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Published in: Supportive Care in Cancer 2/2007

01-02-2007 | Original article

Prevalence of bisphosphonate associated osteonecrosis of the jaw within the field of osteonecrosis

Authors: Christian Walter, Knut A. Grötz, Martin Kunkel, Bilal Al-Nawas

Published in: Supportive Care in Cancer | Issue 2/2007

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Abstract

Objectives

Prevalence of bisphosphonate-associated osteonecrosis of the jaws within the catchment area of a university hospital maxillofacial unit and to review the outcome of treatment.

Methods

In a retrospective study, all patients with osteonecrosis, osteomyelitis and osteoradionecrosis treated in the period from January 2000 to March 2005 in the department for Maxillo Facial Surgery at the University of Mainz, Germany were analysed.

Results

Forty percent of the patients are grouped to odontogenic or surgically induced osteomyelitis. The second largest group (28%) were patients with osteoradionecrosis (ORN). Ten percent of all patients developed an osteonecrosis after treatment with bisphosphonates (BOJ). Eight percent showed osteomyelitis or sequester due to a trauma while 14% of all patients had osteomyelitis of unknown origin. All BOJ patients took bisphosphonates because of metastatic diseases of the bone (plasmocytoma, mamma carcinoma and prostate cancer) for up to 5 years. All had been administered a nitrogen-containing bisphosphonate (either pamidronat or zoledronat). Thirteen out of the 17 patients with BOJ and 14 of the 45 with ORN reported a possible trigger like previous tooth extraction, pressure denture sore or periodontal diseases.

