J Korean Assoc Oral Maxillofac Surg.  2016 Aug;42(4):193-204. 10.5125/jkaoms.2016.42.4.193.

Evaluation of the predisposing factors and involved outcome of surgical treatment in bisphosphonate-related osteonecrosis of the jaw cases including bone biopsies

Affiliations
  • 1Department of Oral and Maxillofacial Surgery, College of Dentistry, Dankook University, Cheonan, Korea. lee201@dankook.ac.kr

Abstract


OBJECTIVES
This study examined the statistical relevance of whether the systemic predisposing factors affect the prognosis of surgical treatment of bisphosphonate-related osteonecrosis of the jaw (BRONJ). All cases had undergone bone biopsies to determine the characteristics of the mechanisms of BRONJ by optical microscopy.
MATERIALS AND METHODS
The data included 54 BRONJ cases who underwent surgery and in whom bone biopsies were performed. The results of surgery were evaluated and the results were classified into 3 categories: normal recovery, delayed recovery, and recurrence after surgery. The medical history, such as diabetes mellitus, medication of steroids, malignancies on other sites was investigated for an evaluation of the systemic predisposing factors in relation to the prognosis. The three factors involved with the medication of bisphosphonate (BP) were the medication route, medication period, and drug holiday of BP before surgery. The serum C-terminal cross-linking telopeptide (CTX) value and presence of microorganism colony in bone biopsy specimens were also checked. Statistical analysis was then carried out to determine the relationship between these factors and the results of surgery.
RESULTS
The group of patients suffering from diabetes and on steroids tended to show poorer results after surgery. Parenteral medication of BP made the patients have a poorer prognosis after surgery than oral medication. In contrast, the medication period and drug holiday of BP before surgery did not have significance with the results of surgery nor did the serum CTX value and presence of microorganism colony. Necrotic bone specimens in this study typically showed disappearing new bone formation around the osteocytic lacunae and destroyed Howship's lacunae.
CONCLUSION
Although many variables exist, this study could in part, predict the prognosis of surgical treatment of BRONJ by taking the patient's medical history.

Keyword

Bisphosphonate; Osteonecrosis; Jaw diseases

MeSH Terms

Biopsy*
Bisphosphonate-Associated Osteonecrosis of the Jaw*
Causality*
Diabetes Mellitus
Holidays
Humans
Jaw Diseases
Microscopy
Osteogenesis
Osteonecrosis
Prognosis
Recurrence
Steroids
Steroids

Figure

  • Fig. 1 Distribution of surgical treatment results.

  • Fig. 2 Classification of systemic predisposing factors (medical and medication history). (DM: diabetes mellitus)

  • Fig. 3 A. Scoring system 1 calculated by adding all systemic predisposing factors. B. Scoring system 2 quotated from MUCONNS (Modified University of Connecticut Osteonecrosis Numerical Scale).

  • Fig. 4 A. Features about necrotic bone from biopsy specimen. The presence of cell components and blood vessels cannot be found and the formation of the new bones around the osteocystic lacunae are destroyed (black arrow). The boundaries adjacent to the necrotic bone sites are not smooth and show rugged feature in wavy aspects which is considered from loss of Howship's lacunae (arrowhead), and there is microorganism colony around the necrotic bone (white arrow). B. Condition around soft tissue nearby the necrotic bone. It shows typical forms of granulation tissue which include distribution of inflammatory cells and fibrosis (black arrows). Although this specimen was collected a little far from the necrotic bone, we can find microorganism colony (white arrow), and there are also bone fragments considered broken down from necrotic bone (arrowhead).

  • Fig. 5 A. Microorganism colony commonly appears not a capsular but a filamentous shape from each different stain (A: Gram staining, ×200, B: GMS staining, ×200, C: dPAS staining, ×200).


