{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T23:35:21Z","timestamp":1793144121727,"version":"4.5.0"},"reference-count":119,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2022,7,31]],"date-time":"2022-07-31T00:00:00Z","timestamp":1659225600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Renal osteodystrophy is common in patients with chronic kidney disease and end-stage renal disease and leads to the risks of fracture and extraosseous vascular calcification. Secondary hyperparathyroidism (SHPT) is characterized by a compensatory increase in parathyroid hormone (PTH) secretion in response to decreased renal phosphate excretion, resulting in potentiating bone resorption and decreased bone quantity and quality. Calcium-sensing receptors (CaSRs) are group C G-proteins and negatively regulate the parathyroid glands through (1) increasing CaSR insertion within the plasma membrane, (2) increasing 1,25-dihydroxy vitamin D3 within the kidney and parathyroid glands, (3) inhibiting fibroblast growth factor 23 (FGF23) in osteocytes, and (4) attenuating intestinal calcium absorption through Transient Receptor Potential Vanilloid subfamily member 6 (TRPV6). Calcimimetics (CaMs) decrease PTH concentrations without elevating the serum calcium levels or extraosseous calcification through direct interaction with cell membrane CaSRs. CaMs reduce osteoclast activity by reducing stress-induced oxidative autophagy and improving Wnt-10b release, which promotes the growth of osteoblasts and subsequent mineralization. CaMs also directly promote osteoblast proliferation and survival. Consequently, bone quality may improve due to decreased bone resorption and improved bone formation. CaMs modulate cardiovascular fibrosis, calcification, and renal fibrosis through different mechanisms. Therefore, CaMs assist in treating SHPT. This narrative review focuses on the role of CaMs in renal osteodystrophy, including their mechanisms and clinical efficacy.<\/jats:p>","DOI":"10.3390\/ph15080952","type":"journal-article","created":{"date-parts":[[2022,8,1]],"date-time":"2022-08-01T04:04:00Z","timestamp":1659326640000},"page":"952","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Role of Calcimimetics in Treating Bone and Mineral Disorders Related to Chronic Kidney Disease"],"prefix":"10.3390","volume":"15","author":[{"given":"Yi-Chou","family":"Hou","sequence":"first","affiliation":[{"name":"Division of Nephrology, Department of Medicine, Cardinal-Tien Hospital, School of Medicine, Fu-Jen Catholic University, New Taipei City 24205, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0370-3951","authenticated-orcid":false,"given":"Cai-Mei","family":"Zheng","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Internal Medicine, Shuang Ho Hospital, School of Medicine, College of Medicine, Taipei Medical University, New Taipei City 11031, Taiwan"},{"name":"TMU Research Centre of Urology and Kidney, Taipei Medical University, New Taipei City 11031, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5027-390X","authenticated-orcid":false,"given":"Hui-Wen","family":"Chiu","sequence":"additional","affiliation":[{"name":"TMU Research Centre of Urology and Kidney, Taipei Medical University, New Taipei City 11031, Taiwan"},{"name":"Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, New Taipei City 11031, Taiwan"},{"name":"Department of Medical Research, Shuang Ho Hospital, Taipei Medical University, New Taipei City 11031, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen-Chih","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Biology and Anatomy, National Defense Medical Center, Taipei 11490, Taiwan"},{"name":"Section of Nephrology, Department of Medicine, Antai Medical Care Corporation, Anti Tian-Sheng Memorial Hospital, Pingtung 92842, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7062-8560","authenticated-orcid":false,"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, Buddhist Tzu Chi University, Hualien 97004, Taiwan"},{"name":"Division of Nephrology, Department of Medicine, Fu-Jen Catholic University Hospital, School of Medicine, Fu-Jen Catholic University, New Taipei City 24205, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9452-5179","authenticated-orcid":false,"given":"Chien-Lin","family":"Lu","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Medicine, Fu-Jen Catholic University Hospital, School of Medicine, Fu-Jen Catholic University, New Taipei City 24205, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,7,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Kidney Disease: Improving Global Outcomes (KDIGO) CKD-MBD Update Work Group (2017). KDIGO 2017 Clinical Practice Guideline Update for the Diagnosis, Evaluation, Prevention, and Treatment of Chronic Kidney Disease-Mineral and Bone Disorder (CKD-MBD). Kidney Int. Suppl. 