Conclusion

These findings support the association of bisphosphonate therapy and osteonecrosis of the jaw. The importance of this new disease is characterised by the growing number of patients. The role of dental trigger factors and the poor surgical outcome both seem to justify a prophylactic dental care concept in high-risk patients.
Literature
1.
go back to reference Rogers MJ, Gordon S, Benford HL, Coxon FP, Luckman SP, Monkkonen J, Frith JC (2000) Cellular and molecular mechanisms of action of bisphosphonates. Cancer 88:2961–2978PubMedCrossRef Rogers MJ, Gordon S, Benford HL, Coxon FP, Luckman SP, Monkkonen J, Frith JC (2000) Cellular and molecular mechanisms of action of bisphosphonates. Cancer 88:2961–2978PubMedCrossRef
3.
go back to reference van der Pluijm G, Vloedgraven H, van Beek E, van der Wee-Pals L, Lowik C, Papapoulos S (1996) Bisphosphonates inhibit the adhesion of breast cancer cells to bone matrices in vitro. J Clin Invest 98:698–705PubMed van der Pluijm G, Vloedgraven H, van Beek E, van der Wee-Pals L, Lowik C, Papapoulos S (1996) Bisphosphonates inhibit the adhesion of breast cancer cells to bone matrices in vitro. J Clin Invest 98:698–705PubMed
4.
go back to reference Boissier S, Magnetto S, Frappart L, Cuzin B, Ebetino FH, Delmas PD, Clezardin P (1997) Bisphosphonates inhibit prostate and breast carcinoma cell adhesion to unmineralized and mineralized bone extracellular matrices. Cancer Res 57:3890–3894PubMed Boissier S, Magnetto S, Frappart L, Cuzin B, Ebetino FH, Delmas PD, Clezardin P (1997) Bisphosphonates inhibit prostate and breast carcinoma cell adhesion to unmineralized and mineralized bone extracellular matrices. Cancer Res 57:3890–3894PubMed
5.
go back to reference Clezardin P, Fournier P, Boissier S, Peyruchaud O (2003) In vitro and in vivo antitumor effects of bisphosphonates. Curr Med Chem 10:173–180PubMed Clezardin P, Fournier P, Boissier S, Peyruchaud O (2003) In vitro and in vivo antitumor effects of bisphosphonates. Curr Med Chem 10:173–180PubMed
6.
7.
go back to reference Perry CM, Figgitt DP (2004) Zoledronic acid: a review of its use in patients with advanced cancer. Drugs 64:1197–1211PubMedCrossRef Perry CM, Figgitt DP (2004) Zoledronic acid: a review of its use in patients with advanced cancer. Drugs 64:1197–1211PubMedCrossRef
8.
go back to reference Leyvraz S, Hess U, Flesch G, Bauer J, Hauffe S, Ford JM, Burckhardt P (1992) Pharmacokinetics of pamidronate in patients with bone metastases. J Natl Cancer Inst 84:788–792PubMedCrossRef Leyvraz S, Hess U, Flesch G, Bauer J, Hauffe S, Ford JM, Burckhardt P (1992) Pharmacokinetics of pamidronate in patients with bone metastases. J Natl Cancer Inst 84:788–792PubMedCrossRef
9.
go back to reference Amin D, Cornell SA, Gustafson SK, Needle SJ, Ullrich JW, Bilder GE, Perrone MH (1992) Bisphosphonates used for the treatment of bone disorders inhibit squalene synthase and cholesterol biosynthesis. J Lipid Res 33:1657–1663PubMed Amin D, Cornell SA, Gustafson SK, Needle SJ, Ullrich JW, Bilder GE, Perrone MH (1992) Bisphosphonates used for the treatment of bone disorders inhibit squalene synthase and cholesterol biosynthesis. J Lipid Res 33:1657–1663PubMed
10.
go back to reference Amin D, Cornell SA, Perrone MH, Bilder GE (1996) 1-Hydroxy-3-(methylpentylamino)-propylidene-1,1-bisphosphonic acid as a potent inhibitor of squalene synthase. Arzneimittelforschung 46:759–762PubMed Amin D, Cornell SA, Perrone MH, Bilder GE (1996) 1-Hydroxy-3-(methylpentylamino)-propylidene-1,1-bisphosphonic acid as a potent inhibitor of squalene synthase. Arzneimittelforschung 46:759–762PubMed
11.
go back to reference Marx RE (2003) Pamidronate (Aredia) and zoledronate (Zometa) induced avascular necrosis of jaws: a growing epidemic. J Oral Maxillofac Surg 61:1115–1117PubMedCrossRef Marx RE (2003) Pamidronate (Aredia) and zoledronate (Zometa) induced avascular necrosis of jaws: a growing epidemic. J Oral Maxillofac Surg 61:1115–1117PubMedCrossRef
12.
13.
go back to reference Migliorati CA (2003) Bisphosphanates and oral cavity avascular bone necrosis. J Clin Oncol 21:4253–4254PubMedCrossRef Migliorati CA (2003) Bisphosphanates and oral cavity avascular bone necrosis. J Clin Oncol 21:4253–4254PubMedCrossRef
14.
go back to reference Ruggiero SL, Mehrotra B, Rosenberg TJ, Engroff SL (2004) Osteonecrosis of the jaws associated with the use of bisphosphonates: a review of 63 cases. J Oral Maxillofac Surg 62:527–534PubMedCrossRef Ruggiero SL, Mehrotra B, Rosenberg TJ, Engroff SL (2004) Osteonecrosis of the jaws associated with the use of bisphosphonates: a review of 63 cases. J Oral Maxillofac Surg 62:527–534PubMedCrossRef
