Top

Published in:

01-02-2010 | Original Article

Bisphosphonate-associated osteonecrosis of the jaw: what do we currently know? A survey of knowledge given in the recent literature

Authors: Jan Rustemeyer, Andreas Bremerich

Published in: Clinical Oral Investigations | Issue 1/2010

Abstract

Increasing application of bisphosphonates for therapy of osteopathies has led to reports of the severe associated adverse effects of osteonecrosis of the jaw (ONJ). We reviewed recent literature to assess several aspects of bisphosphonate-associated ONJ, and to provide healthcare professionals with an overview of treatment and preventive options. Literature databases were searched using keywords. Information of 54 articles were discussed and completed by additional literature. High-risk factors were application of nitrogen-containing bisphosphonates, teeth extractions, and ill-fitting dentures. Treatment included non-surgical options and radical surgery. Success and failure were described for all treatment options; further studies investigating long-term recovery and recurrence are warranted. Paying attention to effective prevention of ONJ before, during, and after treatment is essential.

Devogelaer JP (1996) Clinical use of bisphosphonates. Curr Opin Rheumatol 8:384–391CrossRefPubMed

Tarassoff P, Csermak K (2003) Avascular necrosis of the jaws: risk factors in metastatic cancer patients. J Oral Maxillofac Surg 61:1238–1239CrossRefPubMed

Reszka AA, Rodan GA (2003) Bisphosphonate mechanism of action. Curr Rheumatol Rep 5:65–74CrossRefPubMed

Berenson JR, Hillner BE, Kyle RA, Anderson K, Lipton A, Yee GC, Biermann JS (2002) American Society of Clinical Oncology clinical practice guidelines: the role of bisphosphonates in multiple myeloma. J Clin Oncol 20:3719–3736CrossRefPubMed

Hillner BE, Ingle JN, Berenson JR, Janjan NA, Albain KS, Lipton A, Yee GC, Biermann JS, Chlebowski RT, Pfister DG (2003) American Society of Clinical Oncology 2003 update on the role of bisphosphonates and bone health issues in women with breast cancer. J Clin Oncol 21:4042–4057CrossRefPubMed

Ross JR, Saunders Y, Edmonds PM, Patel S, Broadley KE, Johnston SR (2003) Systematic review of role of bisphosphonates on skeletal morbidity in metastatic cancer. BMJ 327:469–474CrossRefPubMed

Kyrgidis A, Vahtsevanos K, Koloutsos G, Andreadis C, Boukovinas I, Teleioudis Z, Patrikidou A, Triaridis S (2008) Bisphosphonate-related osteonecrosis of the jaws: a case–control study of risk factors in breast cancer patients. J Clin Oncol 26:4634–4638CrossRefPubMed

Agarwala S, Sule A, Pai BU, Joshi VR (2002) Alendronate in the treatment of avascular necrosis of the hip. Rheumatology 41:346–347CrossRefPubMed

Astrand J, Aspenberg P (2002) Systemic alendronate prevents resorption of necrotic bone during revascularization. A bone chamber study in rats. BMC Musculoskelet Disord 3:19CrossRefPubMed

10.

Conte P, Guarneri V (2004) Safety of intravenous and oral bisphosphonates and compliance with dosing regimens. Oncologist 9:28–37CrossRefPubMed

11.

Licata AA (2005) Discovery, clinical development, and therapeutic uses of BPs. Ann Pharmacother 39:668–677CrossRefPubMed

12.

Schwartz HC (1982) Osteonecrosis of the jaws: a complication of cancer chemotherapy. Head Neck Surg 4:251–253CrossRefPubMed

13.

Jung A, Bisaz S, Fleisch H (1973) The binding of pyrophosphate and two diphosphonates by hydroxyapatite crystals. Calcif Tissue Res 11:269–280CrossRefPubMed

14.

Kasting GB, Francis MD (1992) Retention of etidronate in human, dog, and rat. J Bone Miner Res 7:513–522PubMed

15.

Khan SA, Kanis JA, Vasikaran S, Kline WF, Matuszewski BK, McCloskey EV, Beneton MN, Gertz BJ, Sciberras DG, Holland SD, Orgee J, Coombes GM, Rogers SR, Porras AG (1997) Elimination and biochemical responses to intravenous alendronate in postmenopausal osteoporosis. J Bone Miner Res 12:1700–1707CrossRefPubMed

16.

Rogers MJ, Gordon S, Benford HL, Coxon FP, Luckman SP, Monkkonen J, Frith JC (2000) Cellular and molecular mechanisms of action of bisphosphonates. Cancer 88:2961–2978CrossRefPubMed

17.

