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The association between the severity of periodontitis and osteonecrosis of the jaw in patients with different cancer locations: a nationwide population-based study

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Abstract

Objectives

To determine the relation between the severity of periodontitis and osteonecrosis of the jaw (ONJ) occurrence among different cancer locations and estimate the effect of dental care on ONJ prevention in cancer patients.

Materials and methods

This population-based cross-sectional study was conducted through the Longitudinal Health Insurance Database, Taiwan. Patients with malignancies were collected and subdivided into groups according to their different cancer locations, the severity of periodontitis, and dental care. Multivariable logistic regression analysis was performed to assess the associations between ONJ and ONJ-related factors.

Results

A total of 8,234 ONJ patients and 32,912 control patients were investigated. Lip, oral cavity, and pharynx malignancies had the highest ONJ risk among all cancer locations (OR from 3.07 to 9.56, P < 0.01). There is a linear relationship between different severities of periodontitis and ONJ. Patients with radiotherapy and severe periodontitis had the highest ONJ risk (adjusted OR, 9.56; 95% CI, 5.34–17.1). Patients with good dental care had a lower ONJ risk.

Conclusions

The periodontal condition and cancer location showed a significant impact on the risk of developing ONJ after adjusting for bisphosphonate use. Good dental care could decrease the risk of ONJ in cancer patients. The severity of periodontitis might be a target to predict the potency of ONJ.

Clinical relevance

Dentists must be vigilant about the increased risk of ONJ in cancer patients with periodontitis, especially in the head and neck cancer population. Good dental care is advised for cancer patients with severe periodontitis.

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References

  1. Baldi D, Izzotti A, Bonica P, Pera P, Pulliero A (2009) Degenerative periodontal-diseases and oral osteonecrosis: the role of gene-environment interactions. Mutat Res 667:118–131. https://doi.org/10.1016/j.mrfmmm.2008.11.005

    Article  PubMed  Google Scholar 

  2. Khan AA, Morrison A, 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, Al Dabagh R, Davison KS, Kendler DL, Sandor GK, Josse RG, Bhandari M, El Rabbany M, Pierroz DD, Sulimani R, Saunders DP, Brown JP, Compston J and International Task Force on Osteonecrosis of the J (2015) Diagnosis and management of osteonecrosis of the jaw: a systematic review and international consensus. J Bone Miner Res 30:3–23. https://doi.org/10.1002/jbmr.2405

    Article  PubMed  Google Scholar 

  3. Miksad RA, Lai KC, Dodson TB, Woo SB, Treister NS, Akinyemi O, Bihrle M, Maytal G, August M, Gazelle GS, Swan JS (2011) Quality of life implications of bisphosphonate-associated osteonecrosis of the jaw. Oncologist 16:121–132. https://doi.org/10.1634/theoncologist.2010-0183

    Article  PubMed  PubMed Central  Google Scholar 

  4. Eke PI, Dye BA, Wei L, Thornton-Evans GO, Genco RJ, Surveillance CPD, workgroup: James Beck GDRP (2012) Prevalence of periodontitis in adults in the United States: 2009 and 2010. J Dent Res 91:914–920. https://doi.org/10.1177/0022034512457373

    Article  PubMed  Google Scholar 

  5. Aguirre JI, Akhter MP, Kimmel DB, Pingel JE, Williams A, Jorgensen M, Kesavalu L, Wronski TJ (2012) Oncologic doses of zoledronic acid induce osteonecrosis of the jaw-like lesions in rice rats (Oryzomys palustris) with periodontitis. J Bone Miner Res 27:2130–2143. https://doi.org/10.1002/jbmr.1669

    Article  PubMed  Google Scholar 

  6. Pushalkar S, Li X, Kurago Z, Ramanathapuram LV, Matsumura S, Fleisher KE, Glickman R, Yan W, Li Y, Saxena D (2014) Oral microbiota and host innate immune response in bisphosphonate-related osteonecrosis of the jaw. Int J Oral Sci 6:219–226. https://doi.org/10.1038/ijos.2014.46

    Article  PubMed  PubMed Central  Google Scholar 

  7. Marx RE, Sawatari Y, Fortin M, Broumand V (2005) Bisphosphonate-induced exposed bone (osteonecrosis/osteopetrosis) of the jaws: risk factors, recognition, prevention, and treatment. J Oral Maxillofac Surg 63:1567–1575. https://doi.org/10.1016/j.joms.2005.07.010

