Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Clinical
  • Published:

Clinical status of established MRONJ in oncology patients continuing bone-modifying agents

British Dental Journal volume 236, pages 683–687 (2024)Cite this article

Abstract

The continuation of bone-modifying agents (BMAs) in patients with established medication-related osteonecrosis of the jaw (MRONJ) is a common concern among dentists and oncologists. There is little evidence supporting or refuting the continued use of BMAs or drug holidays and their impact on established MRONJ. This paper evaluates the outcome of continued BMAs use on the patient's MRONJ status. A retrospective review of 29 oncology patients undergoing active cancer care for either metastatic disease or multiple myeloma was conducted. Data on demographics, oncological status, BMA history and MRONJ status were collected. In total, 90% of patients were judged to have healed or stable MRONJ while continuing BMAs. Most patients (69%) continued the same BMA regime (three- or four-weekly) that they were on before developing MRONJ. The average number of BMAs doses received after an MRONJ diagnosis was 12 (range 1-48). Three patients (10.3%) were found to have MRONJ progression, with two patients developing new sites of necrosis. This real-world dataset suggests that the majority of MRONJ cases remain stable and will not worsen with the continuation of BMAs.

Key points

  • Provides wider information and knowledge on the value of bone-modifying agents in the overall health of patients for the general dental practitioner.

  • Alleviates concern that the impact of the drug does not necessarily worsen a patient's medication-related osteonecrosis of the jaw.

  • Provides continued professional development in the arena of dental oncology for general dental practitioners.

  • Provides reassurance that bone-modifying agents retain a low risk of causing medication-related osteonecrosis of the jaw.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Similar content being viewed by others

References

  1. Henry D H, Costa L, Goldwasser F et al. Randomized, double-blind study of denosumab versus zoledronic acid in the treatment of bone metastases in patients with advanced cancer (excluding breast and prostate cancer) or multiple myeloma. J Clin Oncol 2011; 29: 1125-1132.

  2. Yarom N, Shapiro C L, Peterson D E et al. Medication-Related Osteonecrosis of the Jaw: MASCC/ISOO/ASCO Clinical Practice Guideline. J Clin Oncol 2019; 37: 2270-2290.

  3. UK Chemotherapy Board. Medication-related osteonecrosis of the jaw: guidance for the oncology multidisciplinary team. 2019. Available at https://www.rcplondon.ac.uk/guidelines-policy/medication-related-osteonecrosis-jaw-guidance-oncology-multidisciplinary-team (accessed August 2023).

  4. Ramaglia L, Guida A, Iorio-Siciliano V, Cuozzo A, Blasi A, Sculean A. Stage-specific therapeutic strategies of medication-related osteonecrosis of the jaws: a systematic review and meta-analysis of the drug suspension protocol. Clin Oral Investig 2018; 22: 597-615.

  5. Ottesen C, Schiodt M, Gotfredsen K. Efficacy of a high-dose antiresorptive drug holiday to reduce the risk of medication-related osteonecrosis of the jaw (MRONJ): a systematic review. Heliyon 2020; 27: e03795.

  6. Otsuru M, Soutome S, Omori K et al. Relationship between drug holidays of antiresorptive agents and surgical outcomes in cancer patients with medication-related osteonecrosis of the jaw. Int J Environ Res Public Health 2022; 19: 4624.

  7. Ruggiero S L, Dodson T B, Aghaloo T, Carlson E, Ward B B, Kademani D. American Association of Oral and Maxillofacial Surgeons' Position Paper on Medication-Related Osteonecrosis of the Jaws - 2022 Update. J Oral Maxillofac Surg 2022; 80: 920-943.

  8. Nicolatou-Galitis O, Papadopoulou E, Vardas E et al. Alveolar bone histological necrosis observed before extractions in patients, who received bone-targeting agents. Oral Dis 2020; 26: 955-966.

  9. King R, Tanna N, Patel V. Medication-related osteonecrosis of the jaw unrelated to bisphosphonates and denosumab - a review. Oral Surg Oral Med Oral Pathol Oral Radiol 2019; 127: 289-299.