Boonekamp PM, van der Wee-Pals LJ, van Wijk-van Lennep MM, Thesing CW, Bijvoet OLM (1986) Two modes of action of bisphosphonates on osteoclastic resorption of mineralized matrix. J Bone Miner Res 1:27–39

18.

Sahni M, Guenther HL, Fleisch H, Collin P, Martin TJ (1993) Bisphosphonates act on rat bone resorption through the mediation of osteoblasts. J Clin Invest 91:2004–2011CrossRefPubMed

19.

Flanagan AM, Chambers TJ (1991) Inhibition of bone resorption by bisphosphonates: interactions between bisphosphonates, osteoclasts, and bone. Calcif Tissue Int 49:407–415CrossRefPubMed

20.

Hughes DE, Wright KR, Uy HL, Sasaki A, Yoneda T, Roodman GD, Mundy GR, Boyce BF (1005) Bisphosphonates promote apoptosis in murine osteoclasts in vitro and in vivo. J Bone Miner Res 10:1478–1487CrossRef

21.

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

22.

Allen MR, Burr DB (2008) Mandible matrix necrosis in beagle dogs after 3 years of daily oral bisphosphonate treatment. J Oral Maxillofac Surg 66:987–994CrossRefPubMed

23.

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 302:1055–1061CrossRefPubMed

24.

Santini D, Vincenzi B, Dicuonzo G, Avvisati G, Massacesi C, Battistoni F, Gavasci M, Rocci L, Tirindelli MC, Altomare V, Tocchini M, Bonsignon M, Tonini G (2003) Zoledronic acid induces significant and long-lasting modifications of circulating angiogenic factors in cancer patients. Clin Cancer Res 9:2893–2897PubMed

25.

Chirgwin JM, Mohammad KS, Guise TA (2004) Tumor-bone cellular interactions in skeletal metastases. J Musculoskelet Neuronal Interact 4:308–318PubMed

26.

Migliorati CA, Schubert MM, Peterson DE, Seneda LM (2005) Bisphosphonate-associated osteonecrosis of mandibular and maxillary bone: an emerging oral complication of supportive cancer therapy. Cancer 104:83–93CrossRefPubMed

27.

Marx RE, Sawatari Y, Fortin M, Broumand V (2005) Bisphosphonate-induced exposed bone (osteonecrosis/osteopetrosis) of the jaws: risk factors, recognition, prevention, and treatment. J Oral Maxillofac Surg 63:1567–1575CrossRefPubMed

28.

Estilo CL, Fornier M, Farooki A, Carlson D, Bohle G III, Huryn JM (2008) Osteonecrosis of the jaw related to bevacizumab. J Clin Oncol 26:4037–4043CrossRefPubMed

29.

Scavelli C, Di Pietro G, Cirulli T, Coluccia M, Boccarelli A, Giannini T, Mangialardi G, Bertieri R, Coluccia AM, Ribatti D, Dammacco F, Vacca A (2007) Zoledronic acid affects over-angiogenic phenotype of endothelial cells in patients with multiple myeloma. Mol Cancer Ther 6:3256–3262CrossRefPubMed

30.

Deckers MM, Van Beek ER, Van Der Pluijm G, Wetterwald A, Van Der Wee-Pals L, Cecchini MG, Papapoulos SE, Löwik CW (2002) Dissociation of angiogenesis and osteoclastogenesis during endochondral bone formation in neonatal mice. J Bone Miner Res 17:998–1007CrossRefPubMed

31.

Reid IR, Bolland MJ, Grey AB (2007) Is bisphosphonate-associated osteonecrosis of the jaw caused by soft tissue toxicity? Bone 41:318–320CrossRefPubMed

32.

Naidu A, Dechow PC, Spears R, Wright JM, Kessler HP, Oppermann LA (2008) The effects of bisphosponates on osteoblasts in vitro. Oral Surg Med Oral Pathol Oral Radiol Endod 106:5–13CrossRef

33.

Wang J, Goodger NM, Pogrel MA (2003) Osteonecrosis of the jaws associated with cancer chemotherapy. J Oral Maxillofac Surg 61:1104–1107CrossRefPubMed

34.

Vaidya S, Saika S, Sirohi B, Pai S, Advani S (1998) Avascular necrosis of bone—a complication of aggressive therapy for acute lymphoblastic leukemia. Acta Oncol 37:175–177CrossRefPubMed

35.

