[go: up one dir, main page]

Skip to main content

Advertisement

Log in

Pain characteristics in medication-related osteonecrosis of the jaws

  • Original Article
  • Published:
Supportive Care in Cancer Aims and scope Submit manuscript

Abstract

Purpose

To characterise pain from medication-related osteonecrosis of the jaws (MRONJ) and the effects of antimicrobial treatment on it.

Methods

Data from files of patients diagnosed with MRONJ according to the position paper of the American Association of Oral and Maxillofacial Surgeons (2014) and Multinational Association of Supportive Care in Cancer and American Society of Clinical Oncology (2019) were collected retrospectively, including gender, age, primary disease, bone-modifying agents (BMAs)/anti-angiogenics, administration route, involved jaw, location, and exposure size. The patients were treated according to the abovementioned position papers’ recommendations, i.e. all patients who suffered from pain were staged as 2 or 3 and treated with systemic amoxicillin, or doxycycline or clindamycin in case of sensitivity, and local antiseptic and hygiene instructions.

Results

Data from 77 MRONJ patients (aged 65.09 ± 11.9 years old) were analysed. Most (90.1%) received bisphosphonates for cancer (79%) and osteoporosis (17%). A total of 67.5% experienced pain; 36.5% had moderate-to-severe pain. Female gender was significantly associated with the presence of pain (p = 0.002). Osteonecrosis lesions after dento-alveolar surgery had a higher risk of pain development than spontaneous lesions (p = 0.045). Medical and oncologic background, type of pharmacotherapy, lesion size, and location were not associated with pain levels. Worse initial pain was significantly associated with better relief following MRONJ treatment (p = 0.045). Meaningful pain reduction ( 50%) was significantly correlated with initial pain severity (p = 0.0128, OR = 4.75).

Conclusions

Pain from infection and inflammation often accompanies MRONJ. The presence of pain is correlated with longer BMAs pre-therapy and if surgery preceded the MRONJ. Persistency of the mild pain together with a resistance to common antimicrobial treatment, although not complete, is a feature that MRONJ pain shares with neuropathic-“like” pain, and requires further study and consideration during treatment.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Subscribe and save

Springer+ Basic
$34.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or eBook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Ruggiero SL, Dodson TB, Fantasia J, Goodday R, Aghaloo T, Mehrotra B, O'Ryan F, American Association of O, Maxillofacial S (2014) American Association of Oral and Maxillofacial Surgeons position paper on medication-related osteonecrosis of the jaw-2014 update. J Oral Maxillofac Surg 72(10):1938–1956. https://doi.org/10.1016/j.joms.2014.04.031

    Article  PubMed  Google Scholar 

  2. Zeevi I, Anavi Y, Kaplan I, Zadik Y (2013) Jaws features in type 1 Gaucher disease. J Oral Maxillofac Surg 71(4):694–701. https://doi.org/10.1016/j.joms.2012.09.020

    Article  PubMed  Google Scholar 

  3. Yarom N, Shapiro CL, Peterson DE, Van Poznak CH, Bohlke K, Ruggiero SL, Migliorati CA, Khan A, Morrison A, Anderson H, Murphy BA, Alston-Johnson D, Mendes RA, Beadle BM, Jensen SB, Saunders DP (2019) Medication-related osteonecrosis of the jaw: MASCC/ISOO/ASCO Clinical Practice Guideline. J Clin Oncol 37(25):2270–2290. https://doi.org/10.1200/JCO.19.01186

    Article  PubMed  Google Scholar 

  4. Woo SB, Hellstein JW, Kalmar JR (2006) Narrative [corrected] review: bisphosphonates and osteonecrosis of the jaws. Ann Intern Med 144(10):753–761. https://doi.org/10.7326/0003-4819-144-10-200605160-00009

    Article  PubMed  CAS  Google Scholar 

  5. Srinivasan D, Shetty S, Ashworth D, Grew N, Millar B (2007) Orofacial pain-a presenting symptom of bisphosphonate associated osteonecrosis of the jaws. Br Dent J 203(2):91–92. https://doi.org/10.1038/bdj.2007.635

