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01-03-2015 | Original Article

Tooth alterations in areas of bisphosphonate-induced osteonecrosis

Authors: Paulo de Camargo Moraes, Carolina Amália Barcellos Silva, Andresa Borges Soares, Fabrício Passador-Santos, Maria Elvira Pizzigatti Corrêa, Ney Soares de Araújo, Vera Cavalcanti de Araújo

Published in: Clinical Oral Investigations | Issue 2/2015

Abstract

Objective

Osteonecrosis of the jaw is a potential side effect when using bisphosphonates. Most studies on the effects of bisphosphonates on teeth have been conducted in vitro or in animal models of tooth development. Therefore, the aim of this study was to describe alterations found in human teeth extracted from areas of bisphosphonate-induced osteonecrosis.

Materials and methods

Using a retrospective study design, 16 teeth from 13 patients were extracted from areas of bisphosphonate-induced osteonecrosis during surgical debridement. The specimens were decalcified and embedded in paraffin. A series of 5-μm sections were prepared, stained with hematoxylin and eosin (H&E) and observed under a light microscope.

Results

The majority of the patients were female (53.85 %), with a mean age of 60.23 ± 13.18 years. Zoledronate (IV) was the most common bisphosphonate used (92.3 %), over a mean period of 2 years. The commonest alteration observed was hypercementosis (87.5 %), followed by pulpar necrosis (81.25 %), pulp stones attached to the dentine and loose pulp stones in the pulp chamber and root canals in addition to linear calcifications (68.75 %), dentinoid/osteoid material formation (18.75 %), and dental ankylosis (6.25 %).

Conclusions

Patients undergoing bisphosphonate therapy present diverse tooth alterations, which should be closely monitored by clinicians to prevent complications.

Clinical relevance

It is paramount that the teeth involved in oral lesions are always examined. Attention should be drawn to the need to establish preventive measures, in terms of dental treatment, for patients prior to starting bisphosphonate therapy.

Pozzi S, Raje N (2011) The role of bisphosphonates in multiple myeloma: mechanisms, side effects, and the future. Oncologist 16:651–662. doi:10.1634/theoncologist.2010-0225 CrossRefPubMedCentralPubMed

Santamaria Junior M, Fracalossi ACC, Consolaro MFMO, Consolaro A (2010) Influence of bisphosphonates on alveolar bone density: a histomorphometric analysis. Braz Oral Res 24:309–315

Dominguez LJ, Di Bella G, Belvedere M, Barbagallo M (2011) Physiology of the aging bone and mechanisms of action of bisphosphonates. Biogerontology 12:397–408. doi:10.1007/s10522-011-9344-5 CrossRefPubMed

Drake MT, Clarke BL, Khosla S (2008) Bisphosphonates: Mechanism of action and role in clinical practice. Mayo Clin Proc 83:1032–1045. doi:10.4065/83.9.1032 CrossRefPubMedCentralPubMed

Antonini F, Pereira CCS, Parente EV, Azambuja FG (2010) Management of osteonecrosis of the jaws in patients with history of bisphosphonates therapy. J Craniofac Surg 21:1962–1966. doi:10.1097/SCS.0b013e3181f4ee4e CrossRefPubMed

Kuhl S, Walter C, Acham S, Pfeffer R, Lambrecht JT (2012) Bisphosphonate-related osteonecrosis of the jaws—a review. Oral Oncol 48:938–947. doi:10.1016/j.oraloncology.2012.03.028 CrossRefPubMed

Grbic JT, Landesberg R, Lin SQ, Mesenbrink P, Reid IR, Leung PC, Casas N et al (2008) Incidence of osteonecrosis of the jaw in women with postmenopausal osteoporosis in the Health Outcomes and Reduced Incidence With Zoledronic Acid Once Yearly Pivotal Fracture Trial. J Am Dent Assoc 139:32–40CrossRefPubMed

Boonyapakorn T, Schirmer I, Reichart PA, Sturm I, Massenkeil G (2008) Bisphosphonate-induced osteonecrosis of the jaws: prospective study of 80 patients with multiple myeloma and other malignancies. Oral Oncol 44:857–869. doi:10.1016/j.oraloncology.2007.11.012 CrossRefPubMed

Mavrokokki T, Cheng A, Stein B, Goss A (2007) Nature and frequency of bisphosphonate-associated osteonecrosis of the jaws in Australia. J Oral Maxillofac Surg 65:415–423CrossRefPubMed

10.

Assael LA (2011) Bisphosphonates and Oral health: primer and an update for the practing surgeon. Oral Maxillofac Surg Clin North Am 23:443–453. doi:10.1016/j.coms.2011.04.002 CrossRefPubMed

11.

Ravosa MJ, Ning J, Liu Y, Stack MS (2011) Bisphosphonate effects on the behavior of oral epithelial cells and oral fibroblasts. Arch Oral Biol 56:491–498. doi:10.1016/j.archoralbio.2010.11.003 CrossRefPubMed

12.

Kim J, Park YB, Li Z, Shim JS, Moon HS, Jung HS, Chung MK (2011) Effect of alendronate on healing of extraction sockets and healing around implants. Oral Dis 17:705–711. doi:10.1111/j.1601-0825.2011.01829.x CrossRefPubMed

13.

Ruggiero SL, Fantasia J, Carlson E (2006) Bisphosphonate-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

14.

Roelofs AJ, Thompson K, Gordon S, Rogers M (2006) Molecular mechanisms of action of bisphosphonates: current status. Clin Cancer Res 12:6222–6230sCrossRef

15.

Fleisch H (1998) Bisphosphonates: mechanisms of action. Endocr Rev 19:80–100CrossRefPubMed

16.

