Vitamin D3 deficiency and MRONJ: insights from a Bi-Center Study in Argentina. A preliminary cross-sectional study

Gerardo Gilligan; Nicolás Leonardi; Federico Garola; Eduardo Piemonte; René Panico

doi:10.5327/2525-5711.318

Authors

Gerardo Gilligan Universidad Nacional de Córdoba, Facultad de Odontología, Oral Medicine Department – Córdoba, Argentina. https://orcid.org/0000-0002-5201-1444
Nicolás Leonardi Universidad Católica de Córdoba, Oral Medicine Department, School of Dentistry, Science Health Faculty – Córdoba, Argentina. https://orcid.org/0000-0002-4450-0678
Federico Garola Universidad Nacional de Córdoba, Facultad de Odontología, Oral Medicine Department – Córdoba, Argentina. https://orcid.org/0000-0001-8639-2057
Eduardo Piemonte Universidad Nacional de Córdoba, Facultad de Odontología, Oral Medicine Department – Córdoba, Argentina. https://orcid.org/0000-0001-5955-1139
René Panico Universidad Nacional de Córdoba, Facultad de Odontología, Oral Medicine Department – Córdoba, Argentina.

DOI:

https://doi.org/10.5327/2525-5711.318

Keywords:

Osteonecrosis, Cancer, Osteoporosis, Vitamin D3

Abstract

Objetive: The aim of this study is to describe Vitamin D3 levels in patients diagnosed with MRONJ from two centers in Argentina. Methods: A cross-sectional study was conducted on patients from two Oral Medicine centers in Argentina. Patients diagnosed with Medication-related osteonecrosis of the jaw between 2016 and 2022 were included. Vitamin D3 levels were measured in plasma. The STROBE guidelines for reporting cross-sectional studies were followed. Results: The final sample consisted of 53 individuals. Among them, 60.4% had oncological-based diseases while 39.6% were diagnosed with osteoporosis. Oncological patients with Medication-related osteonecrosis showed lower vitamin D3 levels (23.9 ng/mL) compared to the osteoporosis group (32.9 ng/mL) (p=0.03). Conclusion: These preliminary findings described the levels of vitamin D3 in patients diagnosed with MRONJ, highlighting the relevance of investigating the role of vitamin D3 and its clinical outcomes in these patients. Future research in this area could provide valuable insights for a comprehensive understanding of this role.

References

Marx RE. Pamidronate (Aredia) and zoledronate (Zometa) induced avascular necrosis of the jaws: a growing epidemic. J Oral Maxillofac Surg. 2003;61(9):1115-7. https://doi.org/10.1016/s0278-2391(03)00720-1

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(5):527-34. https://doi.org/10.1016/j.joms.2004.02.004

Ruggiero SL, Dodson TB, Aghaloo T, Carlson ER, Ward BB, 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(5):920-43. https://doi.org/10.1016/j.joms.2022.02.008

Kawahara M, Kuroshima S, Sawase T. Clinical considerations for medication-related osteonecrosis of the jaw: a comprehensive literature review. Int J Implant Dent. 2021;7(1):47. https://doi.org/10.1186/s40729-021-00323-0

Fusco V, Campisi G, Bedogni A. One changing and challenging scenario: the treatment of cancer patients with bone metastases by bisphosphonates and denosumab, the cost–benefit evaluation of different options, and the risk of medication-related osteonecrosis of the jaw (MRONJ). Support Care Cancer. 2022;30(9):7047-51. https://doi.org/10.1007/s00520-022-06982-y

Fusco V, Mauceri R, Campisi G, Bedogni A. RE: American Association of Oral and Maxillofacial Surgeons’ position paper on medication-related osteonecrosis of the jaws-2022 update: quantitative risk assessment and controversial issues. J Oral Maxillofac Surg. 2022;80(12):1871-3. https://doi.org/10.1016/j.joms.2022.07.143

Ruggiero SL, Dodson TB, Fantasia J, Goodday R, Aghaloo T, Mehrotra B, et al. American Association of Oral and Maxillofacial Surgeons position paper on medication-related osteonecrosis of the jaw--2014 update. J Oral Maxillofac Surg. 2014;72(10):1938-56. https://doi.org/10.1016/j.joms.2014.04.031

