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Bisphosphonates and Dental Implant Treatment

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Oral and Cranial Implants

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Abstract

Bisphosphonates (BP) are synthetic pyrophosphates possessing a strong affinity to calcium and magnesium ions as well as biologically generated hydroxyapatite. The first successful chemical synthesis of 1-hydroxy-1,1-ethylidene bisphosphonate disodium salt (etidronate) was reported by Von Baeyer and Hoffmann in 1897 (Francis and Valent 2007). However, BPs had no known uses until the first experimental application in dentistry. Then, in the 1960s, calcium-chelating agents were actively examined for possible efficacy in removing dental calculus; however, many of these agents not only removed calculus but also etched enamel and caused damage. When etidronate was tested, the highly polished enamel surface was not damaged (Briner and Francis 1973). This observation has inspired further studies about the adsorption of BPs onto hydroxyapatite surfaces.

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References

  • Abu-Id MH, Warnke PH, Gottschalk J, Springer I, Wiltfang J, Acil Y et al (2008) ‘Bis-phossy jaws’ – high and low risk factors for bisphosphonate-induced osteonecrosis of the jaw. J Craniomaxillofac Surg 36(2):95–103

    Article  PubMed  Google Scholar 

  • Aghaloo TL, Kang B, Sung EC, Shoff M, Ronconi M, Gotcher JE et al (2011) Periodontal disease and bisphosphonates induce osteonecrosis of the jaws in the rat. J Bone Miner Res 26(8):1871–1882

    Article  PubMed  Google Scholar 

  • Almubarak H, Jones A, Chaisuparat R, Zhang M, Meiller TF, Scheper MA (2011) Zoledronic acid directly ­suppresses cell proliferation and induces apoptosis in highly tumorigenic prostate and breast cancers. J Carcinog 10:2

    Article  PubMed  Google Scholar 

  • Altman RD, Johnston CC, Khairi MR, Wellman H, Serafini AN, Sankey RR (1973) Influence of disodium etidronate on clinical and laboratory manifestations of Paget’s disease of bone (osteitis deformans). N Eng J Med 289(26):1379–1384

    Article  Google Scholar 

  • Bassett CA, Donath A, Macagno F, Preisig R, Fleisch H, Francis MD (1969) Diphosphonates in the treatment of myositis ossificans. Lancet 2(7625):845

    Article  PubMed  Google Scholar 

  • Bedogni A, Blandamura S, Lokmic Z, Palumbo C, Ragazzo M, Ferrari F et al (2008) Bisphosphonate-associated jawbone osteonecrosis: a correlation between imaging techniques and histopathology. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 105(3):358–364

    Article  PubMed  Google Scholar 

  • Bedogni A, Bettini G, Totola A, Saia G, Nocini PF (2010) Oral bisphosphonate-associated osteonecrosis of the jaw after implant surgery: a case report and literature review. J Oral Maxillofac Surg 68(7):1662–1666

    Article  PubMed  Google Scholar 

  • Body JJ, Lortholary A, Romieu G, Vigeneron AM, Ford J (1999) A dose-finding study of zoledronate in hypercalcemic cancer patients. J Bone Min Res 14(9):1557–1561

    Article  Google Scholar 

  • Briner WW, Francis MD (1973) In vitro and in vivo evaluation of anti-calculus agents. Calcif Tissue Res 11(1):10–22

    Article  PubMed  Google Scholar 

  • Brooks JK, Gilson AJ, Sindler AJ, Ashman SG, Schwartz KG, Nikitakis NG (2007) Osteonecrosis of the jaws associated with use of Risedronate: report of 2 new cases. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 103(6):780–786

    Article  PubMed  Google Scholar 

  • Carini F, Saggese V, Porcaro G, Barbano L, Baldoni M (2012) Surgical protocol in patients at risk for bisphosphonate osteonecrosis of the jaws: clinical use of serum telopetide CTX in preventive monitoring of surgical risk. Ann Stomatol (Roma) 3(1):31–36

    Google Scholar 

  • Conte-Neto N, Bastos AS, Spolidorio LC, Marcantonio RA, Marcantonio E Jr (2011) Oral bisphosphonate-related osteonecrosis of the jaws in rheumatoid arthritis patients: a critical discussion and two case reports. Head Face Med 7:7 doi: 10.1186/1746-160X-7-7

  • Edwards BJ, Hellstein JW, Jacobsen PL, Kaltman S, Mariotti A, Migliorati CA (2008) Updated recommendations for managing the care of patients receiving oral bisphosphonate therapy: an advisory statement from the American Dental Association Council on Scientific Affairs. J Am Dent Assoc 139(12):1674–1677

