Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub. 2020, 164(1):100-107 | DOI: 10.5507/bp.2018.081

Surgical therapy for medication-related osteonecrosis of the jaw in osteoporotic patients treated with antiresorptive agents

Lukas Hauera, Jan Jamburaa, Daniel Hrusaka, Miroslava Chalupovaa, Petr Postaa, Stepan Rusnakb, Vaclav Vyskocilc
a Department of Oral and Maxillofacial Surgery, University Hospital and Faculty of Medicine in Pilsen, Charles University in Prague, Alej Svobody 80, 304 60 Pilsen, Czech Republic
b Clinic of Ophthalmology, University Hospital and Faculty of Medicine in Pilsen, Charles University in Prague, Alej Svobody 80, 304 60 Pilsen, Czech Republic
c Osteocentre of the 2 nd Internal Medicine Clinic, University Hospital and Faculty of Medicine in Pilsen, Charles University in Prague, Dr. Edvarda Benese 13, 305 99 Pilsen, Czech Republic

Background: Medication - related osteonecrosis of the jaw (MRONJ) is a rare but serious complication of antiresorptive and/or antiangiogenic therapy. It mainly affects oncological patients, however, it can occur in patients with metabolic bone diseases, although this is less frequent. These lesions not only significantly impair the quality of life but can also have impact on the treatment of any underlying disease. In some rare cases MRONJ can be life-threatening. There is still no ideal consensus for treatment, though surgical therapy has been mostly preferred in recent years.

Materials and Methods: A monocentric retrospective evaluation of surgical therapy of MRONJ in osteoporotic patients, treated in the time period 3/2014-3/2018 using the uniform department-specific protocol.

Results: 26 osteoporotic patients with 32 MRONJ lesions of stage 1 (9%), stage 2 (75%) and stage 3 (16%) were treated surgically. The maxilla: mandibula ratio was 1:2.2, in 19% of patients there was multiple jaw involvement. 69.2% of patients had received bisphosphonates, 15.4% denosumab and 15.4% had a history of both types of antiresorptive treatment. Complete healing was observed in all patients, in 9% of cases by secondary intention in the mean period of 6 weeks. The mean follow-up was 20.5 months.

Conclusion: The presented protocol for surgical therapy was effective in the management of all MRONJ stages in the osteoporotic patients described here. The surgery is indicated as an early treatment to prevent complications and the progression of the lesions. It leads to improvement in quality of life and option to resume antiresorptive therapy if interrupted.

Keywords: osteonecrosis of the jaw, MRONJ, antiresorptive drugs, osteoporosis, fluorescence-guided surgery

Received: September 25, 2018; Accepted: December 18, 2018; Prepublished online: January 10, 2019; Published: March 26, 2020  Show citation

ACS AIP APA ASA Harvard Chicago Chicago Notes IEEE ISO690 MLA NLM Turabian Vancouver
Hauer, L., Jambura, J., Hrusak, D., Chalupova, M., Posta, P., Rusnak, S., & Vyskocil, V. (2020). Surgical therapy for medication-related osteonecrosis of the jaw in osteoporotic patients treated with antiresorptive agents. Biomedical papers, 164(1), 100-107. doi: 10.5507/bp.2018.081
Share...
Download citation
  • BibTeX (.bib)
  • Bookends (.ris)
  • EasyBib (.ris)
  • EndNote (.enw)
  • EndNote 8 (.xml)
  • ISI WoS (.isi)
  • Medlars (.medlars)
  • Mendeley (.ris)
  • MODS (.xml)
  • Papers (.ris)
  • RefWorks (.txt)
  • RefManager (.ris)
  • RIS (.ris)
  • MS Word (.xml)
  • Zotero (.ris)
    • Open full article