Lorenzo-Pouso AI, Pérez-Sayáns M, García A, Carballo J. Vitamin D supplementation: hypothetical effect on medication-related osteonecrosis of the jaw. Med Hypotheses. 2018;116:79-83. https://doi.org/10.1016/j.mehy.2018.04.023

Heim N, Warwas FB, Wilms CT, Reich RH, Martini M. Vitamin D (25-OHD) deficiency may increase the prevalence of medication-related osteonecrosis of the jaw. J Craniomaxillofac Surg. 2017;45(12):2068-74. https://doi.org/10.1016/j.jcms.2017.09.015

Dalle Carbonare L, Mottes M, Valenti MT. Medication-related osteonecrosis of the jaw (mronj): are antiresorptive drugs the main culprits or only accomplices? The triggering role of vitamin D deficiency. Nutrients. 2021;13(2):561. https://doi.org/10.3390/nu13020561

Elias PM, Williams ML, Choi EH, Feingold KR. Role of cholesterol sulfate in epidermal structure and function: lessons from X-linked ichthyosis. Biochim Biophys Acta. 2014;1841(3):353-61. https://doi.org/10.1016/j.bbalip.2013.11.009

Puche RC. Sobre la prevalencia de hipovitaminosis D en Argentina. Medicina (Buenos Aires). 2015;75(3):183-6.

De Martinis M, Allegra A, Sirufo MM, Tonacci A, Pioggia G, Raggiunti M, et al. Vitamin D deficiency, osteoporosis and effect on autoimmune diseases and hematopoiesis: a review. Int J Mol Sci. 2021;22(16):8855. https://doi.org/10.3390/ijms22168855

Sluyter JD, Manson JE, Scragg R. Vitamin D and clinical cancer outcomes: a review of meta-analyses. JBMR Plus. 2021;5(1):e10420. https://doi.org/10.1002/jbm4.10420

Dalle Carbonare L, Mottes M, Valenti MT. Medication-related osteonecrosis of the jaw (MRONJ): are antiresorptive drugs the main culprits or only accomplices? The triggering role of vitamin D deficiency. Nutrients. 2021;13(2):561. https://doi.org/10.3390/nu13020561

Heim N, Warwas FB, Wilms CT, Reich RH, Martini M. Vitamin D (25-OHD) deficiency may increase the prevalence of medication-related osteonecrosis of the jaw. J Craniomaxillofac Surg. 2017;45(12):2068-74. https://doi.org/10.1016/j.jcms.2017.09.015

Shirani G, Tonkaboni A, Mazani M, Mirzashahi B, Garcia AG, Kharazifard MJ. MRONJ and VIT D insufficiency. Journal of Craniomaxillofacial Research. 2021;8(1):11-5. https://doi.org/10.18502/jcr.v8i1.7151

Demircan S, Isler SC. Changes in serological bone turnover markers in bisphosphonate induced osteonecrosis of the jaws: a case control study. Niger J Clin Pract. 2020;23(2):154-8. https://doi.org/10.4103/njcp.njcp_374_19

Pilz S, Trummer C, Pandis M, Schwetz V, Aberer F, Grübler M, et al. Vitamin D: current guidelines and future outlook. Anticancer Res. 2018;38(2):1145-51. https://doi.org/10.21873/anticanres.12333

Kazemian E, Pourali A, Sedaghat F, Karimi M, Basirat V, Hezaveh ZS, et al. Effect of supplemental vitamin D3 on bone mineral density: a systematic review and meta-analysis. Nutr Rev. 2023;81(5):511-30. https://doi.org/10.1093/nutrit/nuac068

Soma T, Iwasaki R, Sato Y, Kobayashi T, Ito E, Matsumoto T, et al. Osteonecrosis development by tooth extraction in zoledronate treated mice is inhibited by active vitamin D analogues, anti-inflammatory agents or antibiotics. Sci Rep. 2022;12(1):19. https://doi.org/10.1038/s41598-021-03966-6

Michalak F, Dominiak M, Kiryk J, Popecki P, Kubicki D, Matys J, et al. The influence of vitamin D levels and supplementation on the treatment of patients affected by MRONJ. Appl Sci. 2025;15(2):670. https://doi.org/10.3390/app15020670