Ruolo del citrato nel metabolismo osseo

  • Giuseppe Vezzoli Unità di Nefrologia e Dialisi, IRCCS Ospedale San Raffaele, Scuola di Specializzazione in Nefrologia, Università Vita Salute San Raffaele, Milano - Italia
  • Giulia Magni Unità di Nefrologia e Dialisi, IRCCS Ospedale San Raffaele, Scuola di Specializzazione in Nefrologia, Università Vita Salute San Raffaele, Milano - Italia
  • Monica Avino Unità di Nefrologia e Dialisi, IRCCS Ospedale San Raffaele, Scuola di Specializzazione in Nefrologia, Università Vita Salute San Raffaele, Milano - Italia
  • Teresa Arcidiacono Unità di Nefrologia e Dialisi, IRCCS Ospedale San Raffaele, Scuola di Specializzazione in Nefrologia, Università Vita Salute San Raffaele, Milano - Italia
Parole chiave: Citrato, Citraturia, Ipocitraturia, Rimodellamento osseo

Abstract

Citrate is an organic compound involved in tricarboxylic acid cycle, regulation of acid-base balance, lipid metabolism and bone formation. The 90% of body citrate is deposited in bone tissue and is released with calcium ions during bone resorption; therefore, bone resorption contributes to maintain normal plasma levels of citrate together with kidney excretion. The parallel release of citrate and calcium from bones decreases the possibility of calcium-phosphate precipitation in soft tissues, as citrate can bind calcium ions in organic fluids. Citrate may also take part to the bone formation as it sustains the correct mineralization of bone organic matrix: its molecule binds calcium ions at the surface of hydroxyapatite nanocrystals and maintains the correct spatial disposition of nanocrystals, thus, stabilizing the structure of bone lamellae and sustaining biomechanical characteristics of bone tissue. Multiple studies observed that citrate administration significantly increased areal and volumetric bone mineral density at different locations of 1-2% per year and improved bone resorption markers as well. Therefore, it has been hypothesised a therapeutic role of citrate in osteoporosis; however, this role has to be better clarified to understand its real anti-fracture effect.

Riferimenti bibliografici

Caudarella R, Vescini F, Buffa A, Stefoni S. Citrate and mineral metabolism: kidney stones and bone metabolism. Front Bioscience 2003;8:s1084-1106.

Kaufman AM, Kahn T. Complementary role of citrate and bicarbonate excretion in acid-base balance in the rat. Am J Physiol 1988;255:F182-F187.

Simpson DP. Citrate excretion: a window on renal metabolism. Am J Physiol. 1983;244:F223-F234.

Goraya N, Simoni J, Sager LN, et al. Urine citrate excretion as a marker of acid retention in patients with chronic kidney disease without overt metabolic acidosis. Kidney Int 2019;95:1190-1196.

Brown JC, Packer RK, Knepper MA. Role of organic anions in renal response to dietary acid and base loads. Am J Physiol. 1989;257:F170-F176.

Costello LC, Franklin RB. Plasma citrate homeostasis: How it is regulated; and its physiological and clinical implications. An important, but neglected, relationship in medicine. HSOA J Hum Endocrinol 2016;1;pii: 005.

Kang DE, Sur RL, Haleblian GE, et al. Long-term lemonade based dietary manipulation in patients with hypocitraturic nephrolithiasis. J Urol 2007;177:1358-1362.

Ivanchenko P, Delgado-López JM, Iafisco M, et al. On the surface effects of citrates on nano-apatites: evidence of a decreased hydrophilicity. Sci Rep 2017;7:8901.

Costello LC, Chellaiah M, Zou J, Franklin RB, Reynolds MA. The status of citrate in the hydroxyapatite/collagen complex of bone; and Its role in bone formation. J Regen Med Tissue Eng 2015;3:4.

Kenny A, Draskczy P, Goldhaber P. Citric acid production by resorbing bone in tissue culture. Am J Physiol. 1959;197:502-504.

Dixon TF, Perkins HR. Citric acid and bone metabolism. Biochem J. 1952;52:260-265.

Fu X, Li Y, Huang T, et al. Runx2/Osterix and zinc uptake synergize to orchestrate osteogenic differentiation and citrate containing bone apatite formation. Adv Sci 2018;5:1700755.

