{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T05:02:25Z","timestamp":1790744545651,"version":"4.1.0"},"reference-count":23,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T00:00:00Z","timestamp":1790726400000},"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. Med."],"abstract":"<jats:p>Certain dialysis patients with secondary hyperparathyroidism (SHPT) show partial insensitivity to calcimimetics. These agents are allosteric activators of the calcium-sensing receptor (CaSR) and enhance their sensitivity to extracellular calcium, thereby inhibiting parathyroid hormone (PTH) secretion and eliciting a decrease in serum calcium levels. We hypothesize that the partial attenuated PTH suppression of calcimimetics may be due to the resulting hypocalcemia or a significant decrease in serum calcium levels within the normal range without adequate calcium supplementation. Effective suppression of PTH by calcimimetics inevitably lowers serum calcium levels, which may be further aggravated by ongoing bone mineralization following PTH suppression. This hypocalcemic state or decreased extracellular ionized calcium, if not adequately corrected, acts as a strong trigger for excessive PTH secretion through reducing CaSR activation and stimulating parathyroid chief cells and causing hypertrophy and hyperplasia of parathyroid glands, and then establishing a counter-regulatory feedback circuit that diminishes the therapeutic effect of calcimimetics. High incidence of hypocalcemia, observed in clinical trials of calcimimetics, also bolsters the validity of this hypothesis. Such adverse outcomes may be partially alleviated by timely and adequate calcium and vitamin D supplementation.<\/jats:p>","DOI":"10.3389\/fmed.2026.1907882","type":"journal-article","created":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T04:52:01Z","timestamp":1790743921000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Partial attenuated PTH suppression of calcimimetics may be due to the resulting hypocalcemia or a significant decrease in serum calcium levels within the normal reference range without adequate calcium supplementation"],"prefix":"10.3389","volume":"13","author":[{"given":"De-ru","family":"Kong","sequence":"first","affiliation":[{"name":"Department of Breast and Thyroid Surgery, The First Affiliated Hospital of Chongqing Medical University","place":["Chongqing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"De-ya","family":"Kong","sequence":"additional","affiliation":[{"name":"Xiangya School of Medicine, Central South University","place":["Changsha, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li-yuan","family":"Mu","sequence":"additional","affiliation":[{"name":"Department of Breast and Thyroid Surgery, The First Affiliated Hospital of Chongqing Medical University","place":["Chongqing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiu-quan","family":"Qu","sequence":"additional","affiliation":[{"name":"Department of Breast and Thyroid Surgery, The First Affiliated Hospital of Chongqing Medical University","place":["Chongqing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xi-rui","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Breast and Thyroid Surgery, The First Affiliated Hospital of Chongqing Medical University","place":["Chongqing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ling-quan","family":"Kong","sequence":"additional","affiliation":[{"name":"Department of Breast and Thyroid Surgery, The First Affiliated Hospital of Chongqing Medical University","place":["Chongqing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,30]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"567","DOI":"10.2147\/DDDT.S437903","article-title":"Pharmacokinetics, pharmacodynamics, and safety of evocalcet (KHK7580), a novel calcimimetic agent: an open-label, single- and multiple-dose, phase I trial in healthy Chinese subjects","volume":"18","author":"He","year":"2024","journal-title":"Drug Des Devel Ther"},{"key":"B2","doi-asserted-by":"publisher","first-page":"1119","DOI":"10.1001\/jama.2011.308","article-title":"Serum levels of phosphorus, parathyroid hormone, and calcium and risks of death and cardiovascular disease in individuals with chronic kidney disease: a systematic review and meta-analysis","volume":"305","author":"Palmer","year":"2011","journal-title":"JAMA"},{"key":"B3","doi-asserted-by":"publisher","first-page":"1635451","DOI":"10.3389\/fendo.2025.1635451","article-title":"Machine learning-based predictive model for hungry bone syndrome following parathyroidectomy in secondary hyperparathyroidism","volume":"16","author":"Chai","year":"2025","journal-title":"Front Endocrinol"},{"key":"B4","doi-asserted-by":"publisher","first-page":"156","DOI":"10.1001\/jama.2016.19468","article-title":"Effect of etelcalcetide vs cinacalcet on serum parathyroid hormone in patients receiving hemodialysis with secondary hyperparathyroidism: a randomized clinical trial","volume":"317","author":"Block","year":"2017","journal-title":"JAMA"},{"key":"B5","doi-asserted-by":"publisher","first-page":"201","DOI":"10.1681\/ASN.2021060825","article-title":"Activation of the calcium receptor by calcimimetic agents is preserved despite modest attenuating effects of hyperphosphatemia","volume":"33","author":"Goodman","year":"2022","journal-title":"J Am Soc Nephrol"},{"key":"B6","doi-asserted-by":"publisher","first-page":"161","DOI":"10.2215\/CJN.01760215","article-title":"Clinical