15.
go back to reference Grötz KA, Diel IJ (2005) Osteonekrose des Kiefers unter Bisphosphonat Langzeittherapie. Im Focus Onkologie 8:52–55 Grötz KA, Diel IJ (2005) Osteonekrose des Kiefers unter Bisphosphonat Langzeittherapie. Im Focus Onkologie 8:52–55
16.
go back to reference Fournier P, Boissier S, Filleur S, Guglielmi J, Cabon F, Colombel M, Clezardin P (2002) Bisphosphonates inhibit angiogenesis in vitro and testosterone-stimulated vascular regrowth in the ventral prostate in castrated rats. Cancer Res 62:6538–6544PubMed Fournier P, Boissier S, Filleur S, Guglielmi J, Cabon F, Colombel M, Clezardin P (2002) Bisphosphonates inhibit angiogenesis in vitro and testosterone-stimulated vascular regrowth in the ventral prostate in castrated rats. Cancer Res 62:6538–6544PubMed
17.
go back to reference Santini D, Vincenzi B, Avvisati G, Dicuonzo G, Battistoni F, Gavasci M, Salerno A, Denaro V, Tonini G (2002) Pamidronate induces modifications of circulating angiogenetic factors in cancer patients. Clin Cancer Res 8:1080–1084PubMed Santini D, Vincenzi B, Avvisati G, Dicuonzo G, Battistoni F, Gavasci M, Salerno A, Denaro V, Tonini G (2002) Pamidronate induces modifications of circulating angiogenetic factors in cancer patients. Clin Cancer Res 8:1080–1084PubMed
18.
go back to reference Wood J, Bonjean K, Ruetz S, Bellahcene A, Devy L, Foidart JM, Castronovo V, Green JR (2002) Novel antiangiogenic effects of the bisphosphonate compound zoledronic acid. J Pharmacol Exp Ther 302:1055–1061PubMedCrossRef Wood J, Bonjean K, Ruetz S, Bellahcene A, Devy L, Foidart JM, Castronovo V, Green JR (2002) Novel antiangiogenic effects of the bisphosphonate compound zoledronic acid. J Pharmacol Exp Ther 302:1055–1061PubMedCrossRef
19.
go back to reference Hughes DE, Wright KR, Uy HL, Sasaki A, Yoneda T, Roodman GD, Mundy GR, Boyce BF (1995) Bisphosphonates promote apoptosis in murine osteoclasts in vitro and in vivo. J Bone Miner Res 10:1478–1487PubMedCrossRef Hughes DE, Wright KR, Uy HL, Sasaki A, Yoneda T, Roodman GD, Mundy GR, Boyce BF (1995) Bisphosphonates promote apoptosis in murine osteoclasts in vitro and in vivo. J Bone Miner Res 10:1478–1487PubMedCrossRef
20.
go back to reference Pan B, Farrugia AN, To LB, Findlay DM, Green J, Lynch K, Zannettino AC (2004) The nitrogen-containing bisphosphonate, zoledronic acid, influences RANKL expression in human osteoblast-like cells by activating TNF-alpha converting enzyme (TACE). J Bone Miner Res 19:147–154PubMedCrossRef Pan B, Farrugia AN, To LB, Findlay DM, Green J, Lynch K, Zannettino AC (2004) The nitrogen-containing bisphosphonate, zoledronic acid, influences RANKL expression in human osteoblast-like cells by activating TNF-alpha converting enzyme (TACE). J Bone Miner Res 19:147–154PubMedCrossRef
21.
go back to reference Plotkin LI, Aguirre JI, Kousteni S, Manolagas SC, Bellido T (2005) Bisphosphonates and estrogens inhibit osteocyte apoptosis via distinct molecular mechanisms downstream of extracellular signal-regulated kinase activation. J Biol Chem 280:7317–7325PubMedCrossRef Plotkin LI, Aguirre JI, Kousteni S, Manolagas SC, Bellido T (2005) Bisphosphonates and estrogens inhibit osteocyte apoptosis via distinct molecular mechanisms downstream of extracellular signal-regulated kinase activation. J Biol Chem 280:7317–7325PubMedCrossRef
22.
go back to reference Hansen T, Kunkel M, Weber A, James Kirkpatrick C (2006) Osteonecrosis of the jaws in patients treated with bisphosphonates—histomorphologic analysis in comparison with infected osteoradionecrosis. J Oral Pathol Med 35:155–160PubMedCrossRef Hansen T, Kunkel M, Weber A, James Kirkpatrick C (2006) Osteonecrosis of the jaws in patients treated with bisphosphonates—histomorphologic analysis in comparison with infected osteoradionecrosis. J Oral Pathol Med 35:155–160PubMedCrossRef
23.
go back to reference Dearden WF (1899) Fragilitas ossium amongst workers in Lucifer match factories. BMJ 2:270CrossRef Dearden WF (1899) Fragilitas ossium amongst workers in Lucifer match factories. BMJ 2:270CrossRef
24.
go back to reference Bernardi D, Barzan L, Franchin G, Cinelli R, Balestreri L, Tirelli U, Vaccher E (2005) Treatment of head and neck cancer in elderly patients: state of the art and guidelines. Crit Rev Oncol Hematol 53:71–80PubMed Bernardi D, Barzan L, Franchin G, Cinelli R, Balestreri L, Tirelli U, Vaccher E (2005) Treatment of head and neck cancer in elderly patients: state of the art and guidelines. Crit Rev Oncol Hematol 53:71–80PubMed