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Reference

1. McClung MR. Bisphosphonates. Endocrinol Metab Clin North Am. 2003; 32:253–271. PMID: 12699302.
Article
2. Stanton DC, Balasanian E. Outcome of surgical management of bisphosphonate-related osteonecrosis of the jaws: review of 33 surgical cases. J Oral Maxillofac Surg. 2009; 67:943–950. PMID: 19375001.
Article
3. Marx RE. Pamidronate (Aredia) and zoledronate (Zometa) induced avascular necrosis of the jaws: a growing epidemic. J Oral Maxillofac Surg. 2003; 61:1115–1117. PMID: 12966493.
Article
4. Ruggiero SL, Mehrotra B, Rosenberg TJ, Engroff SL. Osteonecrosis of the jaws associated with the use of bisphosphonates: a review of 63 cases. J Oral Maxillofac Surg. 2004; 62:527–534. PMID: 15122554.
Article
5. Hinson AM, Smith CW, Siegel ER, Stack BC Jr. Is bisphosphonate-related osteonecrosis of the jaw an infection? A histological and microbiological ten-year summary. Int J Dent. 2014; DOI: 10.1155/2014/452737.
Article
6. Ohe JY, Kwon YD, Lee HW. Bisphosphonates modulate the expression of OPG and M-CSF in hMSC-derived osteoblasts. Clin Oral Investig. 2012; 16:1153–1159.
Article
7. Kim RH, Lee RS, Williams D, Bae S, Woo J, Lieberman M, et al. Bisphosphonates induce senescence in normal human oral keratinocytes. J Dent Res. 2011; 90:810–816. PMID: 21427353.
Article
8. Kos M, Brusco D, Kuebler J, Engelke W. Clinical comparison of patients with osteonecrosis of the jaws, with and without a history of bisphosphonates administration. Int J Oral Maxillofac Surg. 2010; 39:1097–1102. PMID: 20817480.
Article
9. Lee SH, Chang SS, Lee M, Chan RC, Lee CC. Risk of osteonecrosis in patients taking bisphosphonates for prevention of osteoalsoRaporosis: a systematic review and meta-analysis. Osteoporos Int. 2014; 25:1131–1139. PMID: 24343364.
10. Khamaisi M, Regev E, Yarom N, Avni B, Leitersdorf E, Raz I, et al. Possible association between diabetes and bisphosphonate-related jaw osteonecrosis. J Clin Endocrinol Metab. 2007; 92:1172–1175. PMID: 17179196.
Article
11. Sung EC, Chan SM, Sakurai K, Chung E. Osteonecrosis of the maxilla as a complication to chemotherapy: a case report. Spec Care Dentist. 2002; 22:142–146. PMID: 12449457.
Article
12. Tarassoff P, Csermak K. Avascular necrosis of the jaws: risk factors in metastatic cancer patients. J Oral Maxillofac Surg. 2003; 61:1238–1239. PMID: 14586868.
Article
13. Migliorati CA, Schubert MM, Peterson DE, Seneda LM. Bisphosphonate-associated osteonecrosis of mandibular and maxillary bone: an emerging oral complication of supportive cancer therapy. Cancer. 2005; 104:83–93. PMID: 15929121.
14. Hewitt C, Farah CS. Bisphosphonate-related osteonecrosis of the jaws: a comprehensive review. J Oral Pathol Med. 2007; 36:319–328. PMID: 17559492.
Article
15. Leite AF, Figueiredo PT, Melo NS, Acevedo AC, Cavalcanti MG, Paula LM, et al. Bisphosphonate-associated osteonecrosis of the jaws. Report of a case and literature review. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2006; 102:14–21. PMID: 16831667.
Article
16. Marx RE, Cillo JE Jr, Ulloa JJ. Oral bisphosphonate-induced osteonecrosis: risk factors, prediction of risk using serum CTX testing, prevention, and treatment. J Oral Maxillofac Surg. 2007; 65:2397–2410. PMID: 18022461.
Article
