Hormonal and mineral dysregulation determine the dynamics of calcification in adenine-induced CKD in male rats

in Journal of Endocrinology
Authors:
Beata Sieklucka Department of Monitored Pharmacotherapy, Medical University of Bialystok, Bialystok, Poland

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https://orcid.org/0000-0001-8384-7116
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Dariusz Pawlak Department of Pharmacodynamics, Medical University of Bialystok, Bialystok, Poland

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Małgorzata Galażyn-Sidorczuk Departament of Toxicology, Medical University of Bialystok, Bialystok, Poland

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Katarzyna Guzińska-Ustymowicz Department of General Pathomorphology, Medical University of Bialystok, Bialystok, Poland

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Anna Pryczynicz Department of General Pathomorphology, Medical University of Bialystok, Bialystok, Poland

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Magdalena Zabłudowska Department of Monitored Pharmacotherapy, Medical University of Bialystok, Bialystok, Poland

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Adam Płoński Department of Vascular Surgery and Transplantation, Medical University of Bialystok, Bialystok, Poland

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Krystyna Pawlak Department of Monitored Pharmacotherapy, Medical University of Bialystok, Bialystok, Poland

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Correspondence should be addressed to B Sieklucka: beata.sieklucka@umb.edu.pl
DOI:
https://doi.org/10.1530/JOE-25-0074
Volume/Issue:
Volume 265: Issue 3
Article Type:
Research Article
Article ID:
e250074
Online Publication Date:
03 Jun 2025
Copyright:
© the author(s) 2025
Restricted access
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Disturbances in calciotropic hormones: parathyroid hormone (PTH), vitamin D, fibroblast growth factor-23 (FGF-23)/Klotho, and mineral homeostasis are often seen in chronic kidney disease (CKD) and are key factors driving vascular calcification (VC). Importantly, the role of these hormones in VC is poorly understood. Therefore, we investigated how the dysregulation of calciotropic hormones and mineral metabolism determines the dynamics of the VC process in adenine-induced CKD in rats. Male rats were fed a diet containing 0.3% adenine for 4, 6, and 8 weeks to establish CKD. Classical markers of renal function, mineral homeostasis, and progression of VC were determined. In the earlier stages of CKD, in conditions of low 1,25-dihydroxyvitamin-D3 (1,25(OH)2D3) and Klotho deficiency, PTH exhibited an effective phosphaturic effect, and the PTH/FGF-23/Klotho axis seems to have a protective function against VC. In the later stage of the disease, the predominance of PTH led to the activation of 1,25(OH)2D3 synthesis, which resulted in the rebuilding of Klotho resources and allowed FGF-23 to take over a phosphaturic role. As a result, PTH/1,25(OH)2D3/Klotho signaling seems to exert a procalcifying effect. Moreover, VC was directly and inversely associated with the minerals excreted in the urine, and receiver operating characteristic analysis revealed a high diagnostic potential of calcium excretion in VC prediction. The present study shows that measuring serum panel of calciotropic hormones and urine tests assessing the excretion of minerals performed in a laboratory routine may be helpful tools for predicting VC progression at different CKD stages.

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Print ISSN:
0022-0795
Online ISSN:
1479-6805
Copyright:
© the author(s) 2025
Article ID:
e250074
Article Type:
Research Article
Received Date:
18 Feb 2025
Rev-recd:
15 May 2025
Accepted Date:
21 May 2025
Print Publication Date:
01 Jun 2025
Online Publication Date:
03 Jun 2025
Keywords:
vascular calcification; chronic kidney disease; parathyroid hormone; fibroblast growth factor-23; Klotho

