Expression of Fibroblast Growth Factor 23, Vitamin D Receptor, and Sclerostin in Bone Tissue from Hypercalciuric Stone Formers

Overview

Journal Clin J Am Soc Nephrol

Specialty Nephrology

Date 2014 Apr 26

PMID 24763863

Citations 12

Authors

Viviane Barcellos Menon

Rosa Maria Affonso Moyses

Samirah Abreu Gomes

Aluizio Barbosa de Carvalho

Vanda Jorgetti

Ita Pfeferman Heilberg

Affiliations

Soon will be listed here.

Abstract

Background And Objectives: Increased bone resorption, low bone formation, and abnormal mineralization have been described in stone formers with idiopathic hypercalciuria. It has been previously shown that the receptor activator of NF-κB ligand mediates bone resorption in idiopathic hypercalciuria (IH). The present study aimed to determine the expression of fibroblast growth factor 23 (FGF-23), vitamin D receptor (VDR), and sclerostin in bone tissue from IH stone formers.

Design, Setting, Participants, & Measurements: Immunohistochemical analysis was performed in undecalcified bone samples previously obtained for histomorphometry from 30 transiliac bone biopsies of idiopathic hypercalciuria stone-forming patients between 1992 and 2002 and 33 healthy individuals (controls). Serum parameters were obtained from their medical records.

Results: Histomorphometry disclosed 21 IH patients with high and 9 IH patients with normal bone resorption. Importantly, eroded surfaces (ES/BS) from IH patients but not controls were significantly correlated with VDR immunostaining in osteoblasts (r=0.51; P=0.004), sclerostin immunostaining in osteocytes (r=0.41; P=0.02), and serum 1,25-dihydroxyvitamin D (r=0.55; P<0.01). Of note, both VDR and sclerostin immunostaining were significantly correlated with serum 1,25-dihydroxyvitamin D in IH patients (r=0.52; P=0.01 and r=0.53; P=0.02, respectively), although VDR and sclerostin expression did not differ between IH and controls. IH patients with high bone resorption exhibited a significantly stronger sclerostin immunostaining than IH patients with normal bone resorption. FGF-23 expression in osteocytes from IH patients did not differ from controls and was not correlated with any histomorphometric parameter.

Conclusions: These findings suggest the contribution of VDR and sclerostin, as well as 1,25-dihydroxyvitamin D, to increase bone resorption in idiopathic hypercalciuria but do not implicate FGF-23 in the bone alterations seen in these patients.

Citing Articles

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Serum sclerostin is associated with recurrent kidney stone formation independent of hypercalciuria.

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Urinary Calcium Is Associated with Serum Sclerostin among Stone Formers.

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Rodrigues F, Neves R, Ormanji M, Esper P, Gaspar M, Pereira R J Pers Med. 2022; 12(7).

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Beta-thalassaemia major: Prevalence, risk factors and clinical consequences of hypercalciuria.

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PMID: 35768889 PMC: 9542302. DOI: 10.1111/bjh.18345.

References

Malluche H, Tschoepe W, Ritz E, Meyer-Sabellek W, Massry S . Abnormal bone histology in idiopathic hypercalciuria. J Clin Endocrinol Metab. 1980; 50(4):654-8. DOI: 10.1210/jcem-50-4-654. View

Gaudio A, Pennisi P, Bratengeier C, Torrisi V, Lindner B, Mangiafico R . Increased sclerostin serum levels associated with bone formation and resorption markers in patients with immobilization-induced bone loss. J Clin Endocrinol Metab. 2010; 95(5):2248-53. DOI: 10.1210/jc.2010-0067. View

Zerwekh J, Reed B, Heller H, Gonzalez G, Haussler M, Pak C . Normal vitamin D receptor concentration and responsiveness to 1, 25-dihydroxyvitamin D3 in skin fibroblasts from patients with absorptive hypercalciuria. Miner Electrolyte Metab. 1998; 24(5):307-13. DOI: 10.1159/000057388. View

Moester M, Papapoulos S, Lowik C, Van Bezooijen R . Sclerostin: current knowledge and future perspectives. Calcif Tissue Int. 2010; 87(2):99-107. PMC: 2903685. DOI: 10.1007/s00223-010-9372-1. View

Pacifici R, ROTHSTEIN M, Rifas L, Lau K, Baylink D, Avioli L . Increased monocyte interleukin-1 activity and decreased vertebral bone density in patients with fasting idiopathic hypercalciuria. J Clin Endocrinol Metab. 1990; 71(1):138-45. DOI: 10.1210/jcem-71-1-138. View

