{"doi":"10.3390/ijms262211208","title":"Integrative Epigenomic and Targeted Protein Analysis in MRONJ: Correlating DNA Methylation with Bone Biomarkers","abstract":"Medication-related osteonecrosis of the jaw (MRONJ) is a severe adverse effect of antiresorptive agents, including bisphosphonates (BPs) and denosumab (DMB). We conducted a case–control epigenome-wide association study (EWAS) of 24 cancer patients treated with BPs or BPs + DMB using the Infinium® MethylationEPIC v2.0 to explore epigenetic differences associated with MRONJ. Differentially methylated positions (DMPs) and regions (DMRs) were assessed across three analyses: MRONJ vs. controls (main), BPs-MRONJ vs. BPs-controls, and BPs/DMB-MRONJ vs. BPs/DMB-controls. Eight plasma bone biomarkers were quantified by Luminex and correlated with top methylation sites. We identified 10 DMPs and 4 DMRs at suggestive significance (p < 1 × 10−5). cg1913766 in the NOP56 promoter was hypomethylated in the main analysis (p = 2.19 × 10−7) and in BPs-MRONJ (p = 4.80 × 10−6), correlating with osteocalcin (p = 0.02 and 0.03, respectively). TNXB cg21289669 was hypermethylated in the main analyses (p = 6.31 × 10−6), and TNXB locus formed a DMR (p = 3.30 × 10−10) in the main and BPs-MRONJ analyses (p = 2.76 × 10−7). cg11392877 in PDE8A was hypomethylated in BPs/DMB-MRONJ (p = 5.35 × 10−7). TRIM15 was a significant DMR in BPs-MRONJ and the main analysis (p = 3.30 × 10−10). TRIM15, TNXB, and PDE8A regulate collagen I, while NOP56 supports ribosome biogenesis, potentially contributing to MRONJ. Given the small sample size, these findings are preliminary and validation in larger studies is warranted.","journal":"International Journal of Molecular Sciences","year":2025,"id":581784,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9558,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":733660,"name":"Marwa Tantawy","orcid":"0000-0001-6767-1093","position":1,"is_corresponding":false},{"id":71312,"name":"Daqing Wang","orcid":"0000-0002-7134-3065","position":2,"is_corresponding":false},{"id":1493682,"name":"Elysse Castro-Hall","orcid":null,"position":3,"is_corresponding":false},{"id":513245,"name":"María T. Abreu","orcid":"0000-0002-7294-0574","position":4,"is_corresponding":false},{"id":381816,"name":"Alessandro Villa","orcid":"0000-0002-1966-6000","position":5,"is_corresponding":false},{"id":282177,"name":"Joseph Katz","orcid":"0000-0002-0741-8149","position":6,"is_corresponding":false},{"id":388358,"name":"L. Shannon Holliday","orcid":"0000-0002-0844-1965","position":7,"is_corresponding":false},{"id":388359,"name":"Yan Gong","orcid":"0000-0002-8218-1620","position":8,"is_corresponding":false},{"id":1493352,"name":"Rahaf AlShammari","orcid":"0009-0006-5165-2190","position":0,"is_corresponding":true}],"reference_count":42,"raw_metadata":null,"created_at":"2026-07-19T02:58:51.328454Z","pmid":"41303691","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}