Quantitation and distribution of metallic elements in sequestra of medication-related osteonecrosis of jaw (MRONJ) using inductively coupled plasma atomic emission spectroscopy and synchrotron radiation X-ray fluorescence analysis
Medication-related osteonecrosis of the jaw (MRONJ) is a serious adverse effect of antiresorptive agents like bisphosphonates. Abnormal concentrations of various trace metallic elements contained in bone minerals have been associated with MRONJ. In this study, we focused on trace metallic elements contained in the MRONJ sequestrum; their content and distribution were compared to those in osteomyelitis and non-inflammatory bones using inductively coupled plasma atomic emission spectroscopy (ICP-AES) and synchrotron radiation X-ray fluorescence analysis (SR-XRF). On ICP-AES analyses, various trace elements (Co, Cr, Cu, Fe, K, Mg, Ni, Sb, Ti, V, Pb) were significantly more in MRONJ sequestra than non-inflammatory bones. The Cu content was significantly higher in MRONJ sequestra than osteomyelitis and non-inflammatory bones. The Cu content in MRONJ sequestra was high even after decalcification. Additionally, Cu was distributed along the trabecular structures in decalcified MRONJ specimens, as observed using SR-XRF analysis. Therefore, this study was indicative of the characteristic behavior of Cu in MRONJ.
KeywordsMedication-related osteonecrosis of the jaw (MRONJ) Trace metallic element Inductively coupled plasma atomic emission spectroscopy (ICP-AES) Synchrotron radiation X-ray fluorescence analysis (SR-XRF)
The authors would like to thank Ms. Miwako Hamagaki for the preparation of the specimens for elemental analyses. SR-XRF measurements were performed with the approval of the Photon Factory Program Advisory Committee (Proposal no. 2016G018). This work was supported by a Grant-in Aid from the Japan Society for the Promotion of Science (JSPS no. 16H02688).
Compliance with ethical standards
Conflict of interest
The authors declare no conflict of interest.
All patients provided informed consent and the study protocol was approved by the Ethical Committee of Tokyo Medical and Dental University (D2016-002)
- 3.Coleman R, Woodward E, Brown J, Cameron D, Bell R, Dodwell D, Keane M, Gil M, Davies C, Burkinshaw R, Houston SJ, Grieve RJ, Barrett-Lee PJ, Thorpe H (2011) Safety of zoledronic acid and incidence of osteonecrosis of the jaw (ONJ) during adjuvant therapy in a randomised phase III trial (AZURE: BIG 01–04) for women with stage II/III breast cancer. Breast Cancer Res Treat 127:429–438CrossRefGoogle Scholar
- 4.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. J Clin Oncol 27:5356–5362CrossRefGoogle Scholar
- 5.Lo JC, O’Ryan FS, Gordon NP, Yang J, Hui RL, Martin D, Hutchinson M, Lathon PV, Sanchez G, Silver P, Chandra M, McCloskey CA, Staffa JA, Willy M, Selby JV, Go AS (2010) Prevalence of osteonecrosis of the jaw in patients with oral bisphosphonate exposure. J Oral Maxillofac Surg 68:243–253CrossRefGoogle Scholar
- 15.Newnham RR (1994) Essentiality of boron for healthy bones and joints. Environ Health Perspect 102:83–85Google Scholar
- 16.Tisato F, Marzano C, Porchia M, Pellei M, Santini C (2010) Copper in diseases and treatments, and copper-based anticancer strategies. Med Res Rev 30:708–749Google Scholar
- 19.Qu X, He Z, Qiao H, Zhai Z, Mao Z, Yu Z, Dai K (2018) Serum copper levels are associated with bone mineral density and total fracture. J Orthop Transl 14:34–44Google Scholar
- 25.World Health Organization (1996) Trace elements in human nutrition and health. World Health Organization, Geneva, pp 123–143. http://www.who.int/nutrition/publications/micronutrients/9241561734/en/. Accessed 15 Oct 2018