    Article  PubMed  Google Scholar 

  8. Vahtsevanos K, Kyrgidis A, Verrou E, Katodritou E, Triaridis S, Andreadis CG, Boukovinas I, Koloutsos GE, Teleioudis Z, Kitikidou K, Paraskevopoulos P, Zervas K, Antoniades K (2009) Longitudinal cohort study of risk factors in cancer patients of bisphosphonate-related osteonecrosis of the jaw. Journal of clinical oncology : official journal of the American Society of Clinical Oncology 27:5356–5362. https://doi.org/10.1200/JCO.2009.21.9584

    Article  Google Scholar 

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

    Article  Google Scholar 

  10. Kos M, Brusco D, Kuebler J, Engelke W (2010) Clinical comparison of patients with osteonecrosis of the jaws, with and without a history of bisphosphonates administration. Int J Oral Maxillofac Surg 39:1097–1102. https://doi.org/10.1016/j.ijom.2010.04.054

    Article  PubMed  Google Scholar 

  11. Yamazaki T, Yamori M, Ishizaki T, Asai K, Goto K, Takahashi K, Nakayama T, Bessho K (2012) Increased incidence of osteonecrosis of the jaw after tooth extraction in patients treated with bisphosphonates: a cohort study. Int J Oral Maxillofac Surg 41:1397–1403. https://doi.org/10.1016/j.ijom.2012.06.020

    Article  PubMed  Google Scholar 

  12. Pavkovic M, Petrushevska G, Jovanovic R, Karanfilski O, Cevreska L, Stankovic S, Stojanovic A (2010) Osteonecrosis of the jaw in patients with multiple myeloma treated with bisphosphanates. Prilozi 31:39–49

    PubMed  Google Scholar 

  13. Guarneri V, Miles D, Robert N, Dieras V, Glaspy J, Smith I, Thomssen C, Biganzoli L, Taran T, Conte P (2010) Bevacizumab and osteonecrosis of the jaw: incidence and association with bisphosphonate therapy in three large prospective trials in advanced breast cancer. Breast Cancer Res Treat 122:181–188. https://doi.org/10.1007/s10549-010-0866-3

    Article  PubMed  Google Scholar 

  14. Tennis P, Rothman KJ, Bohn RL, Tan H, Zavras A, Laskarides C, Calingaert B, Anthony MS (2012) Incidence of osteonecrosis of the jaw among users of bisphosphonates with selected cancers or osteoporosis. Pharmacoepidemiol Drug Saf 21:810–817. https://doi.org/10.1002/pds.3292

    Article  PubMed  Google Scholar 

  15. Gabbert TI, Hoffmeister B, Felsenberg D (2015) Risk factors influencing the duration of treatment with bisphosphonates until occurrence of an osteonecrosis of the jaw in 963 cancer patients. J Cancer Res Clin Oncol 141:749–758. https://doi.org/10.1007/s00432-014-1853-6

    Article  PubMed  Google Scholar 

  16. Huang YF, Liu SP, Muo CH, Tsai CH, Chang CT (2020) The association between dental therapy timelines and osteoradionecrosis: a nationwide population-based cohort study. Clin Oral Investig 24:455–463. https://doi.org/10.1007/s00784-019-02866-4

    Article  PubMed  Google Scholar 

  17. Huang YF, Chang CT, Liu SP, Muo CH, Tsai CH, Hong HH, Shen YF, Wu CZ (2016) The impact of oral hygiene maintenance on the association between periodontitis and osteoporosis: a nationwide population-based cross sectional study. Medicine (Baltimore) 95:e2348. https://doi.org/10.1097/MD.0000000000002348

    Article  PubMed Central  Google Scholar 

  18. Khamaisi M, Regev E, Yarom N, Avni B, Leitersdorf E, Raz I, Elad S (2007) Possible association between diabetes and bisphosphonate-related jaw osteonecrosis. J Clin Endocrinal Metabol 92:1172–1175. https://doi.org/10.1210/jc.2006-2036