  • Andrukhova O , Zeitz U , Goetz R , et al. 2012 FGF23 acts directly on renal proximal tubules to induce phosphaturia through activation of the ERK1/2-SGK1 signaling pathway. Bone 51 621–628. (https://doi.org/10.1016/j.bone.2012.05.015)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Andrukhova O , Smorodchenko A , Egerbacher M , et al. 2014 FGF23 promotes renal calcium reabsorption through the TRPV5 channel. EMBO J 33 229–246. (https://doi.org/10.1002/embj.20128418)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Andrukhova O , Streicher C , Zeitz U , et al. 2016 Fgf23 and parathyroid hormone signaling interact in kidney and bone. Mol Cell Endocrinol 436 224–239. (https://doi.org/10.1016/j.mce.2016.07.035)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Armbrecht HJ , Boltz MA , Ritter CS , et al. 2007 Parathyroid hormone stimulation of the renal 25-hydroxyvitamin D-1α-hydroxylase-Effect of age and free radicals. J Steroid Biochem Mol Biol 103 330–333. (https://doi.org/10.1016/j.jsbmb.2006.12.035)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Bacic D , Lehir M , Biber J , et al. 2006 The renal Na+/phosphate cotransporter NaPi-IIa is internalized via the receptor-mediated endocytic route in response to parathyroid hormone. Kidney Int 69 495–503. (https://doi.org/10.1038/sj.ki.5000148)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • van Ballegooijen AJ , Reinders I , Visser M , et al. 2013 Parathyroid hormone and cardiovascular disease events: a systematic review and meta-analysis of prospective studies. Am Heart J 165 655–664.e5. (https://doi.org/10.1016/j.ahj.2013.02.014)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Chang Q , Hoefs S , van der Kemp AW , et al. 2005 Cell signalling: the β-glucuronidase klotho hydrolyzes and activates the TRPV5 channel. Science 310 490–493. (https://doi.org/10.1126/science.1114245)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Cozzolino M , Dusso AS , Liapis H , et al. 2002 The effects of sevelamer hydrochloride and calcium carbonate on kidney calcification in uremic rats. J Am Soc Nephrol 13 2299–2308. (https://doi.org/10.1097/01.ASN.0000025782.24383.0D)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Diwan V , Small D , Kauter K , et al. 2014 Gender differences in adenine-induced chronic kidney disease and cardiovascular complications in rats. Am J Physiol Ren Physiol 307 F1169–F1178. (https://doi.org/10.1152/ajprenal.00676.2013)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Fishbane SN & Nigwekar S 2021 Phosphate absorption and hyperphosphatemia management in kidney disease: a physiology-based review. Kidney Med 3 1057–1064. (https://doi.org/10.1016/j.xkme.2021.07.003)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Forster RE , Jurutka PW , Hsieh JC , et al. 2011 Vitamin D receptor controls expression of the anti-aging klotho gene in mouse and human renal cells. Biochem Biophys Res Commun 414 557–562. (https://doi.org/10.1016/j.bbrc.2011.09.117)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Frazão JM & Adragão T 2008 Treatment of hyperphosphatemia with sevelamer hydrochloride in dialysis patients: effects on vascular calcification, bone and a close look into the survival data. Kidney Int 74 38–43. (https://doi.org/10.1038/ki.2008.544)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Geller JL , Khosravi A , Kelly MH , et al. 2007 Clinical vignette: cinacalcet in the management of tumor-induced osteomalacia. J Bone Miner Res 22 931–937. (https://doi.org/10.1359/jbmr.070304)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Giachelli CM 2009 The emerging role of phosphate in vascular calcification. Kidney Int 75 890–897. (https://doi.org/10.1038/ki.2008.644)

