation and accumulation of microfractures. Clodronate, a non-aminobisphosphonate, appears to have a different mechanism of suppressing bone remodeling compared with aminobisphosphonates, and this may explain why few cases of ONJ have been reported with clodronate despite extensive use over the past 20 years; however, the potential of clodronate to reduce the risk of ONJ while providing equivalent clinical benefit to the aminobisphosphonates needs to be substantiated in controlled clinical trials. Use of bisphosphonate therapy should be carefully planned in patients with metastatic bone disease who have risk factors for ONJ, and appropriate preventive measures taken to avoid the development of this condition.

AB - Reports of osteonecrosis of the jaw (ONJ) in patients receiving long-term bisphosphonate therapy have appeared in the literature since 2003. This condition involves avascular necrotic bone in the area of maxilla or mandibula and there may be a secondary infection. Most cases of ONJ have been reported in cancer patients receiving the intravenous aminobisphosphonates zoledronic acid and pamidronate monthly or q 3 week; of note these are also the two most commonly used agents of this class. Risk factors for ONJ include a history of trauma, dental surgery or dental infection and intravenous bisphosphonate administration; in addition, the extent and duration of exposure to bisphosphonates also seem to correlate with the risk. Although a direct causal relationship with bisphosphonates cannot be assumed, these agents may possibly contribute to the development of ONJ by suppression of bone remodeling in the jaw which leads to increased rates of bone mineralisation and accumulation of microfractures. Clodronate, a non-aminobisphosphonate, appears to have a different mechanism of suppressing bone remodeling compared with aminobisphosphonates, and this may explain why few cases of ONJ have been reported with clodronate despite extensive use over the past 20 years; however, the potential of clodronate to reduce the risk of ONJ while providing equivalent clinical benefit to the aminobisphosphonates needs to be substantiated in controlled clinical trials. Use of bisphosphonate therapy should be carefully planned in patients with metastatic bone disease who have risk factors for ONJ, and appropriate preventive measures taken to avoid the development of this condition.

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