Ruggiero SL, Dodson TB, Assael LA, Landesberg R, Marx RE, Mehrotra B (2009) American Association of Oral and Maxillofacial Surgeons position paper: Bisphosphonate-Related Osteonecrosis of the Jaws-2009 update. J Oral Maxillofac Surg 67(5 Suppl):2–12. doi:10.1016/j.joms.2009.01.009 PubMed

17.

Vermeer JAF, Jansen ID, Marthi M, Coxon FP, McKenna CE, Sun S, de Vries TJ, Everts V (2013) Jaw bone marrow-derived osteoclast precursors internalize more bisphosphonate than long-bone marrow precursors. Bone 57:242–251. doi:10.1016/j.bone.2013.08.007 CrossRefPubMed

18.

Silverman SL, Landesberg R (2009) Osteonecrosis of the jaw and the role of bisphosphonates: a critical review. Am J Med 122(2 Suppl):33–45. doi:10.1016/j.amjmed.2008.12.005 CrossRef

19.

Urade M, Tanaka N, Furusawa K, Shimada J, Shibata T, Kirita T, Yamamoto T et al (2011) Nationwide survey for bisphosphonate-related osteonecrosis of the jaws in Japan. J Oral Maxillofac Surg 69:e364–e371. doi:10.1016/j.joms.2011.03.051 CrossRefPubMed

20.

Borromeo GL, Tsao CE, Darby IB, Ebeling PR (2011) A review of the clinical implications of bisphosphonates in dentistry. Aust Dent J 56:2–9. doi:10.1111/j.1834-7819.2010.01283.x CrossRefPubMed

21.

McLeod NMH, Patel V, Kusanale A, Rogers SN, Brennan PA (2011) Bisphosphonate osteonecrosis of the jaw: a literature review of UK policies versus international policies on the management of bisphosphonate osteonecrosis of the jaw. Br J Oral Maxillofac Surg 49:335–342. doi:10.1016/j.bjoms.2010.08.005 CrossRefPubMed

22.

Allen MR, Burr DB (2009) The pathogenesis of bisphosphonate-related osteonecrosis of the jaw: so many hypotheses, so few data. J Oral Maxillofac Surg 67(5 Suppl):61–70. doi:10.1016/j.joms.2009.01.007 CrossRefPubMed

23.

Wehrhan F, Stockmann P, Nkenke E, Schlegel KA, Guentsch A, Wehrhan T, Neukam FW, Amann K (2011) Differential impairment of vascularization and angiogenesis in bisphosphonate-associated osteonecrosis of the jaw-related mucoperiosteal tissue. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 112:216–221. doi:10.1016/j.tripleo.2011.02.028 CrossRefPubMed

24.

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 139:1674–1677CrossRefPubMed

25.

Morse DR (1991) Age-related changes of the dental pulp complex and their relationship to systemic aging. Oral Surg Oral Med Oral Pathol 72:721–745CrossRefPubMed

26.

Wesselink PR, Beertsen W (1989) The influence of 1-hydroxyethylidene-1,1-bisphosphonate (HEBP) on dental root resorption in the mouse. Calcif Tissue Int 45:104–110CrossRefPubMed

27.

Alatli-Kut I, Hultenby K, Hammarstrom L (1994) Disturbances of cementum formation induced by single injection of 1-hydroxyethylidene-1,1-bisphosphonate (HEPB) in rats: light and scanning electron microscopic studies. Scand J Dent Res 102:260–268PubMed

28.

Brandsten C, Alatli I, Wurtz T, Hammarstrom L (1995) Coronal dentinal nodules induced by single or multiple injections of HEPB in young rats. Connect Tissue Res 32:275–279CrossRefPubMed

29.

Sener S, Cobankara FK, Akgünlü F (2009) Calcifications of the pulp chamber: prevalence and implicated factors. Clin Oral Investg 13:209–215. doi:10.1007/s00784-008-0212-x CrossRef

30.

Coxon FP, Thompson K, Roelofs AJ, Hal Ebetino F, Rogers MJ (2008) Visualizing mineral binding and uptake of bisphosphonate by osteoclasts and non-resorbing cells. Bone 42:848–860. doi:10.1016/j.bone.2007.12.225 CrossRefPubMed

31.

Pichardo SE, Merkesteyn JP (2013) Bisphosphonate related osteonecrosis of the jaws: spontaneous or dental origin? Oral Surg Oral Med Oral Pathol Oral Radiol 116:287–292. doi:10.1016/j.oooo.2013.05.005 CrossRefPubMed

32.

Cvikl B, Agis H, Stogerer K, Moritz A, Watzek G, Gruber R (2011) The response of dental pulp-derived cells to zoledronate depends on the experimental model. Int Endod J 44:33–40. doi:10.1111/j.1365-2591.2010.01792.x CrossRefPubMed

Title: Tooth alterations in areas of bisphosphonate-induced osteonecrosis
Authors: Paulo de Camargo Moraes
Carolina Amália Barcellos Silva
Andresa Borges Soares
Fabrício Passador-Santos
Maria Elvira Pizzigatti Corrêa
Ney Soares de Araújo
Vera Cavalcanti de Araújo
Publication date: 01-03-2015
Publisher: Springer Berlin Heidelberg
Published in: Clinical Oral Investigations / Issue 2/2015
Print ISSN: 1432-6981
Electronic ISSN: 1436-3771
DOI: https://doi.org/10.1007/s00784-014-1270-x

At a glance: The STEP trials

Springer Medicine

Tooth alterations in areas of bisphosphonate-induced osteonecrosis

Abstract

Objective

Materials and methods

Results

Conclusions

Clinical relevance

At a glance: The STEP trials

Springer Medicine

Abstract

Objective

Materials and methods

Results

Conclusions

Clinical relevance

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