  • Giachelli CM , Speer MY , Li X , et al. 2005 Regulation of vascular calcification: roles of phosphate and osteopontin. Circ Res 96 717–722. (https://doi.org/10.1161/01.RES.0000161997.24797.c0)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Gutierrez O , Isakova T , Rhee E , et al. 2005 Fibroblast growth factor-23 mitigates hyperphosphatemia but accentuates calcitriol deficiency in chronic kidney disease. J Am Soc Nephrol 16 2205–2215. (https://doi.org/10.1681/ASN.2005010052)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Haussler MR , Haussler CA , Whitfield GK , et al. 2010 The nuclear vitamin D receptor controls the expression of genes encoding factors which feed the “fountain of youth” to mediate healthful aging. J Steroid Biochem Mol Biol 121 88–97. (https://doi.org/10.1016/j.jsbmb.2010.03.019)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Haussler MR , Livingston S , Sabir ZL , et al. 2021 Vitamin D receptor mediates a myriad of biological actions dependent on its 1,25-dihydroxyvitamin D ligand: distinct regulatory themes revealed by induction of klotho and fibroblast growth factor-23. JBMR Plus 5 1–21. (https://doi.org/10.1002/jbm4.10432)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Hill NR , Fatoba ST , Oke JL , et al. 2016 Global prevalence of chronic kidney disease – a systematic review and meta-analysis. PLoS One 11 e0158765. (https://doi.org/10.1371/journal.pone.0158765)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Hu MC , Shi M , Zhang J , et al. 2010 Klotho: a novel phosphaturic substance acting as an autocrine enzyme in the renal proximal tubule. FASEB J 24 3438–3450. (https://doi.org/10.1096/fj.10-154765)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Hu MC , Shi M , Zhang J , et al. 2011 Klotho deficiency causes vascular calcification in chronic kidney disease. J Am Soc Nephrol 22 124–136. (https://doi.org/10.1681/ASN.2009121311)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Ide N , Olauson H , Sato T , et al. 2016 In vivo evidence for a limited role of proximal tubular Klotho in renal phosphate handling. Kidney Int 90 348–362. (https://doi.org/10.1016/j.kint.2016.04.009)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Isakova T , Wahl P , Vargas GS , et al. 2011 Fibroblast growth factor 23 is elevated before parathyroid hormone and phosphate in chronic kidney disease. Kidney Int 79 1370–1378. (https://doi.org/10.1038/ki.2011.47)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Jean G , Bresson E , Terrat JC , et al. 2009 Peripheral vascular calcification in long-haemodialysis patients: associated factors and survival consequences. Nephrol Dial Transplant 24 948–955. (https://doi.org/10.1093/ndt/gfn571)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Kakani E , Elyamny M , Ayach T , et al. 2019 Pathogenesis and management of vascular calcification in CKD and dialysis patients. Semin Dial 32 553–561. (https://doi.org/10.1111/sdi.12840)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Kalpakian MA & Mehrotra R 2007 Vascular calcification and disordered mineral metabolism in dialysis patients. Semin Dial 20 139–143. (https://doi.org/10.1111/j.1525-139X.2007.00261.x)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Kashioulis P , Lundgren J , Shubbar E , et al. 2018 Adenine-induced chronic renal failure in rats: a model of chronic renocardiac syndrome with left ventricular diastolic dysfunction but preserved ejection fraction. Kidney Blood Press Res 43 1053–1064. (https://doi.org/10.1159/000491056)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Kendrick J , Cheung AK , Kaufman JS , et al. 2011 FGF-23 associates with death, cardiovascular events, and initiation of chronic dialysis. J Am Soc Nephrol 22 1913–1922. (https://doi.org/10.1681/ASN.2010121224)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Ketteler M & Biggar PH 2013 Use of phosphate binders in chronic kidney disease. Curr Opin Nephrol Hypertens 22 413–420. (https://doi.org/10.1097/MNH.0b013e32836214d4)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Kocełak P , Puzianowska-Kuźnicka M , Olszanecka-Glinianowicz M , et al. 2024 Wnt signaling pathway and sclerostin in the development of atherosclerosis and vascular calcification. Adv Clin Exp Med 33 519–532. (https://doi.org/10.17219/acem/169567)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Kuro-o M , Matsumura Y , Aizawa H , et al. 1997 Mutation of the mouse klotho gene leads to a syndrome resembling ageing. Nature 390 45–51. (https://doi.org/10.1038/36285)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Lee YT , Ng HY , Chiu TT , et al. 2016 Association of bone-derived biomarkers with vascular calcification in chronic hemodialysis patients. Clin Chim Acta 452 38–43. (https://doi.org/10.1016/j.cca.2015.10.031)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Leung J & Crook M 2019 Disorders of phosphate metabolism. J Clin Pathol 72 741–747. (https://doi.org/10.1136/jclinpath-2018-205130)

