| アブストラクト | OBJECTIVE: To distinguish jaw misclassification and litigation-related reporting from non-jaw osteonecrosis signals and define their reproducible spectrum. METHODS: We analyzed 20,690,895 deduplicated Food and Drug Administration Adverse Event Reporting System (FAERS) reports (2004Q1-2026Q2), using report-level adjudication and four disproportionality criteria. A descriptive jaw-propensity index (JPI) measured the share of each drug's osteonecrosis reports coded as "jaw." Reporter restrictions and comparisons with Canada Vigilance and the Japanese Adverse Drug Event Report (JADER) database examined reporting bias. These external databases recorded less solicitation. Additional analyses included glucocorticoid stratification, empirical null calibration with unmasking, indication restriction of every surviving non-glucocorticoid drug, time-to-onset modeling, and machine learning. Estimates are reported with 95% confidence intervals. RESULTS: Of 47 signals, 27 passed jaw exclusion (JPI < 0.50) and reporter restriction; the final core was unchanged across thresholds of 0.30-0.70. Tenofovir disoproxil's reporting odds ratio (ROR) fell from 157.9 (153.4-162.6) to 6.33 (5.38-7.45) among health professionals; 84.5% of cases were lawyer-sourced. Canada Vigilance (6.24, 2.00-19.4) and JADER (10.5, 6.60-16.8) were consistent with a litigation-inflated FAERS estimate. Glucocorticoids were replicated in both databases (class RORs 10.3, 54.4). Drug JPI rankings were concordant (r = 0.985, 0.960). All 34 negative controls had ROR < 1 (median 0.16); unmasking rescaled other estimates approximately 2.35-fold. Within-indication analyses detected no residual excess for mycophenolate (0.89) or voxelotor (0.97). Asparaginase combined a within-leukemia residual signal (7.14, 5.10-10.0) with mechanistic evidence and JADER replication (75.7). CONCLUSION: The reproducible spectrum is glucocorticoid-centered, with the asparaginase class the best-supported residual and three drugs unresolved. Jaw misclassification, reporting context, and indication explain much of the apparent spectrum. Spontaneous reports cannot establish causation; these adjudications require cohort confirmation. The JPI and cross-jurisdiction comparisons may inform analyses of other misclassification-prone endpoints. |
|---|
| ジャーナル名 | Frontiers in pharmacology |
|---|
| Pubmed追加日 | 2026/11/5 |
|---|
| 投稿者 | Qi, Lisheng; Qiu, Yu; Wang, Xiaobin; Zhang, Tao; Jiang, Huacai |
|---|
| 組織名 | Department of Spine Surgery, The Affiliated Traditional Chinese Medicine;Hospital, Southwest Medical University, Luzhou, Sichuan, China.;Department of Joint Orthopedics, The First People's Hospital of Yibin, Yibin,;Sichuan, China.;Department of Joint Orthopedics, The Affiliated Traditional Chinese Medicine |
|---|
| Pubmed リンク | https://www.ncbi.nlm.nih.gov/pubmed/42984907/ |
|---|