2011, 7, 1\u201359.","DOI":"10.1016\/j.kisu.2017.04.001"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"715","DOI":"10.1038\/ki.2009.551","article-title":"Vitamin D deficiency and anemia in early chronic kidney disease","volume":"77","author":"Patel","year":"2010","journal-title":"Kidney Int."},{"key":"ref_3","first-page":"i2","article-title":"The Pathophysiology of Secondary Hyperparathyroidism and the Consequences of Uncontrolled Mineral Metabolism in Chronic Kidney Disease: The Role of COSMOS","volume":"1","author":"Carrera","year":"2008","journal-title":"NDT Plus"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1111\/nep.13457","article-title":"Mineral bone disorders in chronic kidney disease","volume":"23","author":"Hou","year":"2018","journal-title":"Nephrology"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"e277","DOI":"10.1016\/j.ddtec.2012.11.002","article-title":"Allosteric modulators of the extracellular calcium receptor","volume":"10","author":"Nemeth","year":"2013","journal-title":"Drug Discov. Today. Technol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1305","DOI":"10.1681\/ASN.2005111185","article-title":"Fibroblast growth factor 23 is a counter-regulatory phosphaturic hormone for vitamin D","volume":"17","author":"Liu","year":"2006","journal-title":"J. Am. Soc. Nephrol. JASN"},{"key":"ref_7","first-page":"R78","article-title":"Phosphaturic effect of parathyroid hormone in the spontaneously hypertensive rat","volume":"267","author":"Berndt","year":"1994","journal-title":"Am. J. Physiol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"611","DOI":"10.1038\/nrendo.2009.196","article-title":"The FGF23-Klotho axis: Endocrine regulation of phosphate homeostasis","volume":"5","author":"Razzaque","year":"2009","journal-title":"Nat. Rev. Endocrinol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1038\/s41574-018-0115-0","article-title":"The calcium-sensing receptor in physiology and in calcitropic and noncalcitropic diseases","volume":"15","author":"Hannan","year":"2018","journal-title":"Nat. Rev. Endocrinol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1038\/nrm3254","article-title":"Building strong bones: Molecular regulation of the osteoblast lineage","volume":"13","author":"Long","year":"2011","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1659","DOI":"10.2106\/JBJS.M.01096","article-title":"A review of osteocyte function and the emerging importance of sclerostin","volume":"96","author":"Compton","year":"2014","journal-title":"J. Bone Jt. Surg. Am. Vol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1196\/annals.1365.035","article-title":"Bone remodeling","volume":"1092","author":"Hadjidakis","year":"2006","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1359\/JBMR.0301226","article-title":"PTH differentially regulates expression of RANKL and OPG","volume":"19","author":"Huang","year":"2004","journal-title":"J. Bone Miner. Res. Off. J. Am. Soc. Bone Miner. Res."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1016\/j.coph.2015.03.005","article-title":"Parathyroid hormone: Anabolic and catabolic actions on the skeleton","volume":"22","author":"Silva","year":"2015","journal-title":"Curr. Opin. Pharmacol."},{"key":"ref_15","unstructured":"Glorieux, F.H., Pettifor, J.M., and J\u00dcPpner, H. (2003). CHAPTER 15\u2014Bone Histomorphometry. Pediatric Bone, Academic Press."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"S151","DOI":"10.2215\/CJN.04301206","article-title":"Histomorphometric measurements of bone turnover, mineralization, and volume","volume":"3","author":"Ott","year":"2008","journal-title":"Clin. J. Am. Soc. Nephrol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1038\/ki.2015.156","article-title":"Sclerostin and DKK1: New players in renal bone and vascular disease","volume":"88","author":"Evenepoel","year":"2015","journal-title":"Kidney Int."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1016\/j.bone.2016.03.017","article-title":"Bone loss in chronic kidney disease: Quantity or quality?","volume":"87","author":"Zheng","year":"2016","journal-title":"Bone"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"813","DOI":"10.1093\/oxfordjournals.ndt.a027404","article-title":"Renal bone disease in 76 patients with varying degrees of predialysis chronic renal failure: A cross-sectional study","volume":"11","author":"Coen","year":"1996","journal-title":"Nephrol. Dial. Transplant."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"289","DOI":"10.5935\/0101-2800.20140042","article-title":"Association between indoxyl sulfate and bone histomorphometry in pre-dialysis chronic kidney disease patients","volume":"36","author":"Barreto","year":"2014","journal-title":"J. Bras. Nefrol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"738","DOI":"10.1038\/sj.ki.5002097","article-title":"Indoxyl sulfate induces skeletal resistance to parathyroid hormone in cultured osteoblastic cells","volume":"71","author":"Iwasaki","year":"2007","journal-title":"Kidney Int."