Journal of the Korean Association of Oral and Maxillofacial Surgeons

The Korean Association of Oral and Maxillofacial Surgeons (대한구강악안면외과학회)
권호 표지
DOI QR코드

DOI QR Code

Clinical investigation of bisphosphonate-related osteonecrosis of the jaws in patients with malignant tumors

  • Kim, Sei-Kyoung (Department of Oral and Maxillofacial Surgery, School of Dentistry, Kyungpook National University) ;
  • Kwon, Tae-Geon (Department of Oral and Maxillofacial Surgery, School of Dentistry, Kyungpook National University)
  • Received : 2012.03.29
  • Accepted : 2012.05.08
  • Published : 2012.06.30
Download PDF
⟨ Previous Next ⟩

Abstract

Objectives: This study evaluated bisphosphonate-related osteonecrosis of the jaws (BRONJ) in patients diagnosed with malignant bone tumors. Demographic findings, laboratory, and radiographic analyses were performed to characterize disease severity and progression. Materials and Methods: Patients who had been diagnosed with BRONJ (2005-2010) at the authors' hospital according to the American Association of Oral and Maxillofacial Surgeons were investigated. Twenty-one patients (12 with multiple myelomas, 7 with breast cancer, and 2 with prostate cancer) who had been treated with bisphosphonates (BPs) for malignant bone tumors were included. Radiographic evaluations with a panorama, computed tomography, whole body bone scan, and laboratory findings were evaluated for erythrocyte sedimentation rate (ESR), c-reactive proteins (CRPs), and c-terminal cross-linked telopeptides (CTXs). Results: The average age of the patients was 64.3 (range 51-80), and they were treated with BPs for an average of $35{\pm}19$ months before BRONJ was diagnosed. Types of BPs were zolendronic acid (81%, intravenous [IV]), pamidronate (4.8%, IV), zoledronic acid+pamidronate (4.8%, IV), alendronate (4.8%, per os [PO]), and ibadronate (4.75%, PO). Extraction (67%) and persistent irritation of dentures (20%) were the most common triggering factors. BRONJ in the mandible was reported in 62% of the cases, in the maxilla 24%, and both 14%. BRONJ occurred more frequently in patients with multiple myelomas (n=12, 57.1%). Most of the patients revealed an advanced BRONJ stage; Stage I (n=2, 9%), Stage II (n=13, 62%), and Stage III (n=6, 29%). Conclusion: The differences of the ESR, CRP, and CTX values between the BRONJ-recurring and non-recurring patients after the treatment were not evident. Later stage BRONJ patients showed lower CTX levels. A drug holiday after the diagnosis of BRONJ did not remarkably influence the surgical outcomes. However, the limited number of patients in the study should be considered.