  • Lim K , Lu TS , Molostvov G , et al. 2012 Vascular klotho deficiency potentiates the development of human artery calcification and mediates resistance to fibroblast growth factor 23. Circulation 125 2243–2255. (https://doi.org/10.1161/CIRCULATIONAHA.111.053405)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Lindberg K , Amin R , Moe OW , et al. 2014 The kidney is the principal organ mediating Klotho effects. J Am Soc Nephrol 25 2169–2175. (https://doi.org/10.1681/ASN.2013111209)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Lishmanov A , Dorairajan S , Pak Y , et al. 2012 Elevated serum parathyroid hormone is a cardiovascular risk factor in moderate chronic kidney disease. Int Urol Nephrol 44 541–547. (https://doi.org/10.1007/s11255-010-9897-2)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Liu J , Tio MC , Verma A , et al. 2022 Determinants and outcomes associated with urinary calcium excretion in chronic kidney disease. J Clin Endocrinol Metab 107 E281–E292. (https://doi.org/10.1210/clinem/dgab574)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Mace ML , Gravesen E , Nordholm A , et al. 2018 Fibroblast growth factor (FGF) 23 regulates the plasma levels of parathyroid hormone in vivo through the FGF receptor in normocalcemia, but not in hypocalcemia. Calcif Tissue Int 102 85–92. (https://doi.org/10.1007/s00223-017-0333-9)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Mehrotra R & Adler S 2005 Coronary artery calcification in nondialyzed patients with chronic kidney diseases. Am J Kidney Dis 45 963. (https://doi.org/10.1053/j.ajkd.2005.01.041)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Mizobuchi M , Towler D & Slatopolsky E 2009 Vascular calcification: the killer of patients with chronic kidney disease. J Am Soc Nephrol 20 1453–1464. (https://doi.org/10.1681/ASN.2008070692)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Nasrallah MM , El-Shehaby AR , Salem MM , et al. 2010 Fibroblast growth factor-23 (FGF-23) is independently correlated to aortic calcification in haemodialysis patients. Nephrol Dial Transplant 25 2679–2685. (https://doi.org/10.1093/ndt/gfq089)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Neven E , Bashir-Dar R , Dams G , et al. 2015 Disturbances in bone largely predict aortic calcification in an alternative rat model developed to study both vascular and bone pathology in chronic kidney disease. J Bone Miner Res 30 2313–2324. (https://doi.org/10.1002/jbmr.2585)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Palit S & Kendrick J 2014 Vascular calcification in chronic kidney disease: role of disordered mineral metabolism. Curr Pharm Des 20 5829–5833. (https://doi.org/10.2174/1381612820666140212194926)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Pasquali M , Tartaglione L , Rotondi S , et al. 2015 Calcitriol/calcifediol ratio: an indicator of vitamin D hydroxylation efficiency? BBA Clin 3 251–256. (https://doi.org/10.1016/j.bbacli.2015.03.004)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Pawlak D , Znorko B , Kalaska B , et al. 2018 LP533401 restores bone health in 5/6 nephrectomized rats by a decrease of gut-derived serotonin and regulation of serum phosphate through the inhibition of phosphate co-transporters expression in the kidneys. Bone 113 124–136. (https://doi.org/10.1016/j.bone.2018.05.022)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Pawlak D , Domaniewski T , Znorko B , et al. 2019 The use of LP533401 as a therapeutic option for renal osteodystrophy affects, renal calcium handling, vitamin D metabolism, and bone health in uremic rats. Expert Opin Ther Targets 23 8222. (https://doi.org/10.1080/14728222.2019.1586883)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Qureshi AR , Olauson H , Witasp A , et al. 2015 Increased circulating sclerostin levels in end-stage renal disease predict biopsy-verified vascular medial calcification and coronary artery calcification. Kidney Int 88 1356–1364. (https://doi.org/10.1038/ki.2015.194)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Raggi P , Boulay A , Chasan-Taber S , et al. 2002 Cardiac calcification in adult hemodialysis patients: a link between end-stage renal disease and cardiovascular disease? J Am Coll Cardiol 39 695–701. (https://doi.org/10.1016/S0735-1097(01)01781-8)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Ravani P , Malberti F , Tripepi G , et al. 2009 Vitamin D levels and patient outcome in chronic kidney disease. Kidney Int 75 88–95. (https://doi.org/10.1038/ki.2008.501)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Sakan H , Nakatani K , Asai O , et al. 2014 Reduced renal α-Klotho expression in CKD patients and its effect on renal phosphate handling and vitamin D metabolism. PLoS One 9 e86301. (https://doi.org/10.1371/journal.pone.0086301)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Scialla JJ , Lau WL , Reilly MP , et al. 2013 Fibroblast growth factor 23 is not associated with and does not induce arterial calcification. Kidney Int 83 1159–1168. (https://doi.org/10.1038/ki.2013.3)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Segawa H , Yamanaka S , Onitsuka A , et al. 2007 Parathyroid hormone-dependent endocytosis of renal type IIc Na-Pi cotransporter. Am J Physiol Ren Physiol 292 395–403. (https://doi.org/10.1152/ajprenal.00100.2006)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Shigematsu T , Kazama JJ , Yamashita T , et al. 2004 Possible involvement of circulating fibroblast growth factor 23 in the development of secondary hyperparathyroidism associated with renal insufficiency. Am J Kidney Dis 44 250–256. (https://doi.org/10.1053/j.ajkd.2004.04.029)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Shimada T , Hasegawa H , Yamazaki Y , et al. 2004 FGF-23 is a potent regulator of vitamin D metabolism and phosphate homeostasis. J Bone Miner Res 19 429–435. (https://doi.org/10.1359/JBMR.0301264)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Shimamura Y , Hamada K , Inoue K , et al. 2012 Serum levels of soluble secreted a-Klotho are decreased in the early stages of chronic kidney disease, making it a probable novel biomarker for early diagnosis. Clin Exp Nephrol 16 722–729. (https://doi.org/10.1007/s10157-012-0621-7)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Shobeiri N , Pang J , Adams MA , et al. 2013 Cardiovascular disease in an adenine-induced model of chronic kidney disease: the temporal link between vascular calcification and haemodynamic consequences. J Hypertens 31 160–168. (https://doi.org/10.1097/HJH.0b013e32835b15bb)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Smith ER , Hewitson TD & Holt SG 2019 Diagnostic tests for vascular calcification. Adv Chron Kidney Dis 26 445–463. (https://doi.org/10.1053/j.ackd.2019.07.001)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Souberbielle JCP , Roth H & Fouque DP 2010 Parathyroid hormone measurement in CKD. Kidney Int 77 93–100. (https://doi.org/10.1038/ki.2009.374)