    Article  PubMed  CAS  Google Scholar 

  6. Ruggiero SL, Woo SB (2008) Biophosphonate-related osteonecrosis of the jaws. Dent Clin N Am 52(1):111–128, ix. https://doi.org/10.1016/j.cden.2007.09.002

    Article  PubMed  Google Scholar 

  7. Lerman MA, Xie W, Treister NS, Richardson PG, Weller EA, Woo SB (2013) Conservative management of bisphosphonate-related osteonecrosis of the jaws: staging and treatment outcomes. Oral Oncol 49(9):977–983. https://doi.org/10.1016/j.oraloncology.2013.05.012

    Article  PubMed  CAS  Google Scholar 

  8. Assael LA (2009) Oral bisphosphonates as a cause of bisphosphonate-related osteonecrosis of the jaws: clinical findings, assessment of risks, and preventive strategies. J Oral Maxillofac Surg 67(5 Suppl):35–43. https://doi.org/10.1016/j.joms.2009.01.003

    Article  PubMed  Google Scholar 

  9. Elad S, Gomori MJ, Ben-Ami N, Friedlander-Barenboim S, Regev E, Lazarovici TS, Yarom N (2010) Bisphosphonate-related osteonecrosis of the jaw: clinical correlations with computerized tomography presentation. Clin Oral Investig 14(1):43–50. https://doi.org/10.1007/s00784-009-0311-3

    Article  PubMed  Google Scholar 

  10. Otto S, Hafner S, Grotz KA (2009) The role of inferior alveolar nerve involvement in bisphosphonate-related osteonecrosis of the jaw. J Oral Maxillofac Surg 67(3):589–592. https://doi.org/10.1016/j.joms.2008.09.028

    Article  PubMed  Google Scholar 

  11. Zadik Y, Benoliel R, Fleissig Y, Casap N (2012) Painful trigeminal neuropathy induced by oral bisphosphonate-related osteonecrosis of the jaw: a new etiology for the numb-chin syndrome. Quintessence Int 43(2):97–104

    PubMed  Google Scholar 

  12. Poon P, Jackson K, Platt T (2010) When managing established osteonecrosis of the jaw, don't forget the not-infrequent chronic refractory pain. Intern Med J 40(3):243–244. https://doi.org/10.1111/j.1445-5994.2010.02166.x

    Article  PubMed  CAS  Google Scholar 

  13. Fedele S, Porter SR, D'Aiuto F, Aljohani S, Vescovi P, Manfredi M, Arduino PG, Broccoletti R, Musciotto A, Di Fede O, Lazarovici TS, Campisi G, Yarom N (2010) Nonexposed variant of bisphosphonate-associated osteonecrosis of the jaw: a case series. Am J Med 123(11):1060–1064. https://doi.org/10.1016/j.amjmed.2010.04.033

    Article  PubMed  CAS  Google Scholar 

  14. Allen MR, Ruggiero SL (2014) A review of pharmaceutical agents and oral bone health: how osteonecrosis of the jaw has affected the field. Int J Oral Maxillofac Implants 29(1):e45–e57. https://doi.org/10.11607/jomi.te41

    Article  PubMed  Google Scholar 

  15. Naik NH, Russo TA (2009) Bisphosphonate-related osteonecrosis of the jaw: the role of actinomyces. Clin Infect Dis 49(11):1729–1732. https://doi.org/10.1086/648075

    Article  PubMed  Google Scholar 

  16. Raffa RBLR, Pergolizzi JV, Porreca F, Tallarida RJ (2012b) Chemotherapy-induced neuropathic pain. Orofacial neuropathy and pain in cancer patients. CRC Press

  17. Abdalla-Aslan R, Benoliel R, Sharav Y, Czerninski R (2016) Characterization of pain originating from oral mucosal lesions. Oral Surg Oral Med Oral Pathol Oral Radiol 121(3):255–261. https://doi.org/10.1016/j.oooo.2015.11.006