    Article  Google Scholar 

  19. Huang YF, Chang CT, Muo CH, Tsai CH, Shen YF, Wu CZ (2015) Impact of bisphosphonate-related osteonecrosis of the jaw on osteoporotic patients after dental extraction: a population-based cohort study. PLoS ONE 10:e0120756. https://doi.org/10.1371/journal.pone.0120756

    Article  PubMed  PubMed Central  Google Scholar 

  20. King AE, Umland EM (2008) Osteonecrosis of the jaw in patients receiving intravenous or oral bisphosphonates. Pharmacotherapy 28:667–677. https://doi.org/10.1592/phco.28.5.667

    Article  PubMed  Google Scholar 

  21. Yarom N, Yahalom R, Shoshani Y, Hamed W, Regev E, Elad S (2007) Osteonecrosis of the jaw induced by orally administered bisphosphonates: incidence, clinical features, predisposing factors and treatment outcome. Osteoporos Int 18:1363–1370. https://doi.org/10.1007/s00198-007-0384-2

    Article  PubMed  Google Scholar 

  22. Walter C, Al-Nawas B, Frickhofen N, Gamm H, Beck J, Reinsch L, Blum C, Grotz KA, Wagner W (2010) Prevalence of bisphosphonate associated osteonecrosis of the jaws in multiple myeloma patients. Head Face Med 6:11. https://doi.org/10.1186/1746-160X-6-11

    Article  PubMed  PubMed Central  Google Scholar 

  23. Francini F, Pascucci A, Francini E, Miano ST, Bargagli G, Ruggiero G, Petrioli R (2011) Osteonecrosis of the jaw in patients with cancer who received zoledronic acid and bevacizumab. J Am Dent Assoc 142:506–513

    Article  Google Scholar 

  24. Walter C, Al-Nawas B, Grotz KA, Thomas C, Thuroff JW, Zinser V, Gamm H, Beck J, Wagner W (2008) Prevalence and risk factors of bisphosphonate-associated osteonecrosis of the jaw in prostate cancer patients with advanced disease treated with zoledronate. Eur Urol 54:1066–1072. https://doi.org/10.1016/j.eururo.2008.06.070

    Article  PubMed  Google Scholar 

  25. Hinchy NV, Jayaprakash V, Rossitto RA, Anders PL, Korff KC, Canallatos P, Sullivan MA (2013) Osteonecrosis of the jaw - prevention and treatment strategies for oral health professionals. Oral Oncol 49:878–886. https://doi.org/10.1016/j.oraloncology.2013.06.008

    Article  PubMed  Google Scholar 

  26. Andersen TL, Boissy P, Sondergaard TE, Kupisiewicz K, Plesner T, Rasmussen T, Haaber J, Kolvraa S, Delaisse JM (2007) Osteoclast nuclei of myeloma patients show chromosome translocations specific for the myeloma cell clone: a new type of cancer-host partnership? J Pathol 211:10–17. https://doi.org/10.1002/path.2078

    Article  PubMed  Google Scholar 

  27. Badros A, Terpos E, Katodritou E, Goloubeva O, Kastritis E, Verrou E, Zervas K, Baer MR, Meiller T, Dimopoulos MA (2008) Natural history of osteonecrosis of the jaw in patients with multiple myeloma. J Clin Oncol Off J Amer Soc Clin Oncol 26:5904–5909. https://doi.org/10.1200/JCO.2008.16.9300

    Article  Google Scholar 

  28. Guise TA (2000) Molecular mechanisms of osteolytic bone metastases. Cancer 88:2892–2898

    Article  Google Scholar 

  29. Rodrigues P, Hering F, Imperio M (2015) Safety of I.v. Nonnitrogen bisphosphonates on the occurrence of osteonecrosis of the jaw: long-term follow-up on prostate cancer patients. Clin Genitourin Cancer 13:199–203. https://doi.org/10.1016/j.clgc.2014.10.001

    Article  PubMed  Google Scholar 

  30. Campisi G, Fedele S, Fusco V, Pizzo G, Di Fede O, Bedogni A (2014) Epidemiology, clinical manifestations, risk reduction and treatment strategies of jaw osteonecrosis in cancer patients exposed to antiresorptive agents. Future Oncol 10:257–275. https://doi.org/10.2217/fon.13.211