    PubMed  Google Scholar 

  • Eekman DA, Bultink IE, Heijboer AC, Dijkmans BA, Lems WF (2011) Bone turnover is adequately suppressed in osteoporotic patients treated with bisphosphonates in daily practice. BMC Musculoskelet Disord 12:167 doi:10.1186/1471-2474-12-167

    Article  PubMed  Google Scholar 

  • Favia G, Piattelli A, Sportelli P, Capodiferro S, Iezzi G (2011) Osteonecrosis of the posterior mandible after implant insertion: a clinical and histological case report. Clin Implant Dent Relat Res 13(1):58–63

    Article  PubMed  Google Scholar 

  • Fedele S, Porter SR, D’Aiuto F, Aljohani S, Vescovi P, Manfredi M et al (2010) Nonexposed variant of bisphosphonate-associated osteonecrosis of the jaw: a case series. Am J Med 123(11):1060–1064

    Article  PubMed  Google Scholar 

  • Ficarra G, Beninati F (2007) Bisphosphonate-related osteonecrosis of the jaws: an update on clinical, pathological and management aspects. Head Neck Pathol 1(2):132–140

    Article  PubMed  Google Scholar 

  • Filleul O, Crompot E, Saussez S (2010) Bisphosphonate-induced osteonecrosis of the jaw: a review of 2,400 patient cases. J Cancer Res Clin Oncol 136(8):1117–1124

    Article  PubMed  Google Scholar 

  • Francis MD, Valent DJ (2007) Historical perspectives on the clinical development of bisphosphonates in the treatment of bone diseases. J Musculoskelet Neuronal Interact 7(1):2–8

    PubMed  Google Scholar 

  • Fugazzotto PA, Lightfoot WS, Jaffin R, Kumar A (2007) Implant placement with or without simultaneous tooth extraction in patients taking oral bisphosphonates: postoperative healing, early follow-up, and the incidence of complications in two private practices. J Periodontol 78(9):1664–1669

    Article  PubMed  Google Scholar 

  • Garcia-Ferrer L, Bagan JV, Martinez-Sanjuan V, Hernandez-Bazan S, Garcia R, Jimenez-Soriano Y et al (2008) MRI of mandibular osteonecrosis secondary to bisphosphonates. AJR Am J Roentgenol 190(4):949–955

    Article  PubMed  Google Scholar 

  • Grant BT, Amenedo C, Freeman K, Kraut RA (2008) Outcomes of placing dental implants in patients taking oral bisphosphonates: a review of 115 cases. J Oral Maxillofac Surg 66(2):223–230

    Article  PubMed  Google Scholar 

  • Harris ST, Watts NB, Genant HK, McKeever CD, Hangartner T, Keller M et al (1999) Effects of risedronate treatment on vertebral and nonvertebral fractures in women with postmenopausal osteoporosis: a randomized controlled trial. Vertebral Efficacy With Risedronate Therapy (VERT) Study Group. JAMA 282(14):1344–1352

    Article  PubMed  Google Scholar 

  • Hokugo A, Christensen R, Chung EM, Sung EC, Felsenfeld AL, Sayre JW et al (2010) Increased prevalence of bisphosphonate-related osteonecrosis of the jaw with vitamin D deficiency in rats. J Bone Miner Res 25(6):1337–1349

    Article  PubMed  Google Scholar 

  • Hutchinson M, O’Ryan F, Chavez V, Lathon PV, Sanchez G, Hatcher DC et al (2010) Radiographic findings in bisphosphonate-treated patients with stage 0 disease in the absence of bone exposure. J Oral Maxillofac Surg 68(9):2232–2240

    Article  PubMed  Google Scholar 

  • Itzstein C, Coxon FP, Rogers MJ (2011) The regulation of osteoclast function and bone resorption by small GTPases. Small GTPases 2(3):117–130

    Article  PubMed  Google Scholar 

  • Jeffcoat MK (2006) Safety of oral bisphosphonates: controlled studies on alveolar bone. Int J Oral Maxillofac Implants 21(3):349–353

    PubMed  Google Scholar 

  • Khosla S, Burr D, Cauley J, Dempster DW, Ebeling PR, Felsenberg D et al (2007) Bisphosphonate-associated osteonecrosis of the jaw: report of a task force of the American Society for Bone and Mineral Research. J Bone Miner Res 22(10):1479–1491

    Article  PubMed  Google Scholar 

  • Kim JH, Park YB, Li Z, Shim JS, Moon HS, Jung HS et al (2011a) Effect of alendronate on healing of extraction sockets and healing around implants. Oral Dis 17(7):705–711

    Article  PubMed  Google Scholar 

  • Kim RH, Lee RS, Williams D, Bae S, Woo J, Lieberman M et al (2011b) Bisphosphonates induce senescence in normal human oral keratinocytes. J Dent Res 90(6):810–816