Chen H, Wang Y, Dai H, et al. Bone and plasma citrate is reduced in osteoporosis. Bone 2018;114:189-197.

Herzberg M, Foldes J, Steinberg R, Menczel J. Zinc excretion in osteoporotic women. J Bone Miner Res 1990;5:251-257.

M. Yamaguchi, M. Goto, S. Uchiyama, T. Nakagawa. Effect of zinc on gene expression in osteoblastic MC3T3-E1 cells: enhancement of Runx2, OPG, and regucalcin mRNA expressions. Mol Cell Biochem 2008;312:157-166.

Hu YY, Rawal A, Schmidt-Rohr K. Strongly bound citrate stabilizes the apatite nanocrystals in bone. Proc Natl Acad Sci USA 2010;107:22425-22429.

Davies E, Müller KH, Wong WC. Citrate bridges between mineral platelets in bone. Proc Natl Acad Sci USA 2014;111: E1354-E1363.

Ivanchenko P, Delgado-López JM, Iafisco M, et al. On the surface effects of citrates on nano-apatites: evidence of a decreased hydrophilicity. Sci Rep 2017;7:8901.

Irizarry AR, Yan G, Zeng Q. Defective enamel and bone development in sodium-dependent citrate transporter (NaCT) Slc13a5 deficient mice. PLoS ONE 2017;12:e0175465.

Caudarella R, Miniero R, Rizzoli E, et al. Urinary citrate excretion in healthy women before and after menopause. Ital J Mineral Electrolyte Metab 1995;9:31-38.

Jehle S, Hulter HN, Krapf R. Effect of potassium citrate on bone density, microarchitecture, and fracture risk in healthy older adults without osteoporosis: a randomized controlled trial. J Clin Endocrinol Metab 2013;98:207-217.

Vescini F, Buffa A, La Manna G, et al. Long-term potassium citrate therapy and bone mineral density in idiopathic calcium stone formers. J Endocrinol Invest 2005;28:218-222.

Jehle S, Zanetti A, Muser J, et al. Partial neutralization of the acidogenic western diet with potassium citrate increases bone mass in postmenopausal women with osteopenia. J Am Soc Nephrol 2006;17:3213-3222.

Marangella M, Di Stefano M, Casalis S, Berutti S, D’Amelio P, Isaia GC. Effects of potassium citrate supplementation on bone metabolism. Calcif Tissue Int 2004;74:330-335.

Gregory NS, Kumar R, Stein EM, Alexander E, Christos P, Bockman RS, Rodman JS. Potassium citrate decreases bone resorption in postmenopausal women with osteopenia: A randomized double-blind clinical trial. Endocr Pract 2015;21:1380-1386.

Sebastian A, Harris ST, Ottaway JH, et al. Improved mineral balance and skeletal metabolism in postmenopausal women treated with potassium bicarbonate. N Engl J Med 1994;330:1776-1781.

Nielsen TT, Sorensen NS. Citrate in plasma and urine during total fasting. Acta Med Scand 1979;205:303-307.

Marangella M, Vitale C, Manganaro M, et al. Renal handling of citrate in chronic renal insufficiency. Nephron 1991;57:439-443.

Fraenkl SA, Muser J, Groell R, et al. Plasma citrate levels as a potential biomarker for glaucoma. J Ocul Pharmacol Ther 2011;27:577-580.

Tiselius HG, Berg C, Fornander AM, Nilsson MA. Effects of citrate on the different phases of calcium oxalate crystallization. Scanning Microsc 1993;7:381-390.

Phillips R, Hanchanale VS, Myatt A, Somani B, Nabi G, Biyani CS. Citrate salts for preventing and treating calcium containing kidney stones in adults. Cochrane Database Syst Rev 2015;(10):CD010057.

Granchi D, Torreggiani E, Massa A, Caudarella R, Di Pompo G, Baldini N. Potassium citrate prevents increased osteoclastogenesis resulting from acidic conditions: Implication for the treatment of post-menopausal bone loss. PLoS One 2017;12:e0181230.

Pubblicato
2020-02-20
Sezione
Review