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"2176","DOI":"10.1093\/ndt\/gfr647","article-title":"Indoxyl sulphate inhibits osteoclast differentiation and function","volume":"27","author":"Mozar","year":"2012","journal-title":"Nephrol. Dial. Transplant."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Liu, W.-C., Shyu, J.-F., Lim, P.S., Fang, T.-C., Lu, C.-L., Zheng, C.-M., Hou, Y.-C., Wu, C.-C., Lin, Y.-F., and Lu, K.-C. (2020). Concentration and Duration of Indoxyl Sulfate Exposure Affects Osteoclastogenesis by Regulating NFATc1 via Aryl Hydrocarbon Receptor. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21103486"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1016\/j.gene.2005.07.016","article-title":"The insulin-like growth factor-I gene and osteoporosis: A critical appraisal","volume":"361","author":"Niu","year":"2005","journal-title":"Gene"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"E3","DOI":"10.1152\/ajpendo.00157.2010","article-title":"The many facets of PPARgamma: Novel insights for the skeleton","volume":"299","author":"Kawai","year":"2010","journal-title":"Am. J. Physiol. Endocrinol. Metab."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1016\/j.kint.2015.12.004","article-title":"Changing bone patterns with progression of chronic kidney disease","volume":"89","author":"Massy","year":"2016","journal-title":"Kidney Int."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1091","DOI":"10.1681\/ASN.2015040339","article-title":"Phosphorylation of Ribosomal Protein S6 Mediates Mammalian Target of Rapamycin Complex 1-Induced Parathyroid Cell Proliferation in Secondary Hyperparathyroidism","volume":"27","author":"Volovelsky","year":"2016","journal-title":"J. Am. Soc. Nephrol. JASN"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1461","DOI":"10.1016\/j.kint.2020.06.034","article-title":"A molecular circadian clock operates in the parathyroid gland and is disturbed in chronic kidney disease associated bone and mineral disorder","volume":"98","author":"Egstrand","year":"2020","journal-title":"Kidney Int."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"310","DOI":"10.1681\/ASN.2007040406","article-title":"EGFR activation increases parathyroid hyperplasia and calcitriol resistance in kidney disease","volume":"19","author":"Arcidiacono","year":"2008","journal-title":"J. Am. Soc. Nephrol. JASN"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"855","DOI":"10.1046\/j.1523-1755.2001.059003855.x","article-title":"p21(WAF1) and transforming growth factor-alpha mediate dietary phosphate regulation of parathyroid cell growth","volume":"59","author":"Dusso","year":"2001","journal-title":"Kidney Int."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1904","DOI":"10.1093\/ndt\/gfh876","article-title":"Downregulation of parathyroid hormone receptor gene expression and osteoblastic dysfunction associated with skeletal resistance to parathyroid hormone in a rat model of renal failure with low turnover bone","volume":"20","author":"Yamato","year":"2005","journal-title":"Nephrol. Dial. Transplant."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1093\/ndt\/17.suppl_10.6","article-title":"Use and indication of vitamin D and vitamin D analogues in patients with renal bone disease","volume":"17","author":"Malluche","year":"2002","journal-title":"Nephrol. Dial. Transplant."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1345","DOI":"10.1038\/ki.2008.60","article-title":"Adynamic bone in patients with chronic kidney disease","volume":"73","author":"Andress","year":"2008","journal-title":"Kidney Int."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"546","DOI":"10.1016\/j.kint.2021.04.043","article-title":"Differentiating the causes of adynamic bone in advanced chronic kidney disease informs osteoporosis treatment","volume":"100","author":"Haarhaus","year":"2021","journal-title":"Kidney Int."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"671","DOI":"10.1038\/nrneph.2013.198","article-title":"Evaluating bone quality in patients with chronic kidney disease","volume":"9","author":"Malluche","year":"2013","journal-title":"Nat. Rev. Nephrol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1111\/j.1476-5381.2011.01511.x","article-title":"New concepts in calcium-sensing receptor pharmacology and signalling","volume":"165","author":"Ward","year":"2012","journal-title":"Br. J. Pharmacol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1152\/physrev.2001.81.1.239","article-title":"Extracellular calcium sensing and extracellular calcium signaling","volume":"81","author":"Brown","year":"2001","journal-title":"Physiol. Rev."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"14177","DOI":"10.1074\/jbc.M408587200","article-title":"Calcium-sensing receptor gene transcription is up-regulated by the proinflammatory cytokine, interleukin-1beta. Role of the NF-kappaB PATHWAY and kappaB elements","volume":"280","author":"Canaff","year":"2005","journal-title":"J. Biol. Chem."