17. Freiberger JJ, Padilla-Burgos R, Chhoeu AH, Kraft KH, Boneta O, Moon RE, et al. Hyperbaric oxygen treatment and bisphosphonate-induced osteonecrosis of the jaw: a case series. J Oral Maxillofac Surg. 2007; 65:1321–1327. PMID: 17577496.
Article
18. Vescovi P, Merigo E, Meleti M, Manfredi M. Bisphosphonate-associated osteonecrosis (BON) of the jaws: a possible treatment? J Oral Maxillofac Surg. 2006; 64:1460–1462. PMID: 16916694.
Article
19. Lopes RN, Rabelo GD, Rocha AC, Carvalho PA, Alves FA. Surgical therapy for bisphosphonate-related osteonecrosis of the jaw: six-year experience of a single institution. J Oral Maxillofac Surg. 2015; 73:1288–1295. PMID: 25871903.
Article
20. Stockmann P, Burger M, von Wilmowsky C, Ebker T, Lutz R, Bauersachs A, et al. 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; 18:1299–1304.
21. 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. PMID: 19371819.
Article
22. Reich W, Bilkenroth U, Schubert J, Wickenhauser C, Eckert AW. Surgical treatment of bisphosphonate-associated osteonecrosis: Prognostic score and long-term results. J Craniomaxillofac Surg. 2015; 43:1809–1822. PMID: 26321065.
Article
23. Kim KW, Kim BJ, Lee CH. Clinical study of diagnosis and treatment of bisphosphonate-related osteonecrosis of the jaws. J Korean Assoc Oral Maxillofac Surg. 2011; 37:54–61.
Article
24. Lehenkari PP, Kellinsalmi M, Näpänkangas JP, Ylitalo KV, Mönkkönen J, Rogers MJ, et al. Further insight into mechanism of action of clodronate: inhibition of mitochondrial ADP/ATP translocase by a nonhydrolyzable, adenine-containing metabolite. Mol Pharmacol. 2002; 61:1255–1262. PMID: 11961144.
Article
25. Molcho S, Peer A, Berg T, Futerman B, Khamaisi M. Diabetes microvascular disease and the risk for bisphosphonate-related osteonecrosis of the jaw: a single center study. J Clin Endocrinol Metab. 2013; 98:E1807–E1812. PMID: 24037883.
Article
26. Watters AL, Hansen HJ, Williams T, Chou JF, Riedel E, Halpern J, et al. Intravenous bisphosphonate-related osteonecrosis of the jaw: long-term follow-up of 109 patients. Oral Surg Oral Med Oral Pathol Oral Radiol. 2013; 115:192–200. PMID: 23036797.
Article
27. Favus MJ. Diabetes and the risk of osteonecrosis of the jaw. J Clin Endocrinol Metab. 2007; 92:817–818. PMID: 17341579.
Article
28. Ichiseki T, Ueda Y, Katsuda S, Kitamura K, Kaneuji A, Matsumoto T. Oxidative stress by glutathione depletion induces osteonecrosis in rats. Rheumatology (Oxford). 2006; 45:287–290. PMID: 16303823.
Article
29. 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; 46:664–668. PMID: 17562443.
Article
30. Vieillard MH, Maes JM, Penel G, Facon T, Magro L, Bonneterre J, et al. Thirteen cases of jaw osteonecrosis in patients on bisphosphonate therapy. Joint Bone Spine. 2008; 75:34–40. PMID: 17981488.
Article
31. Kos M, Kuebler JF, Luczak K, Engelke W. Bisphosphonate-related osteonecrosis of the jaws: a review of 34 cases and evaluation of risk. J Craniomaxillofac Surg. 2010; 38:255–259. PMID: 19592261.
Article
32. Brown JE, Cook RJ, Major P, Lipton A, Saad F, Smith M, et al. Bone turnover markers as predictors of skeletal complications in prostate cancer, lung cancer, and other solid tumors. J Natl Cancer Inst. 2005; 97:59–69. PMID: 15632381.
Article
