{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,31]],"date-time":"2026-03-31T07:06:18Z","timestamp":1774940778260,"version":"3.50.1"},"reference-count":51,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,3,31]],"date-time":"2026-03-31T00:00:00Z","timestamp":1774915200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"\n Introduction<\/jats:title>\n 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 \u201ckidney deficiency and blood stasis\u201d pathogenesis of skeletal fluorosis that can synergistically protect both the skeletal and cardiovascular systems.<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n This multicenter randomized controlled trial was conducted on 1,480 skeletal fluorosis patients from the China Fluorosis Cohort (CFC), to investigate the synergistic therapeutic effects of three traditional Chinese medicine (TCM) combinations\u2014\n Ginkgo biloba<\/jats:italic>\n combined with\n Epimedium<\/jats:italic>\n (Drug 1),\n Xianling Gubao<\/jats:italic>\n combined with\n Eucommia ulmoides<\/jats:italic>\n (Drug 2), and\n Gusongbao<\/jats:italic>\n combined with\n Rosa roxburghii<\/jats:italic>\n (Drug 3)\u2014in conjunction with lifestyle modifications on cardiovascular metabolic outcomes.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Smoking and alcohol consumption were identified as independent risk factors for reduced therapeutic efficacy in skeletal fluorosis patients with comorbid cardiovascular metabolic abnormalities (OR = 2.755, 95% CI: 1.400 \u20135.421). Among the three TCM combinations, Drug 2 and Drug 3 significantly counteracted these adverse risk factors, reducing the risk of treatment failure by 53.9% (OR = 0.461) and 57.0% (OR = 0.430), respectively. Drug 3 exhibited superior efficacy in reducing diastolic blood pressure (\n \u03b2<\/jats:italic>\n = \u22122.263,\n P<\/jats:italic>\n = 0.010), while its systolic blood pressure-lowering effect diminished with increasing age. Drug 2 showed synergistic benefits with improved sleep quality (\n \u03b2<\/jats:italic>\n = 1.596,\n P<\/jats:italic>\n = 0.002) and healthy dietary habits (\n \u03b2<\/jats:italic>\n = \u22121.180,\n P<\/jats:italic>\n = 0.001), which enhanced its antihypertensive effects and led to a significant reduction in low-density lipoprotein cholesterol (LDL-C) levels (\n P<\/jats:italic>\n &lt; 0.05). Additionally, the interaction models outperformed the main-effect models, confirming the dynamic synergistic effect between lifestyle interventions and TCM pharmacotherapy.\n <\/jats:p>\n <\/jats:sec>\n \n Discussion<\/jats:title>\n 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\u2014Personalized Behavioral-Integrated Therapy (PBIT)\u2014which 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.<\/jats:p>\n <\/jats:sec>","DOI":"10.3389\/fphar.2026.1737666","type":"journal-article","created":{"date-parts":[[2026,3,31]],"date-time":"2026-03-31T05:34:13Z","timestamp":1774935253000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Exploring the therapeutic synergy of drug-lifestyle interventions in fluorosis: a randomized trial on cardiovascular metabolic outcomes from the China fluorosis cohort (CFC)"],"prefix":"10.3389","volume":"17","author":[{"given":"Yun","family":"Lu","sequence":"first","affiliation":[{"name":"Key Laboratory of Environmental Pollution Monitoring and Disease Control, Ministry of Education, School of Public Health, Guizhou Medical University","place":["Guiyang, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fuyu","family":"Tao","sequence":"additional","affiliation":[{"name":"Key Laboratory of Environmental Pollution Monitoring and Disease Control, Ministry of Education, School of Public Health, Guizhou Medical University","place":["Guiyang, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shaofeng","family":"Wei","sequence":"additional","affiliation":[{"name":"Key Laboratory of Environmental Pollution Monitoring and Disease Control, Ministry of Education, School of Public Health, Guizhou Medical University","place":["Guiyang, China"]},{"name":"Collaborative Innovation Center for Prevention and Control of Endemic and Ethnic Regional Diseases Co. 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