    Article  PubMed  Google Scholar 

  31. Thorn JJ, Hansen HS, Specht L and Bastholt L (2000) Osteoradionecrosis of the jaws: clinical characteristics and relation to the field of irradiation. J Oral Maxillofac Surg 58:1088–93; discussion 1093–5. https://doi.org/10.1053/joms.2000.9562

  32. Berenson JR, Lichtenstein A, Porter L, Dimopoulos MA, Bordoni R, George S, Lipton A, Keller A, Ballester O, Kovacs MJ, Blacklock HA, Bell R, Simeone J, Reitsma DJ, Heffernan M, Seaman J, Knight RD (1996) Efficacy of pamidronate in reducing skeletal events in patients with advanced multiple myeloma. Myeloma Aredia Study Group. N Engl J Med 334:488–493. https://doi.org/10.1056/nejm199602223340802

    Article  PubMed  Google Scholar 

  33. Kyle RA, Yee GC, Somerfield MR, Flynn PJ, Halabi S, Jagannath S, Orlowski RZ, Roodman DG, Twilde P, Anderson K and American Society of Clinical O (2007) American Society of Clinical Oncology 2007 clinical practice guideline update on the role of bisphosphonates in multiple myeloma. J Clin Oncol Off J Amer Soc Clin Oncol 25:2464–2472. https://doi.org/10.1200/JCO.2007.12.1269

  34. Tsao C, Darby I, Ebeling PR, Walsh K, O’Brien-Simpson N, Reynolds E, Borromeo G (2013) Oral health risk factors for bisphosphonate-associated jaw osteonecrosis. J Oral Maxillofac Surg 71:1360–1366. https://doi.org/10.1016/j.joms.2013.02.016

    Article  PubMed  Google Scholar 

  35. Thumbigere-Math V, Michalowicz BS, Hodges JS, Tsai ML, Swenson KK, Rockwell L, Gopalakrishnan R (2014) Periodontal disease as a risk factor for bisphosphonate-related osteonecrosis of the jaw. J Periodontol 85:226–233. https://doi.org/10.1902/jop.2013.130017

    Article  PubMed  Google Scholar 

  36. Listgarten MA (1980) Periodontal probing: what does it mean? J Clin Periodontol 7:165–176

    Article  Google Scholar 

  37. Periodontology TAAo, (2000) Parameter on periodontal maintenance. American Academy of Periodontology J Periodontol 71:849–850. https://doi.org/10.1902/jop.2000.71.5-S.849

    Article  Google Scholar 

  38. Sroussi HY, Epstein JB, Bensadoun RJ, Saunders DP, Lalla RV, Migliorati CA, Heaivilin N, Zumsteg ZS (2017) Common oral complications of head and neck cancer radiation therapy: mucositis, infections, saliva change, fibrosis, sensory dysfunctions, dental caries, periodontal disease, and osteoradionecrosis. Cancer Med 6:2918–2931. https://doi.org/10.1002/cam4.1221

    Article  PubMed  PubMed Central  Google Scholar 

  39. Lambade PN, Lambade D, Goel M (2013) Osteoradionecrosis of the mandible: a review. Oral Maxillofac Surg 17:243–249. https://doi.org/10.1007/s10006-012-0363-4

    Article  PubMed  Google Scholar 

  40. Krimmel M, Ripperger J, Hairass M, Hoefert S, Kluba S, Reinert S (2014) Does dental and oral health influence the development and course of bisphosphonate-related osteonecrosis of the jaws (BRONJ)? Oral Maxillofac Surg 18:213–218. https://doi.org/10.1007/s10006-013-0408-3

    Article  PubMed  Google Scholar 

  41. Lee SH, Chan RC, Chang SS, Tan YL, Chang KH, Lee MC, Chang HE, Lee CC (2014) Use of bisphosphonates and the risk of osteonecrosis among cancer patients: a systemic review and meta-analysis of the observational studies. Support Care Cancer 22:553–560. https://doi.org/10.1007/s00520-013-2017-y

    Article  PubMed  Google Scholar 

  42. Vandone AM, Donadio M, Mozzati M, Ardine M, Polimeni MA, Beatrice S, Ciuffreda L, Scoletta M (2012) Impact of dental care in the prevention of bisphosphonate-associated osteonecrosis of the jaw: a single-center clinical experience. Ann Oncology Off J Euro Soc Med Oncol (ESMO) 23:193–200. https://doi.org/10.1093/annonc/mdr039