    References

    1. Cooper C, Campion G, Melton LJ. Hip fractures in the elderly: a world-wide projection. Osteoporos Int 1992;2(6):285-9. Go to original source... Go to PubMed...
    2. Sotornik I. Osteoporóza - epidemiologie a patogeneze. Vnitř Lék 2016; 62(12, Suppl 6):6S84-7.
    3. Aljohani S, Fliefel R, Ihbe J, Kühnisch J, Ehrenfeld M, Otto S. What is the effect of anti-resorptive drugs (ARDs) on the development of medication-related osteonecrosis of the jaw (MRONJ) in osteoporosis patients: A systematic review. J Craniomaxillofac Surg 2017;45(9):1493-502. Go to original source... Go to PubMed...
    4. Ruggiero SL, Dodson TB, Fantasia J, Goodday R, Aghaloo T, Mehrotra B, O'Ryan F. American Association of Oral and Maxillofacial Surgeons position Paper on Medication-Related Osteonecrosis of the Jaws- 2014 Update. J Oral Maxillofac Surg 2014;72(10):1938-56. Go to original source... Go to PubMed...
    5. Otto S, Pautke C, Van den Wyngaert T, Niepel D, Schiødt M. Medication-related osteonecrosis of the jaw: Prevention, diagnosis and management in patients with cancer and bone metastases. Cancer Treat Rev 2018 Jun 18.[Epub ahead of print] doi: 10.1016/j.ctrv.2018.06.007 Go to original source... Go to PubMed...
    6. Bodem JP, Kargus S, Engel M, Hoffmann J, Freudlsperger C. Value of nonsurgical therapeutic management of stage I bisphosphonate-related osteonecrosis of the jaw. J Craniomaxillofac Surg 2015;43(7):1139-43. Go to original source... Go to PubMed...
    7. Ristow O, Otto S, Troeltzsch M, Hohlweg-Majert B, Pautke C. Treatment perspectives for medication-related osteonecrosis of the jaw (MRONJ). J Craniomaxillofac Surg 2015;43(2):290-3. Go to original source... Go to PubMed...
    8. Khan AA, Morrison A, Kendler DL, Rizzoli R, Hanley DA, Felsenberg D, McCauley LK, O'Ryan F, Reid IR, Ruggiero SL, Taguchi A, Tetradis S, Watts NB, Brandi ML, Peters E, Guise T, Eastell R, Cheung AM, Morin SN, Masri B, Cooper C, Morgan SL, Obermayer-Pietsch B, Langdahl BL, Dabagh RA, Davison KS, Sándor GK, Josse RG, Bhandari M, El Rabbany M, Pierroz DD, Sulimani R, Saunders DP, Brown JP, Compston J; International Task Force on Osteonecrosis of the Jaw. Case-Based Review of Osteonecrosis of the Jaw (ONJ) and Application of the International Recommendations for Management From the International Task Force on ONJ. J Clin Densitom 2017;20(1):8-24. Go to original source... Go to PubMed...
    9. Troeltzsch M, Woodlock T, Kriegelstein S, Steiner T, Messlinger K, Troeltzsch M. Physiology and pharmacology of nonbisphosphonate drugs implicated in osteonecrosis of the jaw. J Can Dent Assoc 2012;78:c85. Go to PubMed...
    10. Fung P, Bedogni G, Bedogni A, Petrie A, Porter S, Campisi G, Bagan J, Fusco V, Saia G, Acham S, Musto P, Petrucci MT, Diz P, Colella G, Mignogna MD, Pentenero M, Arduino P, Lodi G, Maiorana C, Manfredi M, Hallberg P, Wadelius M, Takaoka K, Leung YY, Bonacina R, Schiødt M, Lakatos P, Taylor T, De Riu G, Favini G, Rogers SN, Pirmohamed M, Nicoletti P; GENVABO Consortium, Fedele S. Time to onset of bisphosphonate-related osteonecrosis of the jaws: a multicentre retrospective cohort study. Oral Dis 2017;23(4):477-83. Go to original source... Go to PubMed...
    11. Lo JC, O'Ryan FS, Gordon NP, Yang J, Hui RL, Martin D, Hutchinson M, Lathon PV, Sanchez G, Silver P, Chandra M, McCloskey CA, Staffa JA, Willy M, Selby JV, Go AS; Predicting Risk of Osteonecrosis of the Jaw with Oral Bisphosphonate Exposure (PROBE) Investigators. Prevalence of osteonecrosis of the jaw in patients with oral bisphosphonate exposure. J Oral Maxillofac Surg 2010;68(2):243-53. Go to original source... Go to PubMed...
    12. Grbic JT, Black DM, Lyles KW, Reid DM, Orwoll E, McClung M, Bucci-Rechtweg C, Su G. The incidence of osteonecrosis of the jaw in patients receiving 5 milligrams of zoledronic acid: data from the health outcomes and reduced incidence withzoledronic acid once yearly clinicaltrials program. J Am Dent Assoc 2010;141(11):1365-70. Go to original source... Go to PubMed...
    13. Compston J. Safety of long-term denosumab therapy for osteoporosis. Lancet Diabetes Endocrinol 2017;5(7):485-7. Go to original source... Go to PubMed...