  10. Zebic L, Patel V. Preventing medication-related osteonecrosis of the jaw. BMJ 2019; DOI: 10.1136/bmj.l1733.

  11. McLeod N M, Patel V, Kusanale A, Rogers S N, Brennan P A. Bisphosphonate osteonecrosis of the jaw: a literature review of UK policies versus international policies on the management of bisphosphonate osteonecrosis of the jaw. Br J Oral Maxillofac Surg 2011; 49: 335-342.

  12. Patel S, Patel N, Sassoon I, Patel V. The use of pentoxifylline, tocopherol and clodronate in the management of osteoradionecrosis of the jaws. Radiother Oncol 2021; 156: 209-216.

  13. Otto S, Tröltzsch M, Jambrovic V et al. Tooth extraction in patients receiving oral or intravenous bisphosphonate administration: a trigger for BRONJ development? J Craniomaxillofac Surg 2015; 43: 847-854.

  14. Ristow O, Rückschloβ T, Moratin J et al. Wound closure and alveoplasty after preventive tooth extractions in patients with antiresorptive intake - a randomized pilot trial. Oral Dis 2021; 27: 532-546.

  15. Bedogni A, Blandamura S, Lokmic Z et al. Bisphosphonate-associated jawbone osteonecrosis: a correlation between imaging techniques and histopathology. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2008; 105: 358-364.

  16. Matharu J, Taylor H, Sproat C, Kwok J, Brown J, Patel V. Diffuse sclerosing osteomyelitis: a case series and literature review. Oral Surg Oral Med Oral Pathol Oral Radiol 2020; 129: 437-446.

  17. Mahendran K, Wali R, Patel V. Sickle cell osteomyelitis: a novel approach and review of the literature. Oral Surg 2021; 14: 365-370.

  18. Cheng H, Wali R, Sproat C, Patel V. Secondary chronic osteomyelitis of the mandible: A resistant disease successfully treated with bisphosphonate therapy. Oral Surg 2021; 14: 259-264.

  19. Ottesen C, Schiodt M, Jensen S S, Kofod T, Gotfredsen K. Tooth extractions in patients with cancer receiving high-dose antiresorptive medication: a randomized clinical feasibility trial of drug holiday versus drug continuation. Oral Surg Oral Med Oral Pathol Oral Radiol 2022; 133: 165-173.

  20. Hamid A, Thomas S, Bell C, Gormley M. Case series of medication-related osteonecrosis of the jaw (MRONJ) patients prescribed a drug holiday. Br J Oral Maxillofac Surg 2023; 61: 227-232.

  21. Coleman R, Hadji P, Body J-J et al. Bone health in cancer: ESMO Clinical Practice Guidelines. Ann Oncol 2020; 31: 1650-1663.

  22. Rosen L S, Gordon D, Tchekmedyian S et al. Zoledronic acid versus placebo in the treatment of skeletal metastases in patients with lung cancer and other solid tumours: a phase III, double-blind, randomized trial - the Zoledronic Acid Lung Cancer and Other Solid Tumours Study Group. J Clin Oncol 2003; 21: 3150-3157.

  23. Gnant M, Pfeiler G, Dubsky P C et al. Adjuvant denosumab in breast cancer (ABCSG-18): a multicentre, randomised, double-blind, placebo-controlled trial. Lancet 2015; 386: 433-443.

  24. Smith M R, McGovern F J, Zietman A L et al. Pamidronate to prevent bone loss during androgen-deprivation therapy for prostate cancer. N Engl J Med 2001; 345: 948-955.

  25. Djulbegovic B, Wheatley K, Ross H et al. Bisphosphonates in multiple myeloma. Cochrane Database Syst Rev 2001; DOI: 10.1002/14651858.CD003188.

  26. Early Breast Cancer Trialists' Collaborative Group. Adjuvant bisphosphonate treatment in early breast cancer: meta-analyses of individual patient data from randomised trials. Lancet 2015; 386: 1353-1361.

  27. Morgan G J, Davies F E, Gregory W M et al. First-line treatment with zoledronic acid as compared with clodronic acid in multiple myeloma (MRC Myeloma IX): a randomised controlled trial. Lancet 2010; 376: 1989-1999.

