{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T10:37:21Z","timestamp":1786444641950,"version":"build-2736575974"},"reference-count":186,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T00:00:00Z","timestamp":1786406400000},"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. Immunol."],"abstract":"<jats:p>Chronic kidney disease (CKD) disrupts mineral metabolism, skeletal remodeling, vascular homeostasis, and immune regulation, producing the systemic phenotype of CKD-mineral and bone disorder (CKD-MBD) together with chronic inflammation and impaired host defense. Osteoimmunology provides a framework for understanding how bone cells, immune cells, and vascular cells interact through shared mediators such as RANKL, osteoprotegerin, NF-kappaB, NFATc1, inflammatory cytokines, fibroblast growth factor 23 (FGF23), Wnt inhibitors, and phosphate-dependent osteogenic signaling pathways. The calcium-sensing receptor (CaSR) is a class C G protein-coupled receptor that regulates parathyroid hormone (PTH) secretion and can signal through G\u03b1q\/11, G\u03b1i\/o, G\u03b112\/13, and beta-arrestin-dependent pathways. CaSR expression and\/or calcium-sensing responses have been described in bone cells, selected immune-lineage cells, and vascular smooth muscle cells, suggesting that CaSR may participate in bone-immune-vascular communication. Calcimimetics, including cinacalcet, etelcalcetide, and evocalcet, are established CaSR-targeting therapies for secondary hyperparathyroidism in dialysis patients. Their best-validated actions are PTH suppression and improvement of calcium-phosphate biochemical control; clinical and experimental studies also support reductions in FGF23, selected bone-turnover markers, and vascular calcification measures. This review critically evaluates the pharmacology of calcimimetics and their potential osteoimmune relevance in CKD-MBD. We emphasize established clinical effects while distinguishing them from mechanistic hypotheses, including direct NLRP3 inflammasome suppression, Th17\/Treg rebalancing, macrophage M1-to-M2 polarization, osteocyte connexin-43\/DAMP regulation, and hematopoietic niche restoration, which remain insufficiently validated in human CKD. We propose an integrated bone-vascular-immune framework and identify biomarker-guided and precision-medicine strategies for future calcimimetic research.<\/jats:p>","DOI":"10.3389\/fimmu.2026.1912252","type":"journal-article","created":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T10:14:00Z","timestamp":1786443240000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Calcimimetics and CaSR signaling in CKD-MBD: bone\u2013immune\u2013vascular crosstalk and therapeutic potential"],"prefix":"10.3389","volume":"17","author":[{"given":"Cai-Mei","family":"Zheng","sequence":"first","affiliation":[{"name":"Division of Nephrology, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University","place":["Taipei, Taiwan"]},{"name":"Taipei Medical University-Research Center of Urology and Kidney, Taipei Medical University","place":["Taipei, Taiwan"]},{"name":"Division of Nephrology, Department of Internal Medicine, Taipei Medical University Shuang Ho Hospital","place":["New Taipei City, Taiwan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hsuan-Chu","family":"Hsu","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Internal Medicine, Taipei City Hospital","place":["Taipei, Taiwan"]},{"name":"College of Medicine, National Yang Ming Chiao Tung University","place":["Taipei, Taiwan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi-Chou","family":"Hou","sequence":"additional","affiliation":[{"name":"School of medicine, Fu-Jen Catholic University","place":["New Taipei City, Taiwan"]},{"name":"Department of nephrology, Cardinal Tien hospital","place":["New Taipei City, Taiwan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chien-Lin","family":"Lu","sequence":"additional","affiliation":[{"name":"School of medicine, Fu-Jen Catholic University","place":["New Taipei City, Taiwan"]},{"name":"Division of Nephrology, Department of Medicine, Fu-Jen Catholic University Hospital, Fu Jen Catholic University","place":["New Taipei City, Taiwan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing-Quan","family":"Zheng","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Medicine, Fu-Jen Catholic University Hospital, Fu Jen Catholic University","place":["New Taipei City, Taiwan"]},{"name":"Division of Pulmonary Medicine, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University","place":["Taipei, Taiwan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kuo-Cheng","family":"Lu","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Medicine, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, School of Medicine, Tzu Chi University","place":["Hualien, Taiwan"]},{"name":"Division of Nephrology, Department of Medicine, 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