    14. Otto S, Pautke C, Opelz C, Westphal I, Drosse I, Schwager J, Bauss F, Ehrenfeld M, Schieker M. Osteonecrosis of the jaw: effect of bisphosphonate type, local concentration, and acidic milieu on the pathomechanism. J Oral Maxillofac Surg 2010;68(11):2837-45. Go to original source... Go to PubMed...
    15. McGowan K, McGowan T, Ivanovski S. Risk factors for medication-related osteonecrosis of the jaws: A systematic review. Oral Dis 2018;24(4):527-36. Go to original source... Go to PubMed...
    16. Beth-Tasdogan NH, Mayer B, Hussein H, Zolk O. Interventions for managing medication-related osteonecrosis of the jaw. Cochrane Database Syst Rev 2017;10:CD012432. Go to original source... Go to PubMed...
    17. 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. Frequency and risk factors associated with osteonecrosis of the jaw in cancer patients treated with intravenous bisphosphonates. J Bone Miner Res 2008;23(6):826-36. Go to original source... Go to PubMed...
    18. Lazarovici TS, Yahalom R, Taicher S, Elad S, Hardan I, Yarom N. Bisphosphonate related osteonecrosis of the jaws: a single- center study of 101 patients. J Oral Maxillofac Surg 2009;67(4):850-5. Go to original source... Go to PubMed...
    19. Graziani F, Vescovi P, Campisi G, Favia G, Gabriele M, Gaeta GM, Gennai S, Goia F, Miccoli M, Peluso F, Scoletta M, Solazzo L, Colella G. Resective surgical approach shows a high performance in the management of advanced cases of bisphosphonate-related osteonecrosis of the jaws: a retrospective survey of 347 cases. J Oral Maxillofac Surg 2012;70(11):2501-7. Go to original source... Go to PubMed...
    20. Holzinger D, Seemann R, Klug C, Ewers R, Millesi G, Baumann A, Wutzl A. Long-term success of surgery in bisphosphonate-related osteonecrosis of the jaws (BRONJs). Oral Oncol 2013;49(1):66-70. Go to original source... Go to PubMed...
    21. Stockmann P, Vairaktaris E, Wehrhan F, Seiss M, Schwarz S, Spriewald B, Neukam FW, Nkenke E. Osteotomy and primary wound closure in bisphosphonate-associated osteonecrosis of the jaw: a prospective clinical study with 12 months follow-up. Support Care Cancer 2010;18(4):449-60. Go to original source... Go to PubMed...
    22. Stockmann P, Burger M, von Wilmowsky C, Ebker T, Lutz R, Bauersachs A, Nkenke E, Neukam FW, Wehrhan F. The outcome after surgical therapy of bisphosphonate-associated osteonecrosis of the jaw-results of a clinical case series with an average follow-up of 20 months. Clin Oral Investig 2014;18(4):1299-304. Go to original source... Go to PubMed...
    23. Carlson ER, Basile JD. The role of surgical resection in the management of bisphosphonate-related osteonecrosis of the jaws. J Oral Maxillofac Surg 2009;67(5 Suppl):85-95. Go to original source... Go to PubMed...
    24. Assaf AT, Zrnc TA, Riecke B, Wikner J, Zustin J, Friedrich RE, Heiland M, Smeets R, Gröbe A. Intraoperative efficiency of fluorescence imaging by Visually Enhanced Lesion Scope (VELscope®) in patients with bisphosphonate related osteonecrosis of the jaw (BRONJ). J Craniomaxillofac Surg 2014;42(5):e157-64. Go to original source... Go to PubMed...
    25. Voss PJ, Joshi Oshero J, Kovalova-Müller A, Veigel Merino EA, Sauerbier S, Al-Jamali J, Lemound J, Metzger MC, Schmelzeisen R. Surgical treatment of bisphosphonate-associated osteonecrosis of the jaw: technical report and follow up of 21 patients. J Craniomaxillofac Surg 2012;40(8):719-25. Go to original source... Go to PubMed...
    26. Williamson RA. Surgical management of bisphosphonate induced osteonecrosis of the jaws. Int J Oral Maxillofac Surg 2010;39(3):251-5. Go to original source... Go to PubMed...
    27. Otto S, Ristow O, Pache C, Troeltzsch M, Fliefel R, Ehrenfeld M, Pautke C. Fluorescence-guided surgery for the treatment of medication-related osteonecrosis of the jaw: A prospective cohort study. J Craniomaxillofac Surg 2016;44(8):1073-80. Go to original source... Go to PubMed...
    28. Otto S, Baumann S, Ehrenfeld M, Pautke C. Successful surgical management of osteonecrosis of the jaw due to RANK-ligand inhibitor treatment using fluorescence guided bone resection. J Craniomaxillofac Surg 2013;41(7):694-8. Go to original source... Go to PubMed...
    29. Hoefert S, Yuan A, Munz A, Grimm M, Elayouti A, Reinert S. Clinical course and therapeutic outcomes of operatively and non-operatively managed patients with denosumab-related osteonecrosis of the jaw (DRONJ). J Craniomaxillofac Surg 2017;45(4):570-8. Go to original source... Go to PubMed...
