Advances in the understanding of mineral and bone metabolism in inflammatory bowel diseases

American Journal of Physiology - Gastrointestinal and Liver Physiology

Volumn 300, Issue 2, 2011, Pages

  Ghishan, Fayez K ^a   Kiela, Pawel R ^a,b  

^a UNIVERSITY OF ARIZONA COLLEGE OF MEDICINE   (United States)

^b UNIVERSITY OF ARIZONA   (United States)

Author keywords

Bone mineral density; Crohn's disease; Osteopenia; Osteoporosis; Ulcerative colitis

Indexed keywords

ANABOLIC AGENT; CALCIUM ION; CORTICOSTEROID; CYTOKINE RECEPTOR ANTAGONIST; INFLIXIMAB; INTERLEUKIN 1BETA; INTERLEUKIN 6; KLOTHO PROTEIN; MENAQUINONE; OSTEOCLAST DIFFERENTIATION FACTOR; PHOSPHATE; PHYTOMENADIONE; STEROID; TUMOR NECROSIS FACTOR; VITAMIN D; VITAMIN K GROUP; WARFARIN;

BONE METABOLISM; BONE REMODELING; CALCIUM ABSORPTION; CALCIUM CELL LEVEL; CALCIUM HOMEOSTASIS; CALCIUM TRANSPORT; COLITIS; CROHN DISEASE; DEEP VEIN THROMBOSIS; ENTERITIS; HUMAN; IMMUNOMODULATION; INFLAMMATION; INFLAMMATORY DISEASE; MALABSORPTION; MEDIATOR; MEDIATOR RELEASE; MINERAL METABOLISM; NONHUMAN; OSSIFICATION; OSTEOBLAST; OSTEOCLAST; OSTEOLYSIS; OSTEOPENIA; OSTEOPOROSIS; PHOSPHATE METABOLISM; PRIORITY JOURNAL; REVIEW; STEROID THERAPY; TREATMENT FAILURE; ULCERATIVE COLITIS; VITAMIN D DEFICIENCY; VITAMIN SUPPLEMENTATION;

ANIMALS; BONE DISEASES, METABOLIC; CALCIFICATION, PHYSIOLOGIC; CALCIUM; COLITIS, ULCERATIVE; CROHN DISEASE; GASTROENTEROLOGY; HOMEOSTASIS; HORMONES; HUMANS; IMMUNOLOGIC FACTORS; INFLAMMATION MEDIATORS; METABOLISM; OSTEOBLASTS; OSTEOCLASTS; OSTEOPOROSIS; PHOSPHATES; SIGNAL TRANSDUCTION; VITAMIN D;

EID: 79251565517     PISSN: 01931857     EISSN: 15221547     Source Type: Journal    
DOI: 10.1152/ajpgi.00496.2010     Document Type: Review

References (110)