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1002\/humu.20827","article-title":"Glial cells missing-2 (GCM2) transactivates the calcium-sensing receptor gene: Effect of a dominant-negative GCM2 mutant associated with autosomal dominant hypoparathyroidism","volume":"30","author":"Canaff","year":"2009","journal-title":"Hum. Mutat."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"394","DOI":"10.3389\/fphys.2016.00394","article-title":"Calcium-Sensing Receptor Gene: Regulation of Expression","volume":"7","author":"Hendy","year":"2016","journal-title":"Front. Physiol."},{"key":"ref_41","first-page":"F454","article-title":"Rat calcium-sensing receptor is regulated by vitamin D but not by calcium","volume":"270","author":"Brown","year":"1996","journal-title":"Am. J. Physiol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1016\/j.mce.2011.05.038","article-title":"Vitamin D and intestinal calcium absorption","volume":"347","author":"Christakos","year":"2011","journal-title":"Mol. Cell. Endocrinol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1053\/jarr.2002.34846","article-title":"Pathogenesis of parathyroid dysfunction in end-stage renal disease","volume":"9","author":"Silver","year":"2002","journal-title":"Adv. Ren. Replace. Ther."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1786","DOI":"10.1172\/JCI118224","article-title":"Parathyroid cell proliferation in normal and chronic renal failure rats. The effects of calcium, phosphate, and vitamin D","volume":"96","author":"Rahamimov","year":"1995","journal-title":"J. Clin. Investig."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1177\/0300060513476600","article-title":"Calcium-sensing receptor and apoptosis in parathyroid hyperplasia of patients with secondary hyperparathyroidism","volume":"41","author":"Lee","year":"2013","journal-title":"J. Int. Med. Res."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"627","DOI":"10.1124\/jpet.103.057273","article-title":"Pharmacodynamics of the type II calcimimetic compound cinacalcet HCl","volume":"308","author":"Nemeth","year":"2004","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1001\/jama.2016.19456","article-title":"Effect of Etelcalcetide vs Placebo on Serum Parathyroid Hormone in Patients Receiving Hemodialysis With Secondary Hyperparathyroidism: Two Randomized Clinical Trials","volume":"317","author":"Block","year":"2017","journal-title":"JAMA"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"e001363","DOI":"10.1161\/JAHA.114.001363","article-title":"Effects of cinacalcet on atherosclerotic and nonatherosclerotic cardiovascular events in patients receiving hemodialysis: The EValuation Of Cinacalcet HCl Therapy to Lower CardioVascular Events (EVOLVE) trial","volume":"3","author":"Wheeler","year":"2014","journal-title":"J. Am. Heart Assoc."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1007\/s40620-019-00677-0","article-title":"New scenarios in secondary hyperparathyroidism: Etelcalcetide. Position paper of working group on CKD-MBD of the Italian Society of Nephrology","volume":"33","author":"Bellasi","year":"2020","journal-title":"J. Nephrol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1049","DOI":"10.1016\/j.tibs.2020.07.008","article-title":"Structural and Biophysical Mechanisms of Class C G Protein-Coupled Receptor Function","volume":"45","author":"Ellaithy","year":"2020","journal-title":"Trends Biochem. Sci."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1159\/000495138","article-title":"Active Vitamin D in Chronic Kidney Disease: Getting Right Back Where We Started from?","volume":"5","author":"Negrea","year":"2019","journal-title":"Kidney Dis."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"v59","DOI":"10.1093\/ndt\/gfh1058","article-title":"Vascular calcification in patients with end-stage renal disease","volume":"19","author":"Floege","year":"2004","journal-title":"Nephrol. Dial. Transplant."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1589","DOI":"10.2147\/DDDT.S134103","article-title":"Role of etelcalcetide in the management of secondary hyperparathyroidism in hemodialysis patients: A review on current data and place in therapy","volume":"12","author":"Friedl","year":"2018","journal-title":"Drug Des. Dev. Ther."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"2237","DOI":"10.1016\/S0140-6736(05)66782-7","article-title":"Calcimimetics and calcilytics--fooling the calcium receptor","volume":"365","author":"Steddon","year":"2005","journal-title":"Lancet"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"4693","DOI":"10.1038\/s41467-019-12399-9","article-title":"Phosphate acts directly on the calcium-sensing receptor to stimulate parathyroid hormone secretion","volume":"10","author":"Centeno","year":"2019","journal-title":"Nat. Commun."