Ryan J, Reinke D, Kogawa M, Turner A, Atkins G, Anderson P . Novel targets of vitamin D activity in bone: action of the vitamin D receptor in osteoblasts, osteocytes and osteoclasts. Curr Drug Targets. 2013; 14(14):1683-8. DOI: 10.2174/138945011131400212. View

Steiniche T, Mosekilde L, Christensen M, Melsen F . A histomorphometric determination of iliac bone remodeling in patients with recurrent renal stone formation and idiopathic hypercalciuria. APMIS. 1989; 97(4):309-16. DOI: 10.1111/j.1699-0463.1989.tb00793.x. View

Nakashima T, Hayashi M, Fukunaga T, Kurata K, Oh-Hora M, Feng J . Evidence for osteocyte regulation of bone homeostasis through RANKL expression. Nat Med. 2011; 17(10):1231-4. DOI: 10.1038/nm.2452. View

Rendina D, Mossetti G, DE Filippo G, Cioffi M, Strazzullo P . Fibroblast growth factor 23 is increased in calcium nephrolithiasis with hypophosphatemia and renal phosphate leak. J Clin Endocrinol Metab. 2005; 91(3):959-63. DOI: 10.1210/jc.2005-1606. View

10.

Atkins G, Findlay D . Osteocyte regulation of bone mineral: a little give and take. Osteoporos Int. 2012; 23(8):2067-79. DOI: 10.1007/s00198-012-1915-z. View

11.

Ferreira L, Pereira A, Heilberg I . Vitamin D receptor and calcium-sensing receptor gene polymorphisms in hypercalciuric stone-forming patients. Nephron Clin Pract. 2009; 114(2):c135-44. DOI: 10.1159/000254386. View

12.

Heilberg I, Martini L, Szejnfeld V, Carvalho A, Draibe S, AJZEN H . Bone disease in calcium stone forming patients. Clin Nephrol. 1994; 42(3):175-82. View

13.

Li X, Tembe V, Horwitz G, Bushinsky D, Favus M . Increased intestinal vitamin D receptor in genetic hypercalciuric rats. A cause of intestinal calcium hyperabsorption. J Clin Invest. 1993; 91(2):661-7. PMC: 288005. DOI: 10.1172/JCI116246. View

14.

Durosier C, van Lierop A, Ferrari S, Chevalley T, Papapoulos S, Rizzoli R . Association of circulating sclerostin with bone mineral mass, microstructure, and turnover biochemical markers in healthy elderly men and women. J Clin Endocrinol Metab. 2013; 98(9):3873-83. DOI: 10.1210/jc.2013-2113. View

15.

Melsen F, Mosekilde L . Tetracycline double-labeling of iliac trabecular bone in 41 normal adults. Calcif Tissue Res. 1978; 26(2):99-102. DOI: 10.1007/BF02013242. View

16.

Lieben L, Masuyama R, Torrekens S, Van Looveren R, Schrooten J, Baatsen P . Normocalcemia is maintained in mice under conditions of calcium malabsorption by vitamin D-induced inhibition of bone mineralization. J Clin Invest. 2012; 122(5):1803-15. PMC: 3336970. DOI: 10.1172/JCI45890. View

17.

Wang H, Yoshiko Y, Yamamoto R, Minamizaki T, Kozai K, Tanne K . Overexpression of fibroblast growth factor 23 suppresses osteoblast differentiation and matrix mineralization in vitro. J Bone Miner Res. 2008; 23(6):939-48. DOI: 10.1359/jbmr.080220. View

18.

Worcester E, Coe F . New insights into the pathogenesis of idiopathic hypercalciuria. Semin Nephrol. 2008; 28(2):120-32. PMC: 2362396. DOI: 10.1016/j.semnephrol.2008.01.005. View

19.

Gomes S, Dos Reis L, de Oliveira I, Noronha I, Jorgetti V, Heilberg I . Usefulness of a quick decalcification of bone sections embedded in methyl methacrylate[corrected]: an improved method for immunohistochemistry. J Bone Miner Metab. 2007; 26(1):110-3. DOI: 10.1007/s00774-007-0788-2. View

20.

McClung M, Grauer A, Boonen S, Bolognese M, Brown J, Diez-Perez A . Romosozumab in postmenopausal women with low bone mineral density. N Engl J Med. 2014; 370(5):412-20. DOI: 10.1056/NEJMoa1305224. View