To characterise pain from medication-related osteonecrosis of the jaws (MRONJ) and the effects of antimicrobial treatment on it.
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.
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).
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 to check access.
Buy single article
Instant access to the full article PDF.
Price includes VAT for USA
Subscribe to journal
Immediate online access to all issues from 2019. Subscription will auto renew annually.
This is the net price. Taxes to be calculated in checkout.
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
Raffa RBLR, Pergolizzi JV, Porreca F, Tallarida RJ (2012b) Chemotherapy-induced neuropathic pain. Orofacial neuropathy and pain in cancer patients. CRC Press
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
Sharav YBR (2015) Orofacial pain and headache. Acute orofacial pain, 2nd edn. Quintessence Publishing Co, USA
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
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
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
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
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
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
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
Bonica JJ (1990) The managment of pain. lea & Febiger, philadelfia
Gracely RH, Lynch SA, Bennett GJ (1992) Painful neuropathy: altered central processing maintained dynamically by peripheral input. Pain 51(2):175–194
Benoliel S (2015) Orofacial pain and headache. Anatomy and neurophysiology of orofacial pain, 2nd edn. Quintessencen Publishing
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
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.
The Institutional Review Board approved the study protocol (0612-14-HMO).
Conflict of interest
The authors declare that they have no conflict of interest.
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
About this article
Cite this article
Haviv, Y., Geller, Z., Mazor, S. et al. Pain characteristics in medication-related osteonecrosis of the jaws. Support Care Cancer (2020). https://doi.org/10.1007/s00520-020-05600-z
- Oral oncology
- Osteonecrosis of the jaws