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"419","DOI":"10.1159\/000188015","article-title":"Rapid correction of metabolic acidosis in chronic renal failure: Effect on parathyroid hormone activity","volume":"67","author":"Lu","year":"1994","journal-title":"Nephron"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"2163","DOI":"10.1681\/ASN.2014070653","article-title":"Pathophysiologic Changes in Extracellular pH Modulate Parathyroid Calcium-Sensing Receptor Activity and Secretion <em>via<\/em> a Histidine-Independent Mechanism","volume":"26","author":"Campion","year":"2015","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1482","DOI":"10.1210\/me.2011-1370","article-title":"Minireview: The intimate link between calcium sensing receptor trafficking and signaling: Implications for disorders of calcium homeostasis","volume":"26","author":"Breitwieser","year":"2012","journal-title":"Mol. Endocrinol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"e128013","DOI":"10.1172\/jci.insight.128013","article-title":"Activation of the calcium sensing receptor attenuates TRPV6-dependent intestinal calcium absorption","volume":"5","author":"Lee","year":"2019","journal-title":"JCI Insight"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1046\/j.1523-1755.2000.00837.x","article-title":"Calcimimetic NPS R-568 prevents parathyroid hyperplasia in rats with severe secondary hyperparathyroidism","volume":"57","author":"Wada","year":"2000","journal-title":"Kidney Int."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1186\/s12882-020-01880-z","article-title":"Severe chronic kidney disease environment reduced calcium-sensing receptor expression in parathyroid glands of adenine-induced rats even without high phosphorus diet","volume":"21","author":"Uchiyama","year":"2020","journal-title":"BMC Nephrol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"1382","DOI":"10.1016\/j.kint.2021.01.026","article-title":"Decreased monocyte calcium sensing receptor expression in patients with chronic kidney disease is associated with impaired monocyte ability to reduce vascular calcification","volume":"99","author":"Mary","year":"2021","journal-title":"Kidney Int."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"560","DOI":"10.1097\/TP.0b013e3182079431","article-title":"The effect of cinacalcet on bone remodeling and renal function in transplant patients with persistent hyperparathyroidism","volume":"91","author":"Schwarz","year":"2011","journal-title":"Transplantation"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1007\/s00774-009-0102-6","article-title":"Bone metabolism after cinacalcet administration in patients with secondary hyperparathyroidism","volume":"28","author":"Yano","year":"2010","journal-title":"J. Bone Miner. Metab."},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"Hung, K.C., and Chang, J.F. (2020). Therapeutic Effect of Calcimimetics on Osteoclast-Osteoblast Crosslink in Chronic Kidney Disease and Mineral Bone Disease. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21228712"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"1064","DOI":"10.1016\/j.kint.2018.12.015","article-title":"Calcimimetics maintain bone turnover in uremic rats despite the concomitant decrease in parathyroid hormone concentration","volume":"95","author":"Pineda","year":"2019","journal-title":"Kidney Int."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"3597","DOI":"10.1073\/pnas.95.7.3597","article-title":"Osteoclast differentiation factor is a ligand for osteoprotegerin\/osteoclastogenesis-inhibitory factor and is identical to TRANCE\/RANKL","volume":"95","author":"Yasuda","year":"1998","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"284","DOI":"10.3892\/ijmm.2015.2423","article-title":"Bovine parathyroid hormone enhances osteoclast bone resorption by modulating V-ATPase through PTH1R","volume":"37","author":"Liu","year":"2016","journal-title":"Int. J. Mol. Med."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1016\/j.abb.2008.01.011","article-title":"Osteoclast receptors and signaling","volume":"473","author":"Teti","year":"2008","journal-title":"Arch. Biochem. Biophys."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"517","DOI":"10.1172\/JCI5481","article-title":"Bone resorption induced by parathyroid hormone is strikingly diminished in collagenase-resistant mutant mice","volume":"103","author":"Zhao","year":"1999","journal-title":"J. Clin. Investig."},{"key":"ref_71","doi-asserted-by":"crossref","unstructured":"Rybchyn, M.S., Brennan-Speranza, T.C., Mor, D., Cheng, Z., Chang, W., Conigrave, A.D., and Mason, R.S. (2021). The mTORC2 Regulator Homer1 Modulates Protein Levels and Sub-Cellular Localization of the CaSR in Osteoblast-Lineage Cells. Int. J. Mol. Sci., 22.","DOI":"10.20944\/preprints202101.0232.v1"},{"key":"ref_72","doi-asserted-by":"crossref","unstructured":"Zheng, C.-M., Hsu, Y.-H., Wu, C.-C., Lu, C.-L., Liu, W.-C., Zheng, J.-Q., Lin, Y.-F., Chiu, H.-W., Chang, T.-J., and Shyu, J.-F. (2019). Osteoclast-Released Wnt-10b Underlies Cinacalcet Related Bone Improvement in Chronic Kidney Disease. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20112800"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"E608","DOI":"10.1152\/ajpendo.00229.2004","article-title":"Involvement of calcium-sensing receptor in osteoblastic differentiation of mouse MC3T3-E1 cells","volume":"288","author":"Yamauchi","year":"2005","journal-title":"Am. J. Physiol. Endocrinol. Metab."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1002\/jbmr.4459","article-title":"Cinacalcet improves bone parameters through regulation of osteoclast endoplasmic reticulum stress, autophagy, and apoptotic pathways in chronic kidney disease-mineral and bone disorder","volume":"37","author":"Chiu","year":"2021","journal-title":"J. Bone Miner. Res."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"68","DOI":"10.4161\/org.4.2.5851","article-title":"Wnt signal transduction pathways","volume":"4","author":"Komiya","year":"2008","journal-title":"Organogenesis"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1186\/s13045-017-0471-6","article-title":"Wnt\/beta-catenin pathway: Modulating anticancer immune response","volume":"10","author":"Pai","year":"2017","journal-title":"J. Hematol. Oncol."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1016\/j.tibs.2009.10.002","article-title":"GSK3: A multifaceted kinase in Wnt signaling","volume":"35","author":"Wu","year":"2010","journal-title":"Trends Biochem. Sci."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"1621","DOI":"10.1359\/jbmr.2002.17.9.1621","article-title":"Mechanical properties of adult vertebral cancellous bone: Correlation with collagen intermolecular cross-links","volume":"17","author":"Banse","year":"2002","journal-title":"J. Bone Miner. Res. Off. J. Am. Soc. Bone Miner. Res."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"547","DOI":"10.1097\/MNH.0000000000000062","article-title":"Advanced glycation end product accumulation: A new enemy to target in chronic kidney disease?","volume":"23","author":"Mallipattu","year":"2014","journal-title":"Curr. Opin. Nephrol. Hypertens."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"521","DOI":"10.1007\/s00223-011-9488-y","article-title":"Nonenzymatic Cross-Linking Pentosidine Increase in Bone Collagen and Are Associated with Disorders of Bone Mineralization in Dialysis Patients","volume":"88","author":"Mitome","year":"2011","journal-title":"Calcif. Tissue Int."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"F1315","DOI":"10.1152\/ajprenal.00552.2009","article-title":"Effect of paricalcitol and cinacalcet on serum phosphate, FGF-23, and bone in rats with chronic kidney disease","volume":"298","author":"Finch","year":"2010","journal-title":"Am. J. Physiol. Ren. Physiol."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"306","DOI":"10.1016\/j.ejphar.2009.05.013","article-title":"The calcimimetic AMG 641 abrogates parathyroid hyperplasia, bone and vascular calcification abnormalities in uremic rats","volume":"616","author":"Henley","year":"2009","journal-title":"Eur. J. Pharmacol."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1007\/s00223-015-0013-6","article-title":"Biphasic Effects of Vitamin D and FGF23 on Human Osteoclast Biology","volume":"97","author":"Allard","year":"2015","journal-title":"Calcif. Tissue Int."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"2265","DOI":"10.1002\/jbmr.4122","article-title":"Inhibition of Osteoclast Differentiation by 1.25-D and the Calcimimetic KP2326 Reveals 1.25-D Resistance in Advanced CKD","volume":"35","author":"Bernardor","year":"2020","journal-title":"J. Bone Miner. Res. Off. J. Am. Soc. Bone Miner. Res."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"1215","DOI":"10.1016\/j.bbrc.2006.07.192","article-title":"Extracellular calcium sensing in rat aortic vascular smooth muscle cells","volume":"348","author":"Smajilovic","year":"2006","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"F946","DOI":"10.1152\/ajprenal.00474.2006","article-title":"Extracellular calcium-sensing receptor is functionally expressed in human artery","volume":"293","author":"Molostvov","year":"2007","journal-title":"Am. J. Physiol.-Ren. Physiol."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"260","DOI":"10.1093\/cvr\/cvn279","article-title":"Calcification is associated with loss of functional calcium-sensing receptor in vascular smooth muscle cells","volume":"81","author":"Alam","year":"2009","journal-title":"Cardiovasc. Res."},{"key":"ref_88","doi-asserted-by":"crossref","unstructured":"Qu, Y.Y., Hui, J., Wang, L.M., Tang, N., Zhong, H., Liu, Y.M., Li, Z., Feng, Q., and He, F. (2016). Reduced Expression of the Extracellular Calcium-Sensing Receptor (CaSR) Is Associated with Activation of the Renin-Angiotensin System (RAS) to Promote Vascular Remodeling in the Pathogenesis of Essential Hypertension. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0157456"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.exger.2017.07.008","article-title":"An animal model of co-existing sarcopenia and osteoporotic fracture in senescence accelerated mouse prone 8 (SAMP8)","volume":"97","author":"Zhang","year":"2017","journal-title":"Exp. Gerontol."