  28. Costa L, Badia X, Chow E, Lipton A, Wardley A. Impact of skeletal complications on patients' quality of life, mobility, and functional independence. Support Care Cancer 2008; 16: 879-889.

  29. Pockett R D, Castellano D, Mcewan P, Oglesby A, Barber B L, Chung K. The hospital burden of disease associated with bone metastases and skeletal-related events in patients with breast cancer, lung cancer, or prostate cancer in Spain. Eur J Cancer Care (Engl) 2010; 19: 755-760.

  30. Von Moos R, Costa L, Gonzalez-Suarez E, Terpos E, Niepel D, Body J-J. Management of bone health in solid tumours: from bisphosphonates to a monoclonal antibody. Cancer Treat Rev 2019; 76: 57-67.

  31. Coleman R E. Clinical features of metastatic bone disease and risk of skeletal morbidity. Clin Cancer Res 2006; DOI: 10.1158/1078-0432.CCR-06-0931.

  32. Patel V, Wali R, Burns M et al. The presenting dental status of solid tumours with bone metastases requiring bone-targeting agents - part 2: breast cancer. Br Dent J 2022; 232: 95-100.

  33. D'Oronzo S, Coleman R, Brown J, Silvestris F. Metastatic bone disease: pathogenesis and therapeutic options: up-date on bone metastasis management. J Bone Oncol 2019; 15: 100205.

  34. Yang M, Yu X. Management of bone metastasis with intravenous bisphosphonates in breast cancer: a systematic review and meta-analysis of dosing frequency. Support Care Cancer 2020; 28: 2533-2540.

  35. Cummings S R, Ferrari S, Eastell R et al. Vertebral fractures after discontinuation of denosumab: a post hoc analysis of the randomized placebo-controlled FREEDOM trial and its extension. J Bone Miner Res 2018; 33: 190-198.

  36. Stewart A F. Clinical practice. Hypercalcaemia associated with cancer. N Engl J Med 2005; 352: 373-379.

  37. Ralston S H, Gallacher S J, Patel U, Campbell J, Boyle I T. Cancer-associated hypercalcaemia: morbidity and mortality. Clinical experience in 126 treated patients. Ann Intern Med 1990; 112: 499-504.

Download references

Author information

Authors and Affiliations

  1. Specialist Registrar in Oral Surgery, Floor 23, Oral Surgery Department, Guy´s and St Thomas´ Hospital, London, SE1 9RT, UK

    Elizabeth Miles

  2. Speciality Dentist in Oral Surgery, Floor 23, Oral Surgery Department, Guy´s and St Thomas´ Hospital, London, SE1 9RT, UK

    Richa Arya

  3. Consultant in Oral Surgery, Floor 23, Oral Surgery Department, Guy´s and St Thomas´ Hospital, London, SE1 9RT, UK

    Christopher Sproat & Vinod Patel

Authors
  1. Elizabeth Miles
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Richa Arya
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Christopher Sproat
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Vinod Patel
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Conception and design of work - Vinod Patel; data collection - Elizabeth Miles, Richa Arya; data analysis and interpretation - Elizabeth Miles, Richa Arya, Christopher Sproat, Vinod Patel; drafting the manuscript - Elizabeth Miles, Vinod Patel; critical revision of manuscript - Elizabeth Miles, Richa Arya, Christopher Sproat, Vinod Patel; final approval of manuscript - Elizabeth Miles, Richa Arya, Christopher Sproat, Vinod Patel.

Corresponding author

Correspondence to Vinod Patel.

Ethics declarations

The authors declare no conflicts of interest.

Ethical approval and consent was not applicable for this retrospective clinical evaluation of historic practice.

Data availability

Not applicable (clinical outcome reporting and sensitive nature of the data).

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Miles, E., Arya, R., Sproat, C. et al. Clinical status of established MRONJ in oncology patients continuing bone-modifying agents. Br Dent J 236, 683–687 (2024). https://doi.org/10.1038/s41415-024-7340-9

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41415-024-7340-9

Search

Advanced search

Quick links