Metabolomic profiling reveals salivary hypotaurine as a potential early detection marker for medication-related osteonecrosis of the jaw

• Published in: PloS one 2019-08, Vol.14 (8), p.e0220712-e0220712
• Main Authors: Yatsuoka, Wakako, Ueno, Takao, Miyano, Kanako, Uezono, Yasuhito, Enomoto, Ayame, Kaneko, Miku, Ota, Sana, Soga, Tomoyoshi, Sugimoto, Masahiro, Ushijima, Toshikazu
• Format: Article
• Language: English
• Subjects: Age; Aged; Biology and Life Sciences; Biomarkers - analysis; Biomedical materials; Bisphosphonate-Associated Osteonecrosis of the Jaw - diagnosis; Bisphosphonate-Associated Osteonecrosis of the Jaw - metabolism; Bone cancer; Cancer metastasis; Cancer patients; Cancer prevention; Cancer therapies; Capillary electrophoresis; Carnosine; Case-Control Studies; Chemotherapy; Chromatography; Complications; Complications and side effects; Development and progression; Diagnosis; Drug therapy; Drugs; Electrophoresis; Electrophoresis, Capillary; Female; Histamine; Hospitals; Humans; Jaw; Jaw diseases; Male; Mass Spectrometry; Mass spectroscopy; Medicine and Health Sciences; Metabolites; Metabolomics; Metastases; Metastasis; Middle Aged; Oral cancer; Osteonecrosis; Pathogenesis; Physical Sciences; Polyamines; Propionic acid; R&D; Research & development; Research and Analysis Methods; Saliva; Saliva - chemistry; Scientific imaging; Spectroscopy; Taurine - analogs & derivatives; Taurine - analysis
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0220712

Medication-related osteonecrosis of the jaw (MRONJ) is a rare but serious adverse event of bone-modifying agents used to prevent bone complications in cancer patients with bone metastasis. Currently, early treatment is the only way to prevent further progression, as the pathogenesis of MRONJ has not yet been elucidated, and a standard treatment has not been established. The aim of this study was to identify a marker for early detection marker of MRONJ by exploring substances in saliva specific to MRONJ at an early stage. We collected salivary samples from 17 patients with MRONJ and conducted metabolomic analyses using capillary electrophoresis mass spectrometry for non-targeted analysis of hydrophilic metabolites. In the screening cohort, we compared the saliva of patients with stage ≥1 advanced MRONJ (n = 9) with that of controls without MRONJ before chemotherapy (n = 9). The top 5 most elevated salivary metabolites were histamine, 3-(4-hydroxyphenyl)propionate, malonate, carnosine, and hypotaurine. In the validation cohort, we analyzed additional patients with stage ≥1 advanced MRONJ (n = 8) and controls without MRONJ after chemotherapy (n = 9), confirming a significant 2.28-fold elevation in the salivary concentration of hypotaurine. These results revealed elevated salivary hypotaurine concentration as a potential marker for the early detection of MRONJ.