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"1163","DOI":"10.3389\/fphar.2018.01163","article-title":"Calcium Sensing Receptor-Related Pathway Contributes to Cardiac Injury and the Mechanism of Astragaloside IV on Cardioprotection","volume":"9","author":"Lu","year":"2018","journal-title":"Front. Pharmacol."},{"key":"ref_91","first-page":"F248","article-title":"Juxtaglomerular cell CaSR stimulation decreases renin release via activation of the PLC\/IP3 pathway and the ryanodine receptor","volume":"304","author":"Reddy","year":"2012","journal-title":"Am. J. Physiol. Ren. Physiol."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1007\/s00223-010-9442-4","article-title":"Effect of calcium and the calcimimetic AMG 641 on matrix-Gla protein in vascular smooth muscle cells","volume":"88","author":"Mendoza","year":"2011","journal-title":"Calcif. Tissue Int."},{"key":"ref_93","doi-asserted-by":"crossref","unstructured":"Hou, Y.-C., Lu, C.-L., Zheng, C.-M., Chen, R.-M., Lin, Y.-F., Liu, W.-C., Yen, T.-H., Chen, R., and Lu, K.-C. (2019). Emerging Role of Vitamins D and K in Modulating Uremic Vascular Calcification: The Aspect of Passive Calcification. Nutrients, 11.","DOI":"10.3390\/nu11010152"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1016\/j.bbrc.2006.01.135","article-title":"Expression of a functional extracellular calcium-sensing receptor in human aortic endothelial cells","volume":"342","author":"Ziegelstein","year":"2006","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"256","DOI":"10.1093\/cvr\/cvt249","article-title":"Calcimimetics increase CaSR expression and reduce mineralization in vascular smooth muscle cells: Mechanisms of action","volume":"101","author":"Boudot","year":"2014","journal-title":"Cardiovasc. Res."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"728","DOI":"10.1016\/j.bbrc.2017.04.126","article-title":"Role of the calcium sensing receptor in cardiomyocyte apoptosis via mitochondrial dynamics in compensatory hypertrophied myocardium of spontaneously hypertensive rat","volume":"487","author":"Hong","year":"2017","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"789","DOI":"10.1177\/1535370219854325","article-title":"Calcimimetic R568 improved cardiac remodeling by classic and novel renin-angiotensin system in spontaneously hypertensive rats","volume":"244","author":"Zhang","year":"2019","journal-title":"Exp. Biol. Med."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"111","DOI":"10.3892\/mmr.2016.5279","article-title":"Suppression of calcium-sensing receptor ameliorates cardiac hypertrophy through inhibition of autophagy","volume":"14","author":"Liu","year":"2016","journal-title":"Mol. Med. Rep."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1038\/ki.2013.137","article-title":"The calcium sensing receptor modulates fluid reabsorption and acid secretion in the proximal tubule","volume":"84","author":"Capasso","year":"2013","journal-title":"Kidney Int."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"3355","DOI":"10.1172\/JCI57407","article-title":"PTH-independent regulation of blood calcium concentration by the calcium-sensing receptor","volume":"122","author":"Loupy","year":"2012","journal-title":"J. Clin. Investig."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"109","DOI":"10.2217\/17410541.5.2.109","article-title":"CaSR polymorphism Arg990Gly and response to calcimimetic agents in end-stage kidney disease patients with secondary hyperparathyroidism and in cell culture","volume":"5","author":"Rothe","year":"2008","journal-title":"Pers. Med."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"577.6","DOI":"10.1096\/fasebj.2019.33.1_supplement.577.6","article-title":"Calcium-sensing receptor (CaSR) expression and Renin\/Angiotensin System (RAS) in salt-sensitive rats","volume":"33","author":"Okechukwu","year":"2019","journal-title":"FASEB J."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"692","DOI":"10.1016\/S0140-6736(02)09842-2","article-title":"Association between activating mutations of calcium-sensing receptor and Bartter\u2019s syndrome","volume":"360","author":"Watanabe","year":"2002","journal-title":"Lancet"},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"328","DOI":"10.1093\/ndt\/gfm534","article-title":"Cinacalcet (KRN1493) effectively decreases the serum intact PTH level with favorable control of the serum phosphorus and calcium levels in Japanese dialysis patients","volume":"23","author":"Fukagawa","year":"2008","journal-title":"Nephrol. Dial. Transplant."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1210\/jc.2004-0842","article-title":"Cinacalcet Hydrochloride Maintains Long-Term Normocalcemia in Patients with Primary Hyperparathyroidism","volume":"90","author":"Peacock","year":"2005","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"36","DOI":"10.2215\/CJN.03591006","article-title":"The OPTIMA study: Assessing a new cinacalcet (Sensipar\/Mimpara) treatment algorithm for secondary hyperparathyroidism","volume":"3","author":"Messa","year":"2008","journal-title":"Clin. J. Am. Soc. Nephrol."