Tauchmanova L, De Rosa G, Serio B, Fazioli F, Mainolfi C, Lombardi G, Colao A, Salvatore M, Rotoli B, Selleri C (2003) Avascular necrosis in long-term survivors after allogeneic or autologous stem cell transplantation: a single center experience and a review. Cancer 97:2453–2461CrossRefPubMed

36.

Bamias A, Kastritis E, Bamia C, Moulopoulos LA, Melakopoulos I, Bozas G, Koutsoukou V, Gika D, Anagnostopoulos A, Papadimitriou C, Terpos E, Dimopouls MA (2005) Osteonecrosis of the jaw in cancer after treatment with bisphosphonates: incidence and risk factors. J Clin Oncol 23:8580–8587CrossRefPubMed

37.

Durie GM, Katz M, Crowley J (2005) Osteonecrosis of the jaw and bisphosphonates. N Engl J Med 353:99–100CrossRefPubMed

38.

Badros A, Weikel D, Salama A, Golouheva O, Schneider A, Rapoport A, Fenton R, Gahres N, Sauaville E, Ord R, Meiller T (2006) Osteonecrosis of the jaw in multiple myeloma patients: clinical features and risk factors. J Clin Oncol 24:945–952CrossRefPubMed

39.

Dimopoulos MA, Kastritis E, Anagnostopoulos A, Melakopoulos I, Gika D, Moulopoulos LA, Bamia C, Terpos E, Tsionos K, Bamias A (2006) Osteonecrosis of the jaw in patients with multiple myeloma treated with bisphosphonates: evidence of increased risk after treatment with zoledronic acid. Haematologica 91:968–971PubMed

40.

Ibrahim T, Barbanti F, Giorgio-Marrano G, Mercatali L, Ronconi S, Vincini C, Amadori D (2008) Osteonecrosis of the jaw in patients with bone metastases treated with bisphosphonates: a retrospective study. Oncologist 13:330–336CrossRefPubMed

41.

Hoff AO, Toth BB, Altundag K, Johnson MM, Warneke CL, Hu M, Nooka A, Sayegh G, Guarneri V, Desrouleaux K, Cui J, Adamus A, Gagel RF, Hortobagyi GN (2008) Frequency and risk factors associated with osteonecrosis of the jaw in cancer patients treated with intravenous bisphosphonates. J Bone Miner Res 23:826–836CrossRefPubMed

42.

Carlson ER, Basile JD (2009) The role of surgical resection in the management of bisphosphonate-related osteonecrosis of the jaws. J Oral Maxillofac Surg 67:85–95CrossRefPubMed

43.

Oizumi T, Yamaguchi K, Funayama H, Kuroishi T, Kawamura H, Sugawara S, Endo Y (2009) Necrotic actions of nitrogen-containing bisphosphonates and their inhibition by clodronate, a non-nitrogen-containing bisphosphonate in mice: potential for utilization of clodronate as a combination drug with a nitrogen-containing bisphosphonate. Basic Clin Pharmacol Toxicol 104:384–392CrossRefPubMed

44.

Van den Wyngaert T, Huizing MT, Vermorken JB (2006) Bisphosphonates and osteonecrosis of the jaw: cause and effect or a post hoc fallacy? Ann Oncol 17:1197–1204CrossRefPubMed

45.

Migliorati CA (2003) Bisphosphanates and oral cavity avascular bone necrosis. J Clin Oncol 21:4253–4254CrossRefPubMed

46.

Hoefert S, Eufinger H (2005) Osteonecrosis of the jaws as a possible adverse effect of the use of bisphosphonates. Mund Kiefer Gesichtschir 9:233–238CrossRefPubMed

47.

Marx RE (2003) Pamidronate (Aredia) and zoledronate (Zometa) induced avascular necrosis of the jaws: a growing epidemic. J Oral Maxillofac Surg 61:1115–1117CrossRefPubMed

48.

Woo SB, Hellstein JW, Kalmar JR (2006) Narrative [corrected] review: BPs and osteonecrosis of the jaws. Ann Intern Med 144:753–761PubMed

49.

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 62:527–534CrossRefPubMed

50.

Aguiar Bujanda D, Bohn Sarmiento U, Cabrera Suárez MÁ, Aguiar Morales J (2007) Assessment of renal toxicity and osteonecrosis of the jaws in patients receiving zoledronic acid for bone metastasis. Ann Oncol 18:556–560CrossRefPubMed

51.