25.
go back to reference Macdonald AG, Bissett JD (2001) Avascular necrosis of the femoral head in patients with prostate cancer treated with cyproterone acetate and radiotherapy. Clin Oncol (R Coll Radiol) 13:135–137 Macdonald AG, Bissett JD (2001) Avascular necrosis of the femoral head in patients with prostate cancer treated with cyproterone acetate and radiotherapy. Clin Oncol (R Coll Radiol) 13:135–137
26.
go back to reference Dawson LK, Nussey F, Oliver TB, Marks RC, Leonard RC (2001) Osteonecrosis of the femoral head following adjuvant chemotherapy for breast cancer. Breast 10:447–449PubMedCrossRef Dawson LK, Nussey F, Oliver TB, Marks RC, Leonard RC (2001) Osteonecrosis of the femoral head following adjuvant chemotherapy for breast cancer. Breast 10:447–449PubMedCrossRef
27.
go back to reference Tarassoff P, Csermak K (2003) Avascular necrosis of the jaws: risk factors in metastatic cancer patients. J Oral Maxillofac Surg 61:1238–1239PubMedCrossRef Tarassoff P, Csermak K (2003) Avascular necrosis of the jaws: risk factors in metastatic cancer patients. J Oral Maxillofac Surg 61:1238–1239PubMedCrossRef
28.
go back to reference Kluth EV, Jain PR, Stuchell RN, Frich JC Jr (1988) A study of factors contributing to the development of osteoradionecrosis of the jaws. J Prosthet Dent 59:194–201PubMedCrossRef Kluth EV, Jain PR, Stuchell RN, Frich JC Jr (1988) A study of factors contributing to the development of osteoradionecrosis of the jaws. J Prosthet Dent 59:194–201PubMedCrossRef
29.
go back to reference Curi MM, Dib LL (1997) Osteoradionecrosis of the jaws: a retrospective study of the background factors and treatment in 104 cases. J Oral Maxillofac Surg 55:540–544 (Discussion 545–546)PubMedCrossRef Curi MM, Dib LL (1997) Osteoradionecrosis of the jaws: a retrospective study of the background factors and treatment in 104 cases. J Oral Maxillofac Surg 55:540–544 (Discussion 545–546)PubMedCrossRef
30.
go back to reference Reuther T, Schuster T, Mende U, Kubler A (2003) Osteoradionecrosis of the jaws as a side effect of radiotherapy of head and neck tumour patients-a report of a thirty year retrospective review. Int J Oral Maxillofac Surg 32:289–295PubMedCrossRef Reuther T, Schuster T, Mende U, Kubler A (2003) Osteoradionecrosis of the jaws as a side effect of radiotherapy of head and neck tumour patients-a report of a thirty year retrospective review. Int J Oral Maxillofac Surg 32:289–295PubMedCrossRef
31.
go back to reference Robinson NA, Yeo JF (2004) Bisphosphonates-a word of caution. Ann Acad Med Singapore 33:48–49PubMed Robinson NA, Yeo JF (2004) Bisphosphonates-a word of caution. Ann Acad Med Singapore 33:48–49PubMed
32.
go back to reference Wagner W, Kuffner HD, Hartmann U (1986) Der bestrahlte Patient als Risikopatient bei zahnärztlich—chirurgischen Eingriffen. Dtsch Zahnarztl Z 41:440–443PubMed Wagner W, Kuffner HD, Hartmann U (1986) Der bestrahlte Patient als Risikopatient bei zahnärztlich—chirurgischen Eingriffen. Dtsch Zahnarztl Z 41:440–443PubMed
33.
go back to reference Hoskin PJ (2003) Bisphosphonates and radiation therapy for palliation of metastatic bone disease. Cancer Treat Rev 29:321–327PubMedCrossRef Hoskin PJ (2003) Bisphosphonates and radiation therapy for palliation of metastatic bone disease. Cancer Treat Rev 29:321–327PubMedCrossRef
34.
go back to reference Algur E, Macklis RM, Hafeli UO (2005) Synergistic cytotoxic effects of zoledronic acid and radiation in human prostate cancer and myeloma cell lines. Int J Radiat Oncol Biol Phys 61:535–542PubMedCrossRef Algur E, Macklis RM, Hafeli UO (2005) Synergistic cytotoxic effects of zoledronic acid and radiation in human prostate cancer and myeloma cell lines. Int J Radiat Oncol Biol Phys 61:535–542PubMedCrossRef
35.
go back to reference Schwartz HC (2004) Osteonecrosis and bisphosphonates: correlation versus causation. J Oral Maxillofac Surg 62:763–764PubMedCrossRef Schwartz HC (2004) Osteonecrosis and bisphosphonates: correlation versus causation. J Oral Maxillofac Surg 62:763–764PubMedCrossRef
Metadata
Title
Prevalence of bisphosphonate associated osteonecrosis of the jaw within the field of osteonecrosis
Authors
Christian Walter
Knut A. Grötz
Martin Kunkel
Bilal Al-Nawas
Publication date
01-02-2007
Publisher
Springer-Verlag
Published in
Supportive Care in Cancer / Issue 2/2007
Print ISSN: 0941-4355
Electronic ISSN: 1433-7339
DOI
https://doi.org/10.1007/s00520-006-0120-z

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