Keywords

References

  1. Marx RE, Sawatari Y, Fortin M, Broumand V. Bisphosphonate-induced exposed bone (osteonecrosis/osteopetrosis) of the jaws: risk factors, recognition, prevention, and treatment. J Oral Maxillofac Surg 2005;63:1567-75.
  2. Madrid C, Bouferrache K, Abarca M, Jaques B, Broome M. Bisphosphonate-related osteonecrosis of the jaws: how to manage cancer patients. Oral Oncol 2010;46:468-70.
  3. Gutta R, Louis PJ. Bisphosphonates and osteonecrosis of the jaws: science and rationale. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2007;104:186-93.
  4. Woo SB, Hellstein JW, Kalmar JR. Systematic review: bisphosphonates and osteonecrosis of the jaws. Ann Intern Med 2006;144: 753-61.
  5. Coleman R. The use of bisphosphonates in cancer treatment. Ann N Y Acad Sci 2011;1218:3-14.
  6. Matsumoto S, Kimura S, Segawa H, Kuroda J, Yuasa T, Sato K, et al. Efficacy of the third-generation bisphosphonate, zoledronic acid alone and combined with anti-cancer agents against small cell lung cancer cell lines. Lung Cancer 2005;47:31-9.
  7. Owens G, Jackson R, Lewiecki EM. An integrated approach: bisphosphonate management for the treatment of osteoporosis. Am J Manag Care 2007;13 Suppl 11:S290-308.
  8. Marx RE. Pamidronate (Aredia) and zoledronate (Zometa) induced avascular necrosis of the jaws: a growing epidemic. J Oral Maxillofac Surg 2003;61:1115-7.
  9. Ruggiero SL, Dodson TB, Assael LA, Landesberg R, Marx RE, Mehrotra B; Task Force on Bisphosphonate-Related Osteonecrosis of the Jaws, American Association of Oral and Maxillofacial Surgeons. American Association of Oral and Maxillofacial Surgeons position paper on bisphosphonate-related osteonecrosis of the jaw - 2009 update. Aust Endod J 2009;35:119-30.
  10. Lam DK, Sandor GK, Holmes HI, Evans AW, Clokie CM. A review of bisphosphonate-associated osteonecrosis of the jaws and its management. J Can Dent Assoc 2007;73:417-22.
  11. Hoff AO, Toth BB, Altundag K, Johnson MM, Warneke CL, Hu M, et al. Frequency and risk factors associated with osteonecrosis of the jaw in cancer patients treated with intravenous bisphosphonates. J Bone Miner Res 2008;23:826-36.
  12. Ortega C, Montemurro F, Faggiuolo R, Vormola R, Nanni D, Goia F, et al. Osteonecrosis of the jaw in prostate cancer patients with bone metastases treated with zoledronate: a retrospective analysis. Acta Oncol 2007;46:664-8.
  13. Bamias A, Kastritis E, Bamia C, Moulopoulos LA, Melakopoulos I, Bozas G, et al. Osteonecrosis of the jaw in cancer after treatment with bisphosphonates: incidence and risk factors. J Clin Oncol 2005;23:8580-7.
  14. Wang EP, Kaban LB, Strewler GJ, Raje N, Troulis MJ. Incidence of osteonecrosis of the jaw in patients with multiple myeloma and breast or prostate cancer on intravenous bisphosphonate therapy. J Oral Maxillofac Surg 2007;65:1328-31.
  15. Vahtsevanos K, Kyrgidis A, Verrou E, Katodritou E, Triaridis S, Andreadis CG, et al. Longitudinal cohort study of risk factors in cancer patients of bisphosphonate-related osteonecrosis of the jaw. J Clin Oncol 2009;27:5356-62.
  16. Ruggiero S, Gralow J, Marx RE, Hoff AO, Schubert MM, Huryn JM, et al. Practical guidelines for the prevention, diagnosis, and treatment of osteonecrosis of the jaw in patients with cancer. J Oncol Pract 2006;2:7-14.
  17. Mehrotra B. Bisphosphonates--role in cancer therapies. J Oral Maxillofac Surg 2009;67(5 Suppl):19-26.
  18. Daley-Yates PT, Dodwell DJ, Pongchaidecha M, Coleman RE, Howell A. The clearance and bioavailability of pamidronate in patients with breast cancer and bone metastases. Calcif Tissue Int 1991;49:433-5.
  19. Coleman RE. Bisphosphonates: clinical experience. Oncologist 2004;9 Suppl 4:14-27.