Abu-Id MH, Warnke PH, Gottschalk J, Springer I, Wiltfang J, Acil Y, Russo PA, Kreusch T (2008) “Bis-phossy jaws”—high and low risk factors for bisphosponate-induced osteonecrosis of the jaw. J Craniomaxillofac Surg 36:95–103PubMed

52.

Markiewicz M, Maragone JE III, Campbell JH, Aguirre A (2005) Bisphosphonate-associated osteonecrosis of the jaws. A review of current knowledge. J Am Dent Assoc 12:1669–1674

53.

Weitzman R, Sauter N, Eriksen EF, Tarassoff PG, Lacerna LV, Dias R, Altmeyer A, Csermak-Renner K, McGrath L, Lantwicki L, Hohneker JA (2007) Critical review: updated recommendations for the prevention, diagnosis, and treatment of osteonecrosis of the jaw in cancer patients—May 2006. Crit Rev Oncol Hematol 62:148–152CrossRefPubMed

54.

Hellstein JW, Marek CL (2005) Bisphosphonate osteochemonecrosis (bis-phossy jaw): is this phossy jaw of the 21st century? J Oral Maxillofac Surg 63:682–689CrossRefPubMed

55.

Marx RE (2009) Reconstruction of defects caused by bisphosphonate-induced osteonecrosis of the jaws. J Oral Maxillofac Surg 67:107–119CrossRefPubMed

56.

Migliorati CA, Armonis BN, Nicolatou-Galitis O (2008) Oral osteonecrosis associated with the use of ibandronate: report of a case and clinical implications. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 106:e18–e21CrossRefPubMed

57.

Black DM, Schwartz AV, Ensrud KE, Cauley JA, Levis S, Quandt SA, Satterfield S, Wallace RB, Bauer DC, Palermo L, Wehren LE, Lombardi A, Santora AC, Cummings SR (2006) Effects of continuing or stopping alendronate after 5 years of treatment: the Fracture Intervention Trial Long-term Extension (FLEX): a randomized trial. JAMA 296:2927–2938CrossRefPubMed

58.

Polizzotto MN, Cousins V, Schwarer AP (2006) BP-associated osteonecrosis of the auditory canal. Br J Haematol 132:114CrossRefPubMed

59.

Advisory Task Force on Bisphosphonate-Related Ostenonecrosis of the Jaws (2007) American Association of Oral and Maxillofacial Surgeons position paper on bisphosphonate-related osteonecrosis of the jaws. J Oral Maxillofac Surg 65:369–376CrossRef

60.

Berenson JR (2005) Recommendations for zoledronic acid treatment of patients with bone metastases. Oncologist 10:52–62CrossRefPubMed

61.

Migliorati CA (2005) Bisphosphonate-associated oral osteonecrosis. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 99:135CrossRefPubMed

62.

Ponte-Fernández N, Estefania-Fresco R, Aguirre-Urizar JM (2006) Bisphosphonates and oral pathology I. General and preventive aspects. Med Oral Patol Oral Cir Bucal 11:396–400

63.

Ruggiero SL, Fantasia J, Carlson E (2006) BP-related osteonecrosis of the jaw: background and guidelines for diagnosis, staging and management. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 102:433–441CrossRefPubMed

64.

Kumar SKS, Meru MC, Sedghizadeh PP (2008) Osteonecrosis of the jaws secondary to bisphosphonate therapy: a case series. J Contemp Dent Pract 1:63–69

Title: Bisphosphonate-associated osteonecrosis of the jaw: what do we currently know? A survey of knowledge given in the recent literature
Authors: Jan Rustemeyer
Andreas Bremerich
Publication date: 01-02-2010
Publisher: Springer-Verlag
Published in: Clinical Oral Investigations / Issue 1/2010
Print ISSN: 1432-6981
Electronic ISSN: 1436-3771
DOI: https://doi.org/10.1007/s00784-009-0294-0

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Bisphosphonate-associated osteonecrosis of the jaw: what do we currently know? A survey of knowledge given in the recent literature

Abstract

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 1/2010

Undesirable and adverse effects of tooth-whitening products: a review

A novel sustained-release clotrimazole varnish for local treatment of oral candidiasis

Swine-origin H1N1 influenza A virus and dental practice: a critical review

The efficacy of a paste containing Myrtus communis (Myrtle) in the management of recurrent aphthous stomatitis: a randomized controlled trial

Effects of mouthrinses containing essential oils and alcohol-free chlorhexidine on human plaque acidogenicity

Bisphosphonate-related osteonecrosis of the jaw: clinical correlations with computerized tomography presentation