Ibandronate Use in Osteoporotic Vertebral Fractures: A Retrospective Clinical Study Integrated with Exploratory Network Pharmacology and Cross-Cohort Transcriptomic Analysis

Background: Ibandronate is a nitrogen-containing bisphosphonate used in osteoporosis; however, its relationship with vertebral-fracture-related outcomes, pain trajectories, and broader inflammatory–skeletal signaling remains incompletely characterized. Methods: This retrospective observational study included patients with osteoporosis categorized according to ibandronate exposure. The primary outcome was new vertebral fracture occurrence, and the secondary outcome was change in pain severity assessed using the Visual Analog Scale (VAS). Multivariable regression, sensitivity analyses, and exploratory network-pharmacology, transcriptomic, and molecular docking analyses were performed. Results: Forty patients (20 ibandronate, 20 control) were included. Ibandronate use was associated with numerically lower vertebral fracture occurrence, although this did not reach statistical significance in crude or adjusted analyses. Greater pain reduction was observed in unadjusted analyses but was attenuated after multivariable adjustment, and baseline heterogeneity should be considered when interpreting between-group differences. Radiological outcomes did not differ significantly between groups. Exploratory systems-level analyses identified enrichment patterns involving inflammatory signaling, osteoclast differentiation, cytokine-associated pathways, and skeletal regulatory processes; however, these findings should be interpreted as hypothesis-generating and not as evidence of causal biological mechanisms. Conclusions: In this exploratory, hypothesis-generating study, ibandronate use was associated with trends toward lower vertebral fracture occurrence and greater unadjusted pain improvement, although these findings were attenuated after adjustment. The combined clinical, transcriptomic, and computational observations are compatible with the possibility that inflammatory and skeletal regulatory pathways may intersect within a broader systems-level framework relevant to vertebral-fracture-related outcomes in osteoporosis. However, these findings should not be interpreted as direct mechanistic evidence of ibandronate-specific molecular activity or clinical efficacy. Larger prospective studies integrating clinical, radiological, and mechanistic approaches are required to clarify the biological and clinical relevance of these observations.