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"1718","DOI":"10.2215\/CJN.01040308","article-title":"Cinacalcet HCl and concurrent low-dose vitamin D improves treatment of secondary hyperparathyroidism in dialysis patients compared with vitamin D alone: The ACHIEVE study results","volume":"3","author":"Fishbane","year":"2008","journal-title":"Clin. J. Am. Soc. Nephrol."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"2168","DOI":"10.1016\/j.ekir.2020.09.010","article-title":"A Prospective, Randomized Clinical Trial of Etelcalcetide in Patients Receiving Hemodialysis With Secondary Hyperparathyroidism (the DUET Trial)","volume":"5","author":"Itano","year":"2020","journal-title":"Kidney Int. Rep."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"230","DOI":"10.1159\/000156717","article-title":"Long-Term Cinacalcet HCl Treatment Improved Bone Metabolism in Japanese Hemodialysis Patients with Secondary Hyperparathyroidism","volume":"29","author":"Shigematsu","year":"2009","journal-title":"Am. J. Nephrol."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1007\/s10157-012-0665-8","article-title":"Effects of cinacalcet on bone mineral density and bone markers in hemodialysis patients with secondary hyperparathyroidism","volume":"17","author":"Tsuruta","year":"2013","journal-title":"Clin. Exp. Nephrol."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"2482","DOI":"10.1056\/NEJMoa1205624","article-title":"Effect of Cinacalcet on Cardiovascular Disease in Patients Undergoing Dialysis","volume":"367","author":"Chertow","year":"2012","journal-title":"N. Engl. J. Med."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"1128","DOI":"10.2215\/CJN.11141016","article-title":"Calcium-Sensing Receptor Genotype and Response to Cinacalcet in Patients Undergoing Hemodialysis","volume":"12","author":"Moe","year":"2017","journal-title":"Clin. J. Am. Soc. Nephrol. CJASN"},{"key":"ref_113","doi-asserted-by":"crossref","unstructured":"Grzegorzewska, A.E., Frycz, B.A., \u015awiderska, M., Niepolski, L., Mostowska, A., and Jagodzi\u0144ski, P.P. (2019). Calcium-sensing receptor gene (CASR) polymorphisms and CASR transcript level concerning dyslipidemia in hemodialysis patients: A cross-sectional study. BMC Nephrol., 20.","DOI":"10.1186\/s12882-019-1619-0"},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1186\/s12882-018-0910-9","article-title":"Longitudinal changes in bone and mineral metabolism after cessation of cinacalcet in dialysis patients with secondary hyperparathyroidism","volume":"19","author":"Ruderman","year":"2018","journal-title":"BMC Nephrol."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"952","DOI":"10.2215\/CJN.10390917","article-title":"Parathyroidectomy in the Management of Secondary Hyperparathyroidism","volume":"13","author":"Lau","year":"2018","journal-title":"Clin. J. Am. Soc. Nephrol."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"981","DOI":"10.1097\/SLA.0b013e31824c5252","article-title":"Calcimimetics versus parathyroidectomy for treatment of primary hyperparathyroidism: Retrospective chart analysis of a prospective database","volume":"255","author":"Keutgen","year":"2012","journal-title":"Ann. Surg."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"2487","DOI":"10.1681\/ASN.2015060622","article-title":"A Randomized Study Comparing Parathyroidectomy with Cinacalcet for Treating Hypercalcemia in Kidney Allograft Recipients with Hyperparathyroidism","volume":"27","author":"Cruzado","year":"2016","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"2190","DOI":"10.1681\/ASN.2004080657","article-title":"Calcium-Sensing Receptor Expression and Parathyroid Hormone Secretion in Hyperplastic Parathyroid Glands from Humans","volume":"16","author":"Canalejo","year":"2005","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1111\/1744-9987.12058","article-title":"Clinical practice guideline for the management of chronic kidney disease-mineral and bone disorder","volume":"17","author":"Fukagawa","year":"2013","journal-title":"Ther. Apher. Dial."}],"container-title":["Pharmaceuticals"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1424-8247\/15\/8\/952\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T00:00:12Z","timestamp":1760140812000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1424-8247\/15\/8\/952"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,7,31]]},"references-count":119,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2022,8]]}},"alternative-id":["ph15080952"],"URL":"https:\/\/doi.org\/10.3390\/ph15080952","relation":{},"ISSN":["1424-8247"],"issn-type":[{"value":"1424-8247","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,7,31]]}}}