  • Tobias JH 2023 Sclerostin and cardiovascular disease. Curr Osteoporos Rep 21 519–526. (https://doi.org/10.1007/s11914-023-00810-w)

  • Viaene L , Meijers BK , Vanrenterghem Y , et al. 2012 Evidence in favor of a severely impaired net intestinal calcium absorption in patients with (early-stage) chronic kidney disease. Am J Nephrol 35 434–441. (https://doi.org/10.1159/000338299)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Wu M , Rementer C & Giachelli CM 2013 Vascular calcification: an update on mechanisms and challenges in treatment. Calcif Tissue Int 93 365–373. (https://doi.org/10.1007/s00223-013-9712-z)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Yamada S & Giachelli CM 2017 Vascular calcification in CKD-MBD: roles for phosphate, FGF23, and klotho. Bone 100 87–93. (https://doi.org/10.1016/j.bone.2016.11.012)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Yamada S , Tatsumoto N , Tokumoto M , et al. 2015 Phosphate binders prevent phosphate-induced cellular senescence of vascular smooth muscle cells and vascular calcification in a modified, adenine-based uremic rat model. Calcif Tissue Int 96 347–358. (https://doi.org/10.1007/s00223-014-9929-5)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Yeung WCG , Palmer SC , Strippoli GFM , et al. 2023 Vitamin D therapy in adults with CKD: a systematic review and meta-analysis. Am J Kidney Dis 82 543–558. (https://doi.org/10.1053/j.ajkd.2023.04.003)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Yuan Q , Sato T , Densmore M , et al. 2011 FGF-23/Klotho signaling is not essential for the phosphaturic and anabolic functions of PTH. J Bone Miner Res 26 2026–2035. (https://doi.org/10.1002/jbmr.433)

    • PubMed
    • Search Google Scholar
    • Export Citation