and practical use of calcimimetics in dialysis patients with secondary hyperparathyroidism","volume":"11","author":"Bover","year":"2016","journal-title":"Clin J Am Soc Nephrol"},{"key":"B7","doi-asserted-by":"publisher","first-page":"321","DOI":"10.1053\/j.ajkd.2020.02.439","article-title":"Comparative effectiveness of calcimimetic agents for secondary hyperparathyroidism in adults: a systematic review and network meta-analysis","volume":"76","author":"Palmer","year":"2020","journal-title":"Am J Kidney Dis"},{"key":"B8","doi-asserted-by":"publisher","first-page":"2482","DOI":"10.1056\/NEJMoa1205624","article-title":"Effect of cinacalcet on cardiovascular disease in patients undergoing dialysis","volume":"367","year":"2012","journal-title":"N Engl J Med"},{"key":"B9","doi-asserted-by":"publisher","first-page":"254","DOI":"10.1016\/j.ekir.2020.11.023","article-title":"Surgical management of secondary hyperparathyroidism","volume":"6","author":"Steinl","year":"2021","journal-title":"Kidney Int Rep"},{"key":"B10","doi-asserted-by":"publisher","first-page":"1475","DOI":"10.1016\/j.kint.2017.12.014","article-title":"Incidence, predictors and therapeutic consequences of hypocalcemia in patients treated with cinacalcet in the EVOLVE trial","volume":"93","author":"Floege","year":"2018","journal-title":"Kidney Int"},{"key":"B11","doi-asserted-by":"publisher","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":"B12","doi-asserted-by":"publisher","first-page":"1079","DOI":"10.1016\/j.eprac.2024.08.004","article-title":"Improved clinical outcomes associated with hungry bone syndrome following parathyroidectomy in dialysis patients","volume":"30","author":"Silarat","year":"2024","journal-title":"Endocr Pract"},{"key":"B13","doi-asserted-by":"publisher","first-page":"21","DOI":"10.1007\/s13730-017-0284-z","article-title":"Hungry bone syndrome two weeks after starting cinacalcet: a call for caution","volume":"7","author":"Koubar","year":"2018","journal-title":"CEN Case Rep"},{"key":"B14","first-page":"583","article-title":"Hypophosphatemia and hungry bone syndrome in a dialysis patient with secondary hyperparathyroidism treated with cinacalcet\u2013proposal for an improved monitoring","volume":"52","author":"Nowack","year":"2006","journal-title":"Clin Lab"},{"key":"B15","doi-asserted-by":"publisher","first-page":"83","DOI":"10.1111\/j.1525-139X.2007.00248.x","article-title":"Cinacalcet-induced hungry bone syndrome","volume":"20","author":"Lazar","year":"2007","journal-title":"Semin Dial"},{"key":"B16","doi-asserted-by":"publisher","first-page":"111236","DOI":"10.1016\/j.mehy.2023.111236","article-title":"Partial primary osteoporosis maybe due to parathyroid hyperfunction caused by calcium intake insufficiency and\/or vitamin D insufficiency\/deficiency","volume":"182","author":"Qu","year":"2024","journal-title":"Med Hypotheses"},{"key":"B17","doi-asserted-by":"publisher","first-page":"153","DOI":"10.2535\/ofaj1936.78.5_153","article-title":"Effect of low calcium diet on the ultrastructure of the rat parathyroid gland","volume":"78","author":"Chen","year":"2001","journal-title":"Okajimas Folia Anat Jpn"},{"key":"B18","doi-asserted-by":"publisher","first-page":"599","DOI":"10.2215\/CJN.16601020","article-title":"Comparative effects of etelcalcetide and maxacalcitol on serum calcification propensity in secondary hyperparathyroidism: a randomized clinical trial","volume":"16","author":"Shoji","year":"2021","journal-title":"Clin J Am Soc Nephrol"},{"key":"B19","doi-asserted-by":"publisher","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":"B20","doi-asserted-by":"publisher","first-page":"637","DOI":"10.1093\/ndt\/gfad213","article-title":"Hypocalcemia and cardiovascular mortality in cinacalcet users","volume":"39","author":"Goto","year":"2024","journal-title":"Nephrol Dial Transplant"},{"key":"B21","doi-asserted-by":"publisher","first-page":"753","DOI":"10.1210\/endo-95-3-753","article-title":"Acute parathyroid hormone response: sensitivity, relationship to hypocalcemia, and rapidity","volume":"95","author":"Blum","year":"1974","journal-title":"Endocrinology"},{"key":"B22","doi-asserted-by":"publisher","first-page":"46","DOI":"10.1016\/j.mbs.2010.04.001","article-title":"A mathematical model of parathyroid hormone response to acute changes in plasma ionized calcium concentration in humans","volume":"226","author":"Shrestha","year":"2010","journal-title":"Math Biosci"},{"key":"B23","doi-asserted-by":"publisher","first-page":"2065","DOI":"10.1111\/j.1523-1755.2005.310_1.x","article-title":"High dialysate calcium may improve the efficacy of calcimimetic treatment in hemodialysis patients with severe secondary hyperparathyroidism","volume":"67","author":"Touam","year":"2005","journal-title":"Kidney Int"}],"container-title":["Frontiers in Medicine"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmed.2026.1907882\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T04:52:09Z","timestamp":1790743929000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmed.2026.1907882\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,30]]},"references-count":23,"alternative-id":["10.3389\/fmed.2026.1907882"],"URL":"https:\/\/doi.org\/10.3389\/fmed.2026.1907882","relation":{},"ISSN":["2296-858X"],"issn-type":[{"value":"2296-858X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,30]]},"article-number":"1907882"}}