    Article  PubMed  Google Scholar 

  • Koka S, Babu NM, Norell A (2010) Survival of dental implants in post-menopausal bisphosphonate users. J Prosthodont Res 54(3):108–111

    Article  PubMed  Google Scholar 

  • Kos M, Kuebler JF, Luczak K, Engelke W (2010) Bisphosphonate-related osteonecrosis of the jaws: a review of 34 cases and evaluation of risk. J Craniomaxillofac Surg 38(4):255–259

    Article  PubMed  Google Scholar 

  • Kunchur R, Need A, Hughes T, Goss A (2009) Clinical investigation of C-terminal cross-linking telopeptide test in prevention and management of bisphosphonate-associated osteonecrosis of the jaws. J Oral Maxillofac Surg 67(6):1167–1173

    Article  PubMed  Google Scholar 

  • Kyrgidis A, Vahtsevanos K, Koloutsos G, Andreadis C, Boukovinas I, Teleioudis Z et al (2008) Bisphosphonate-related osteonecrosis of the jaws: a case-control study of risk factors in breast cancer patients. J Clin Oncol 26(28):4634–4638

    Article  PubMed  Google Scholar 

  • Li B, Ling Chau JF, Wang X, Leong WF (2011) Bisphosphonates, specific inhibitors of osteoclast function and a class of drugs for osteoporosis therapy. J Cell Biochem 112(5):1229–1242

    Article  PubMed  Google Scholar 

  • Marx RE (2003) Pamidronate (Aredia) and zoledronate (Zometa) induced avascular necrosis of the jaws: a growing epidemic. J Oral Maxillofac Surg 61(9):1115–1117

    Article  PubMed  Google Scholar 

  • Marx RE, Cillo JE Jr, Ulloa JJ (2007) Oral bisphosphonate-induced osteonecrosis: risk factors, prediction of risk using serum CTX testing, prevention, and treatment. J Oral Maxillofac Surg 65(12):2397–2410

    Article  PubMed  Google Scholar 

  • Marx RE, Sawatari Y, Fortin M, Broumand V (2012) Bisphosphonate-induced exposed bone (­osteonecrosis/osteopetrosis) of the jaws: risk factors, recognition, prevention, and treatment. J Oral Maxillofac Surg 63(11):1567–1575

    Article  Google Scholar 

  • Mawardi H, Giro G, Kajiya M, Ohta K, Almazrooa S, Alshwaimi E et al (2011) A role of oral bacteria in bisphosphonate-induced osteonecrosis of the jaw. J Dent Res 90(1339–45)

    Google Scholar 

  • Meiller T, Almubarak H, Weikel D, Brahim J, Scheper M (2012) Bisphosphonate-associated osteonecrosis of the jaw: are we dealing with a localized non-traditional calciphylaxis? Open Dent J 6:5–7

    Article  PubMed  Google Scholar 

  • Montefusco V, Gay F, Spina F, Miceli R, Maniezzo M, Teresa Ambrosini M et al (2008) Antibiotic prophylaxis before dental procedures may reduce the incidence of osteonecrosis of the jaw in patients with multiple myeloma treated with bisphosphonates. Leuk Lymphoma 49(11):2156–2162

    Article  PubMed  Google Scholar 

  • Morag Y, Morag-Hezroni M, Jamadar DA, Ward BB, Jacobson JA, Zwetchkenbaum SR et al (2009) Bisphosphonate-related osteonecrosis of the jaw: a pictorial review. Radiographics 29(7):1971–1984

    Article  PubMed  Google Scholar 

  • Mozzati M, Martinasso G, Maggiora M, Scoletta M, Zambelli M, Carossa S et al (2012) Oral mucosa produces cytokines and factors influencing osteoclast activity and endothelial cell proliferation, in patients with osteonecrosis of jaw after treatment with zoledronic acid. Clin Oral Investig Aug 3 [Epub ahead of print] DOI: 10.1007/s00784-012-0800-7

  • Narongroeknawin P, Danila MI, Humphreys LGJ, Barasch A, Curtis JR (2010) Bisphosphonate-associated osteonecrosis of the jaw, with healing after teriparatide: a review of the literature and a case report. Spec Care Dentist 30(2):77–82

    Article  PubMed  Google Scholar 

  • Park W, Kim NK, Kim MY, Rhee YM, Kim HJ (2010) Osteonecrosis of the jaw induced by oral administration of bisphosphonates in Asian population: five cases. Osteoporos Int 21(3):527–533

    Article  PubMed  Google Scholar 

  • Reid IR, Cornish J (2011) Epidemiology and pathogenesis of osteonecrosis of the jaw. Nat Rev Rheumatol 29(8):2