  20. Rosen LS, Gordon D, Kaminski M, Howell A, Belch A, Mackey J, et al. Long-term efficacy and safety of zoledronic acid compared with pamidronate disodium in the treatment of skeletal complications in patients with advanced multiple myeloma or breast carcinoma: a randomized, double-blind, multicenter, comparative trial. Cancer 2003;98:1735-44.
  21. Saad F, Gleason DM, Murray R, Tchekmedyian S, Venner P, Lacombe L, et al; Zoledronic Acid Prostate Cancer Study Group. Long-term efficacy of zoledronic acid for the prevention of skeletal complications in patients with metastatic hormone-refractory prostate cancer. J Natl Cancer Inst 2004;96:879-82.
  22. Rosen LS, Gordon D, Tchekmedyian S, Yanagihara R, Hirsh V, Krzakowski M, et al. Zoledronic acid versus placebo in the treatment of skeletal metastases in patients with lung cancer and other solid tumors: a phase III, double-blind, randomized trial--the Zoledronic Acid Lung Cancer and Other Solid Tumors Study Group. J Clin Oncol 2003;21:3150-7.
  23. Corey E, Brown LG, Quinn JE, Poot M, Roudier MP, Higano CS, et al. Zoledronic acid exhibits inhibitory effects on osteoblastic and osteolytic metastases of prostate cancer. Clin Cancer Res 2003;9:295-306.
  24. Wood J, Bonjean K, Ruetz S, Bellahcene A, Devy L, Foidart JM, et al. Novel antiangiogenic effects of the bisphosphonate compound zoledronic acid. J Pharmacol Exp Ther 2002;302:1055-61.
  25. Madrid C, Sanz M. What impact do systemically administrated bisphosphonates have on oral implant therapy? A systematic review. Clin Oral Implants Res 2009;20 Suppl 4:87-95.
  26. McClung MR. Bisphosphonates. Endocrinol Metab Clin North Am 2003;32:253-71.
  27. Phal PM, Myall RW, Assael LA, Weissman JL. Imaging findings of bisphosphonate-associated osteonecrosis of the jaws. AJNR Am J Neuroradiol 2007;28:1139-45.
  28. Eckert AW, Maurer P, Meyer L, Kriwalsky MS, Rohrberg R, Schneider D, et al. Bisphosphonate-related jaw necrosis--severe complication in maxillofacial surgery. Cancer Treat Rev 2007;33: 58-63.
  29. Price PA, Parthemore JG, Deftos LJ. New biochemical marker for bone metabolism. Measurement by radioimmunoassay of bone GLA protein in the plasma of normal subjects and patients with bone disease. J Clin Invest 1980;66:878-83.
  30. Duda RJ Jr, O'Brien JF, Katzmann JA, Peterson JM, Mann KG, Riggs BL. Concurrent assays of circulating bone Gla-protein and bone alkaline phosphatase: effects of sex, age, and metabolic bone disease. J Clin Endocrinol Metab 1988;66:951-7.
  31. Garnero P, Darte C, Delmas PD. A model to monitor the efficacy of alendronate treatment in women with osteoporosis using a biochemical marker of bone turnover. Bone 1999;24:603-9.
  32. Mücke T, Koschinski J, Deppe H, Wagenpfeil S, Pautke C, Mitchell DA, et al. Outcome of treatment and parameters influencing recurrence in patients with bisphosphonate-related osteonecrosis of the jaws. J Cancer Res Clin Oncol 2011;137:907-13.
  33. Dimopoulos MA, Kastritis E, Bamia C, Melakopoulos I, Gika D, Roussou M, et al. Reduction of osteonecrosis of the jaw (ONJ) after implementation of preventive measures in patients with multiple myeloma treated with zoledronic acid. Ann Oncol 2009;20:117-20.
  34. Ripamonti CI, Maniezzo M, Campa T, Fagnoni E, Brunelli C, Saibene G, et al. Decreased occurrence of osteonecrosis of the jaw after implementation of dental preventive measures in solid tumour patients with bone metastases treated with bisphosphonates. The experience of the National Cancer Institute of Milan. Ann Oncol 2009;20:137-45.

Cited by

  1. Genetic Investigation of Bisphosphonate-Related Osteonecrosis of Jaw (BRONJ) via Whole Exome Sequencing and Bioinformatics vol.10, pp.2, 2015, https://doi.org/10.1371/journal.pone.0118084