    Article  Google Scholar 

  43. Dei F, Taglieri L, Amoroso L, Vendittozzi S, Blasi L, Salerno G, Lanza R, Scarpa S (2014) Prevention of osteonecrosis of the jaw in patients with bone metastases treated with bisphosphonates. Anticancer Res 34:2477–2480

    Google Scholar 

  44. Scully C, Madrid C, Bagan J (2006) Dental endosseous implants in patients on bisphosphonate therapy. Implant Dent 15:212–218. https://doi.org/10.1097/01.id.0000236120.22719.02

    Article  PubMed  Google Scholar 

  45. Weitzman R, Sauter N, Eriksen EF, Tarassoff PG, Lacerna LV, Dias R, Altmeyer A, Csermak-Renner K, McGrath L, Lantwicki L, Hohneker JA (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 62:148–152. https://doi.org/10.1016/j.critrevonc.2006.12.005

    Article  PubMed  Google Scholar 

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Funding

This study was supported in part by the Ministry of Health and Welfare, Taiwan (MOHW109-TDU-B-212–114004), Ministry of Science and Technology, Taiwan (MOST 110-2314-B-182A-040), MOST Clinical Trial Consortium for Stroke (MOST 109–2321-B-039–002), China Medical University Hospital (DMR-109–126), Chang Gung Memorial Hospital, Linkou, Taiwan (CMRPG3L0051), Far Eastern Memorial Hospital (FEMH-2021-C-051), and Tseng-Lien Lin Foundation, Taichung, Taiwan (MOHW-M07B4079, Poh-Ai-10703).

Author information

Authors and Affiliations

  1. Department of General Dentistry, Chang Gung Memorial Hospital, Linkou, 33305, Taiwan

    Yi-Fang Huang

  2. School of Dentistry, College of Oral Medicine, Taipei Medical University, No. 250, Wu-Hsing St., Xinyi Dist, Taipei, 11031, Taiwan

    Yi-Fang Huang, Kuan-Chou Lin, Chung-Ta Chang, Po-Jen Chang & Ching-Zong Wu

  3. Graduate Institute of Dental and Craniofacial Science, College of Medicine, Chang Gung University, Taoyuan, 33302, Taiwan

    Yi-Fang Huang

  4. Department of Oral and Maxillofacial Surgery, Wan Fang Hospital, Taipei Medical University, Taipei, 11696, Taiwan

    Kuan-Chou Lin

  5. Graduate Institute of Basic Medical Science, China Medical University, Taichung, 40402, Taiwan

    Shih-Ping Liu

  6. Center for Neuropsychiatry, China Medical University Hospital, Taichung, 40402, Taiwan

    Shih-Ping Liu

  7. Department of Social Work, Asia University, Taichung, 41354, Taiwan

    Shih-Ping Liu

  8. Department of Emergency Medicine, Far Eastern Memorial Hospital, Taipei, 22056, Taiwan

    Chung-Ta Chang

  9. Graduate Institute of Medicine, Yuan Ze University, Taoyuan, 32003, Taiwan

    Chung-Ta Chang

  10. Management Office for Health Data, China Medical University Hospital, Taichung, 40402, Taiwan

    Chih-Hsin Muo

  11. Graduate Institute of Clinical Medicine, China Medical University, Taichung, 40402, Taiwan

    Chun-Hao Tsai

  12. Department of Orthopedics, China Medical University Hospital, Taichung, 40402, Taiwan

    Chun-Hao Tsai

  13. Department of Dentistry, Taipei Medical University Hospital, Taipei, 11031, Taiwan

    Ching-Zong Wu

  14. Department of Dentistry, Lotung Poh-Ai Hospital, Yilan, 26546, Taiwan

    Ching-Zong Wu

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  1. Yi-Fang Huang
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  2. Kuan-Chou Lin
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  5. Chih-Hsin Muo
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  7. Chun-Hao Tsai
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Correspondence to Ching-Zong Wu.

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Huang, YF., Lin, KC., Liu, SP. et al. The association between the severity of periodontitis and osteonecrosis of the jaw in patients with different cancer locations: a nationwide population-based study. Clin Oral Invest 26, 3843–3852 (2022). https://doi.org/10.1007/s00784-021-04175-1

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