    Google Scholar 

  • Roelofs AJ, Stewart CA, Sun S, Blazewska KM, Kashemirov BA, McKenna CE et al (2012) Influence of bone affinity on the skeletal distribution of fluorescently labeled bisphosphonates in vivo. J Bone Miner Res 27(4):835–847

    Article  PubMed  Google Scholar 

  • 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(5):527–534

    Article  PubMed  Google Scholar 

  • Ruggiero SL, Dodson TB, Assael LA, Landesberg R, Marx RE, Mehrotra B (2009) American Association of Oral and Maxillofacial Surgeons position paper on bisphosphonate-related osteonecrosis of the jaws–2009 update. J Oral Maxillofac Surg 67(5 Suppl):2–12

    PubMed  Google Scholar 

  • Shin EY, Kwon YH, Herr Y, Shin SI, Chung JH (2010) Implant failure associated with oral bisphosphonate-related osteonecrosis of the jaw. J Periodontal Implant Sci 40(2):90–95

    Article  PubMed  Google Scholar 

  • Shirota T, Nakamura A, Matsui Y, Hatori M, Nakamura M, Shintani S (2009) Bisphosphonate-related osteonecrosis of the jaw around dental implants in the maxilla: report of a case. Clin Oral Implants Res 20(12):1402–1408

    Article  PubMed  Google Scholar 

  • Solomon DH, Mercer E, Woo SB, Avorn J, Schneeweiss S, Treister N (2012) Defining the epidemiology of bisphosphonate-associated osteonecrosis of the jaw: prior work and current challenges. Osteoporos Int Jun 16. [Epub ahead of print] DOI: 10.1007/s00198-012-2042-6

  • Torres J, Tamimi F, Garcia I, Cebrian JL, Lopez-Cabarcos E, Lopez A (2008) Management of atrophic maxilla in severe osteoporosis treated with bisphosphonates: a case report. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 106(5):668–672

    Article  PubMed  Google Scholar 

  • Vincenzi B, Santini D, Dicuonzo G, Battistoni F, Gavasci M, La Cesa A et al (2005) Zoledronic acid-related angiogenesis modifications and survival in advanced breast cancer patients. J Interferon Cytokine Res 25(3):144–151

    Article  PubMed  Google Scholar 

  • Wang HL, Weber D, McCauley LK (2007) Effect of long-term oral bisphosphonates on implant wound healing: literature review and a case report. J Periodontol 78(3):584–594

    Article  PubMed  Google Scholar 

  • Watts NB, Diab DL (2010) Long-term use of bisphosphonates in osteoporosis. J Clin Endocrinol Metab 95(4):1555–1565

    Article  PubMed  Google Scholar 

  • Weitzman R, Sauter N, Eriksen EF, Tarassoff PG, Lacerna LV, Dias R et al (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(2):148–152

    Article  PubMed  Google Scholar 

  • Yamazaki T, Yamori M, Ishizaki T, Asai K, Goto K, Takahashi K, et al (2012) Increased incidence of osteonecrosis of the jaw after tooth extraction in patients treated with bisphosphonates: a cohort study. Int J Oral Maxillofac Surg 41(11):1397–403

    Google Scholar 

  • Yip JK, Borrell LN, Cho SC, Francisco H, Tarnow DP (2012) Association between oral bisphosphonate use and dental implant failure among middle-aged women. J Clin Periodontol 39(4):408–14

    Article  PubMed  Google Scholar 

  • Yuan K, Chen KC, Chan YJ, Tsai CC, Chen HH, Shih CC (2012) Dental implant failure associated with bacterial infection and long-term bisphosphonate usage: a case report. Implant Dent 21(1):3–7

    Article  PubMed  Google Scholar 

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Authors and Affiliations

  1. The Weintraub Center for Reconstructive Biotechnology, Division of Advanced Prosthodontics, School of Dentistry, University of California Los Angeles, Le Conte Ave 10833, Los Angeles, CA, 90095-1668, USA

    Sil Park

  2. The Weintraub Center for Reconstructive Biotechnology, Divisions of Advanced Prosthodontics and Oral Medicine & Biology, School of Dentistry, University of California Los Angeles, Le Conte Ave 10833, Los Angeles, CA, 90095, USA

    Ichiro Nishimura

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Correspondence to Sil Park .

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  1. School of Dentistry, University of Manchester, Higher Cambridge Street, Manchester, M15 6FH, United Kingdom

    Hugh Devlin

  2. School of Dentistry, University of California Los Angeles, Le Conte Ave 10833, Los Angeles, 90095-1668, California, USA

    Ichiro Nishimura

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Park, S., Nishimura, I. (2013). Bisphosphonates and Dental Implant Treatment. In: Devlin, H., Nishimura, I. (eds) Oral and Cranial Implants. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-34225-7_5

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