    30. Pichardo SE, van Merkesteyn JP. Evaluation of a surgical treatment of denosumab-related osteonecrosis of the jaws. Oral Surg Oral Med Oral Pathol Oral Radiol 2016;122(3):272-8. Go to original source... Go to PubMed...
    31. Lesclous P, Grabar S, Abi Najm S, Carrel JP, Lombardi T, Saffar JL, Samson J. Relevance of surgical management of patients affected by bisphosphonate-associated osteonecrosis of the jaws. A prospective clinical and radiological study. Clin Oral Investig 2014;18(2):391-9. Go to original source... Go to PubMed...
    32. Hayashida S, Soutome S, Yanamoto S, Fujita S, Hasegawa T, Komori T, Kojima Y, Miyamoto H, Shibuya Y, Ueda N, Kirita T, Nakahara H, Shinohara M, Umeda M. Evaluation of the Treatment Strategies for Medication-Related Osteonecrosis of the Jaws (MRONJ) and the Factors Affecting Treatment Outcome: A Multicenter Retrospective Study with Propensity Score Matching Analysis. J Bone Miner Res 2017;32(10):2022-9. Go to original source... Go to PubMed...
    33. Bagan J, Peydró A, Calvo J, Leopoldo M, Jiménez Y, Bagan L. Medication-related osteonecrosis of the jaw associated with bisphosphonates and denosumab in osteoporosis. Oral Dis 2016;22(4):324-9. Go to original source... Go to PubMed...
    34. Nisi M, Karapetsa D, Gennai S, Ramaglia L, Graziani F, Gabriele M. Conservative surgical treatment of medication related osteonecrosis of the jaw (MRONJ) lesions in patients affected by osteoporosis exposed to oral bisphosphonates: 24 months follow-up. J Craniomaxillofac Surg 2018;46(7):1153-8. Go to original source... Go to PubMed...
    35. Kaehling Ch, Streckbein P, Schmermund D, Henrich M, Burchert D, Gattenloehner S, Howaldt HP, Wilbrand JF. Lethal cervical abscess following bisphosphonate related osteonecrosis of the jaw. J Craniomaxillofac Surg 2014;42(7):1203-6. Go to original source... Go to PubMed...
    36. Ristow O, Otto S, Geiß C, Kehl V, Berger M, Troeltzsch M, Koerdt S, Hohlweg-Majert B, Freudlsperger C, Pautke C. Comparison of auto-fluorescence and tetracycline fluorescence for guided bone surgery of medication-related osteonecrosis of the jaw: a randomized controlled feasibility study. Int J Oral Maxillofac Surg 2017;46(2):157-66. Go to original source... Go to PubMed...
    37. Melville JC, Tursun R, Shum JW, Young S, Hanna IA, Marx RE. A technique for the treatment of oral-antral fistulas resulting from medication-related osteonecrosis of the maxilla: the combined buccal fat pad flap and radical sinusotomy. Oral Surg Oral Med Oral Pathol Oral Radiol 2016;122(3):287-91. Go to original source... Go to PubMed...
    38. Gallego L, Junquera L, Pelaz A, Hernando J, Megías J.The use of pedicled buccal fat pad combined with sequestrectomy in bisphosphonate-related osteonecrosis of the maxilla. Med Oral Patol Oral Cir Bucal 2012;17(2):e236-41. Go to original source... Go to PubMed...
    39. Berrone M, Florindi FU, Carbone V, Aldiano C, Pentenero M. Stage 3 Medication-Related Osteonecrosis of the Posterior Maxilla: Surgical Treatment Using a Pedicled Buccal Fat Pad Flap: Case Reports. J Oral Maxillofac Surg 2015;73(11):2082-6. Go to original source... Go to PubMed...
    40. Rotaru H, Kim MK, Kim SG, Park YW. Pedicled buccal fat pad flap as a reliable surgical strategy for the treatment of medication-related osteonecrosis of the jaw. J Oral Maxillofac Surg 2015;73(3):437-42. Go to original source... Go to PubMed...
    41. Mücke T, Koerdt S, Jung M, Mitchell DA, Wolff KD, Kesting MR, Loeffelbein DJ. The role of mylohyoid flap in the treatment of bisphosphonate-related osteonecrosis of the jaws. J Craniomaxillofac Surg 2016;44(4):369-73. Go to original source... Go to PubMed...
    42. Epstein MS, Ephros HD, Epstein JB. Review of current literature and implications of RANKL inhibitors for oral health care providers. Oral Surg Oral Med Oral Pathol Oral Radiol 2013;116(6):e437-42. Go to original source... Go to PubMed...

    This is an open access article distributed under the terms of the Creative Commons Attribution 4.0 International License (CC BY 4.0), which permits use, distribution, and reproduction in any medium, provided the original publication is properly cited. No use, distribution or reproduction is permitted which does not comply with these terms.


    Return to the content