    Article  PubMed  Google Scholar 

  18. Sharav YBR (2015) Orofacial pain and headache. Acute orofacial pain, 2nd edn. Quintessence Publishing Co, USA

    Google Scholar 

  19. Fusco V, Santini D, Armento G, Tonini G, Campisi G (2016) Osteonecrosis of jaw beyond antiresorptive (bone-targeted) agents: new horizons in oncology. Expert Opin Drug Saf 15(7):925–935. https://doi.org/10.1080/14740338.2016.1177021

    Article  PubMed  CAS  Google Scholar 

  20. Paller CJ, Campbell CM, Edwards RR, Dobs AS (2009) Sex-based differences in pain perception and treatment. Pain Med 10(2):289–299. https://doi.org/10.1111/j.1526-4637.2008.00558.x

    Article  PubMed  PubMed Central  Google Scholar 

  21. Popescu A, LeResche L, Truelove EL, Drangsholt MT (2010) Gender differences in pain modulation by diffuse noxious inhibitory controls: a systematic review. Pain 150(2):309–318. https://doi.org/10.1016/j.pain.2010.05.013

    Article  PubMed  Google Scholar 

  22. Goffaux P, Michaud K, Gaudreau J, Chalaye P, Rainville P, Marchand S (2011) Sex differences in perceived pain are affected by an anxious brain. Pain 152(9):2065–2073. https://doi.org/10.1016/j.pain.2011.05.002

    Article  PubMed  Google Scholar 

  23. Maleki N, Linnman C, Brawn J, Burstein R, Becerra L, Borsook D (2012) Her versus his migraine: multiple sex differences in brain function and structure. Brain: J Neurol 135(Pt 8):2546–2559. https://doi.org/10.1093/brain/aws175

    Article  Google Scholar 

  24. Advisory Task Force on Bisphosphonate-Related Ostenonecrosis of the Jaws AAoO, Maxillofacial S (2007) American Association of Oral and Maxillofacial Surgeons position paper on bisphosphonate-related osteonecrosis of the jaws. J Oral Maxillofac Surg 65(3):369–376. https://doi.org/10.1016/j.joms.2006.11.003

    Article  Google Scholar 

  25. Yarom N, Lazarovici TS, Whitefield S, Weissman T, Wasserzug O, Yahalom R (2018) Rapid onset of osteonecrosis of the jaw in patients switching from bisphosphonates to denosumab. Oral Surg Oral Med Oral Pathol Oral Radiol 125(1):27–30. https://doi.org/10.1016/j.oooo.2017.09.014

    Article  PubMed  Google Scholar 

  26. Bonica JJ (1990) The managment of pain. lea & Febiger, philadelfia

    Google Scholar 

  27. Gracely RH, Lynch SA, Bennett GJ (1992) Painful neuropathy: altered central processing maintained dynamically by peripheral input. Pain 51(2):175–194

    Article  CAS  Google Scholar 

  28. Benoliel S (2015) Orofacial pain and headache. Anatomy and neurophysiology of orofacial pain, 2nd edn. Quintessencen Publishing

  29. 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, 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 Mineral Res 30(1):3–23. https://doi.org/10.1002/jbmr.2405

    Article  Google Scholar 

Download references

Acknowledgements

YZ and ZG made substantial contributions to the study’s conception and design and acquisition of data. YH contributed to the interpretation of data, drafted the submitted article, and provided final approval of the version to be published. SM conducted the statistics. YS, NK, YH, and YZ wrote, revised, and approved the manuscript.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Yaron Haviv.

Ethics declarations

The Institutional Review Board approved the study protocol (0612-14-HMO).

Conflict of interest

The authors declare that they have no conflict of interest.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Haviv, Y., Geller, Z., Mazor, S. et al. Pain characteristics in medication-related osteonecrosis of the jaws. Support Care Cancer 29, 1073–1080 (2021). https://doi.org/10.1007/s00520-020-05600-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00520-020-05600-z

Keywords

Navigation