Exploring the therapeutic synergy of drug-lifestyle interventions in fluorosis: a randomized trial on cardiovascular metabolic outcomes from the China fluorosis cohort (CFC)

Introduction: Skeletal fluorosis patients face a markedly elevated risk of cardiovascular metabolic abnormalities, including endothelial dysfunction, excessive oxidative stress, and impaired calcium-phosphate metabolism. Current clinical interventions for this condition are limited to symptomatic analgesia and conventional anti-osteoporotic treatments, and lack targeted therapeutic strategies for the "kidney deficiency and blood stasis" pathogenesis of skeletal fluorosis that can synergistically protect both the skeletal and cardiovascular systems. Methods: (Drug 3)-in conjunction with lifestyle modifications on cardiovascular metabolic outcomes. Results: < 0.05). Additionally, the interaction models outperformed the main-effect models, confirming the dynamic synergistic effect between lifestyle interventions and TCM pharmacotherapy. Discussion: These findings highlight the clinical necessity of integrating behavioral interventions with pharmacotherapy to optimize cardiovascular metabolic safety in the clinical management of skeletal fluorosis. Based on these results, we propose a novel theoretical framework-Personalized Behavioral-Integrated Therapy (PBIT)-which guides the incorporation of patient-specific behavioral and demographic factors into tailored treatment strategies, thereby improving the precision and clinical outcomes of skeletal fluorosis treatment.