33. Garnero P, Delmas PD. Noninvasive techniques for assessing skeletal changes in inflammatory arthritis: bone biomarkers. Curr Opin Rheumatol. 2004; 16:428–434. PMID: 15201607.
34. Fleisher KE, Welch G, Kottal S, Craig RG, Saxena D, Glickman RS. Predicting risk for bisphosphonate-related osteonecrosis of the jaws: CTX versus radiographic markers. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2010; 110:509–516. PMID: 20674404.
Article
35. Kunchur R, Need A, Hughes T, Goss A. Clinical investigation of C-terminal cross-linking telopeptide test in prevention and management of bisphosphonate-associated osteonecrosis of the jaws. J Oral Maxillofac Surg. 2009; 67:1167–1173. PMID: 19446200.
Article
36. American Society for Bone and Mineral Research Task Force on Osteonecrosis of the Jaw. Khosla S, Burr D, Cauley J, Dempster DW, Ebeling PR, et al. Oral bisphosphonate-induced osteonecrosis: risk factors, prediction of risk using serum CTX testing, prevention, and treatment. J Oral Maxillofac Surg. 2008; 66:1320–1321. author reply 1321-2. PMID: 18486811.
Article
37. Berger CE, Kröner A, Kristen KH, Minai-Pour M, Leitha T, Engel A. Spontaneous osteonecrosis of the knee: biochemical markers of bone turnover and pathohistology. Osteoarthritis Cartilage. 2005; 13:716–721. PMID: 15922633.
Article
38. Ganguli A, Steward C, Butler SL, Philips GJ, Meikle ST, Lloyd AW, et al. Bacterial adhesion to bisphosphonate coated hydroxyapatite. J Mater Sci Mater Med. 2005; 16:283–287. PMID: 15803271.
Article
39. Kos M, Junka A, Smutnicka D, Bartoszewicz M, Kurzynowski T, Gluza K. Pamidronate enhances bacterial adhesion to bone hydroxyapatite. Another puzzle in the pathology of bisphosphonate-related osteonecrosis of the jaw? J Oral Maxillofac Surg. 2013; 71:1010–1016. PMID: 23489958.
Article
40. Anavi-Lev K, Anavi Y, Chaushu G, Alon DM, Gal G, Kaplan I. Bisphosphonate related osteonecrosis of the jaws: clinico-pathological investigation and histomorphometric analysis. Oral Surg Oral Med Oral Pathol Oral Radiol. 2013; 115:660–666. PMID: 23601221.
Article
41. Hansen T, Kunkel M, Springer E, Walter C, Weber A, Siegel E, et al. Actinomycosis of the jaws--histopathological study of 45 patients shows significant involvement in bisphosphonate-associated osteonecrosis and infected osteoradionecrosis. Virchows Arch. 2007; 451:1009–1017. PMID: 17952459.
Article
42. Naik NH, Russo TA. Bisphosphonate-related osteonecrosis of the jaw: the role of actinomyces. Clin Infect Dis. 2009; 49:1729–1732. PMID: 19886792.
Article
43. Kumar SK, Gorur A, Schaudinn C, Shuler CF, Costerton JW, Sedghizadeh PP. The role of microbial biofilms in osteonecrosis of the jaw associated with bisphosphonate therapy. Curr Osteoporos Rep. 2010; 8:40–48. PMID: 20425090.
Article
44. Sedghizadeh PP, Yooseph S, Fadrosh DW, Zeigler-Allen L, Thiagarajan M, Salek H, et al. Metagenomic investigation of microbes and viruses in patients with jaw osteonecrosis associated with bisphosphonate therapy. Oral Surg Oral Med Oral Pathol Oral Radiol. 2012; 114:764–770. PMID: 23159114.
Article
45. Marx RE, Tursun R. Suppurative osteomyelitis, bisphosphonate induced osteonecrosis, osteoradionecrosis: a blinded histopathologic comparison and its implications for the mechanism of each disease. Int J Oral Maxillofac Surg. 2012; 41:283–289. PMID: 22244079.
Article
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