Background: Controversy remains regarding the association between antiepileptic drugs and osteopenia, and this study aims to investigate and address this gap using real-world data.Materials and methods: This study included data from the United States (U.S.) Food and Drug Administration Adverse Event Reporting System (FAERS) from the first quarter of 2005 to the first quarter of 2025. A disproportionate analysis method and Bonferroni-corrected p-value were used to detect association signals between antiepileptic drugs and osteopenia. Additionally, subgroup analyses were conducted to explore differences among different age and gender groups.Results: Among the 206,680 adverse events associated with 12 commonly used antiepileptic drugs recorded in the FAERS database during the study period, 181 were attributable to osteopenia. Positive drug safety signals were detected for phenytoin, valproic acid, gabapentin, and eslicarbazepine.Conclusion: Previous studies have only identified a link between phenytoin and osteopenia, while the relationship between valproic acid and this adverse event remains controversial, and gabapentin and eslicarbazepine have not been systematically reported. The findings provide the first evidence of an association between these four antiepileptic drugs and osteopenia, offering insights and guidance for clinical recognition and prevention of such events.

The association between long-term aromatase inhibitor (AI) use and osteoporosis remains controversial. Clarifying this relationship is critical for optimizing the safety of breast cancer survivors. This study collected publicly available data from Q1 2005 through Q1 2025 in the FAERS database. Three types of AIs were included in the study, and adverse events were restricted to the “ Primary Suspect”. The narrow definition of “osteoporosis/osteopenia” in the MedDRA Standard query (SMQ) was used for case screening. Additionally, to investigate adverse outcomes related to osteoporosis, we used vertebral compression fractures-the most typical fracture type in osteoporosis-to explore potential severe outcomes that may occur following drug administration. Disproportionality analysis utilized reporting odds ratio (ROR), PRR, IC, and EBGM. Positive signals were defined only when meeting criteria for all four algorithms. Subgroup and Weibull distribution analyses were performed to assess onset time. A total of 19,590 AIs related adverse event reports were extracted during the monitoring period, of which 665 were osteoporosis-related events, and the patients were mainly women aged 65 years and older. At the system-organ class (SOC) level, musculoskeletal system showed a strongest positive signal. At the SMQ level, anastrozole and letrozole showed significant positive signals associated with osteoporosis. In contrast, exemestane did not reach statistical significance. Similarly, positive disproportionality analysis signals for vertebral compression fracture as an adverse event were identified for anastrozole and letrozole, whereas negative signals were observed for exemestane. TTO analysis showed that exemestane-induced osteoporosis events followed an early failure-type curve with the median time to onset of about 245 days. Analysis reveals distinct bone safety profiles. Anastrozole and letrozole demonstrated significant associations with osteoporosis, whereas exemestane did not, suggesting a superior safety profile. These findings offer reference for clinicians regarding individualized drug selection for patients at high skeletal risk.

Intervertebral disc degeneration (IVDD) is increasingly recognized as a systemic collapse of the epigenetic regulatory network, driven by cellular senescence and environmental stressors. The present review provides an overview of the epigenetic regulatory mechanisms governing IVDD, focusing on the dynamic interplay between DNA methylation, histone modifications, N6‑methyladenosine RNA methylation and the non‑coding RNA regulatory triad (microRNAs, long non‑coding RNAs and circular RNAs). The present study evaluates advanced research methodologies (ranging from site‑specific methylation typing and transposase accessible chromatin sequencing to single‑cell multi‑omics and artificial intelligence‑driven predictive modeling) that resolve the spatial and cellular heterogeneities of the degenerating disc niche. Furthermore, the translational constraints of current animal models were critically assessed, advocating for a strategic shift from acute needle‑puncture insults to physiologically relevant aging and genetically engineered progeroid models to better recapitulate human ‘epigenetic drift’. Finally, the therapeutic potential of targeted epigenetic editing via CRISPR/dCas9 systems and the development of stimuli‑responsive nanocarriers for precision delivery are highlighted. By bridging methodological innovation with robust model selection, the present review offers a roadmap for transitioning molecular insights into clinical regenerative therapies for spinal health.

Intervertebral disc degeneration (IVDD) is one of the main causes of spinal diseases and chronic low back pain. Nucleus pulposus (NP) cells are in a hypoxic environment, and their functions may be regulated by the hypoxia-inducible factor (HIF) family. In recent years, ferroptosis has been confirmed to be closely related to IVDD. HIF-2α plays a key role in hypoxic response, but its mechanism of regulating ferroptosis in IVDD remains unclear. This study aims to explore whether HIF-2α promotes ferroptosis of NP cells by activating the IL-6/hepcidin pathway and inhibiting the expression of iron transporter FPN1. Primary nucleus pulposus cells from rats were cultured under normoxic and hypoxic conditions, with RSL3 and TBHP used as ferroptosis inducers. Cell viability was detected by CCK-8 assay. The expressions of HIF-2α, IL-6 and hepcidin were regulated by siRNA and overexpression plasmids. Gene and protein expressions and their interaction were analyzed by RT-qPCR, Western blot, Co-IP and immunofluorescence. A rat tail vertebra needling-induced IVDD model was established, and MRI assessment, histological staining and biochemical index detection were performed. Hypoxia significantly increased the sensitivity of NP cells to RSL3 and TBHP at 6, 12, and 24 h, and upregulated HIF-2α expression at both mRNA and protein levels. HIF-2α overexpression promoted IL-6 transcription and hepcidin expression, while HIF-2α knockdown blocked hypoxia-induced upregulation of IL-6 and hepcidin. Dual-luciferase reporter assay confirmed that HIF-2α directly activated the IL-6 promoter. Co-IP demonstrated direct binding between hepcidin-25 and FPN1. HIF-2α overexpression increased cell death, lipid ROS, Fe²⁺, MDA and 4-HNE levels, and induced mitochondrial shrinkage characteristic of ferroptosis; these effects were reversed by knockdown of IL-6 or hepcidin. In the rat IVDD model, MRI showed that the Sham group had Grade I-II degeneration, while the IVDD group and IVDD+adenovirus vector group exhibited severe degeneration (Grade III-IV). HIF-2α knockdown significantly alleviated degeneration to Grade II-III. HE staining revealed that HIF-2α knockdown reduced NP tissue damage. HIF-2α knockdown also decreased lipid ROS levels, restored FPN1 and GPX4 protein expression, and reduced hepcidin-25, HIF-2α and IL-6 expression in NP tissues. Immunohistochemistry confirmed that HIF-2α knockdown partially restored FPN1 positive expression and reduced HIF-2α, IL-6 and hepcidin signals. HIF-2α in IVDD promotes ferroptosis by activating the IL-6/hepcidin signaling pathway, inhibiting FPN1 expression, and thereby exacerbating intervertebral disc degeneration. Targeting this pathway may offer a new therapeutic strategy for IVDD.

This study aims to compare the incidence of deep vein thrombosis (DVT) after percutaneous endoscopic lumbar interbody fusion (PELIF), identify independent