1. Abreu MT, Kantorovich V, Vasiliauskas EA, Gruntmanis U, Matuk R, Daigle K, Chen S, Zehnder D, Lin YC, Yang H, Hewison M, Adams JS. Measurement of vitamin D levels in inflammatory bowel disease patients reveals a subset of Crohn's disease patients with elevated 1,25-dihydroxyvitamin D and low bone mineral density. Gut 53: 1129-1136, 2004. (Pubitemid 38961967)
2. Airaksinen MS, Eilers J, Garaschuk O, Thoenen H, Konnerth A, Meyer M. Ataxia and altered dendritic calcium signaling in mice carrying a targeted null mutation of the calbindin D28k gene. Proc Natl Acad Sci USA 94: 1488-1493, 1997. (Pubitemid 27087878)
3. Akhter MP, Jung LK. Decreased bone strength in HLA-B27 transgenic rat model of spondyloarthropathy. Rheumatology (Oxford) 46: 1258-1262, 2007.
4. 2+ absorption in small intestine. Arch Biochem Biophys 460: 227-232, 2007.
5. Alexander RT, Woudenberg-Vrenken TE, Buurman J, Dijkman H, van der Eerden BC, van Leeuwen JP, Bindels RJ, Hoenderop JG. Klotho prevents renal calcium loss. J Am Soc Nephrol 20: 2371-2379, 2009.
6. Ali T, Lam D, Bronze MS, Humphrey MB. Osteoporosis in inflammatory bowel disease. Am J Med 122: 599-604, 2009.
7. American Gastroenterological Association medical position statement: guidelines on osteoporosis in gastrointestinal diseases. Gastroenterology 124: 791-794, 2003. (Pubitemid 36268495)
8. Ardizzone S, Bollani S, Bettica P, Bevilacqua M, Molteni P, Bianchi Porro G. Altered bone metabolism in inflammatory bowel disease: there is a difference between Crohn's disease and ulcerative colitis. J Intern Med 247: 63-70, 2000. (Pubitemid 30073165)
9. Ashcroft AJ, Cruickshank SM, Croucher PI, Perry MJ, Rollinson S, Lippitt JM, Child JA, Dunstan C, Felsburg PJ, Morgan GJ, Carding SR. Colonic dendritic cells, intestinal inflammation, and T cell-mediated bone destruction are modulated by recombinant osteoprotegerin. Immunity 19: 849-861, 2003.
10. Atkins GJ, Welldon KJ, Wijenayaka AR, Bonewald LF, Findlay DM. Vitamin K promotes mineralization, osteoblast-to-osteocyte transition, and an anticatabolic phenotype by γ-carboxylation-dependent and - independent mechanisms. Am J Physiol Cell Physiol 297: C1358-C1367, 2009.
11. Benchimol EI, Ward LM, Gallagher JC, Rauch F, Barrowman N, Warren J, Beedle S, Mack DR. Effect of calcium and vitamin D supplementation on bone mineral density in children with inflammatory bowel disease. J Pediatr Gastroenterol Nutr 45: 538-545, 2007.
12. Bernstein CN, Sargent M, Leslie WD. Serum osteoprotegerin is increased in Crohn's disease: a population-based case control study. Inflamm Bowel Dis 11: 325-330, 2005.
13. Bernstein CN, Seeger LL, Anton PA, Artinian L, Geffrey S, Goodman W, Belin TR, Shanahan F. A randomized, placebo-controlled trial of calcium supplementation for decreased bone density in corticosteroidusing patients with inflammatory bowel disease: a pilot study. Aliment Pharmacol Ther 10: 777-786, 1996.
14. Bianco SD, Peng JB, Takanaga H, Suzuki Y, Crescenzi A, Kos CH, Zhuang L, Freeman MR, Gouveia CH, Wu J, Luo H, Mauro T, Brown EM, Hediger MA. Marked disturbance of calcium homeostasis in mice with targeted disruption of the Trpv6 calcium channel gene. J Bone Miner Res 22: 274-285, 2007.
15. 2+ transport across primary cultures of rabbit kidney collecting system. Pflügers Arch 420: 566-572, 1992.
16. Binkley N. Is vitamin D the fountain of youth? Endocr Pract 15: 590-596, 2009.
17. Bischoff SC, Herrmann A, Goke M, Manns MP, von zur Muhlen A, Brabant G. Altered bone metabolism in inflammatory bowel disease. Am J Gastroenterol 92: 1157-1163, 1997.
18. Bjarnason I, Macpherson A, Mackintosh C, Buxton-Thomas M, Forgacs I, Moniz C. Reduced bone density in patients with inflammatory bowel disease. Gut 40: 228-233, 1997.
19. Bronner F. Recent developments in intestinal calcium absorption. Nutr Rev 67: 109-113, 2009.
20. Byrne FR, Morony S, Warmington K, Geng Z, Brown HL, Flores SA, Fiorino M, Yin SL, Hill D, Porkess V, Duryea D, Pretorius JK, Adamu S, Manoukian R, Danilenko DM, Sarosi I, Lacey DL, Kostenuik PJ, Senaldi G. CD4+CD45RBHi T cell transfer induced colitis in mice is accompanied by osteopenia which is treatable with recombinant human osteoprotegerin. Gut 54: 78-86, 2005.
21. Chang J, Wang Z, Tang E, Fan Z, McCauley L, Franceschi R, Guan K, Krebsbach PH, Wang CY. Inhibition of osteoblastic bone formation by nuclear factor-kappaB. Nat Med 15: 682-689, 2009.
22. Chen H, Xu H, Dong J, Li J, Ghishan FK. Tumor necrosis factor-α impairs intestinal phosphate absorption in colitis. Am J Physiol Gastrointest Liver Physiol 296: G775-G781, 2009.
23. Christakos S, Ajibade DV, Dhawan P, Fechner AJ, Mady LJ. Vitamin D: metabolism. Endocrinol Metab Clin North Am 39: 243-253, 2010.
24. Civitelli R, Armamento-Villareal R, Napoli N. Bone turnover markers: understanding their value in clinical trials and clinical practice. Osteoporos Int 20: 843-851, 2009.
25. Collins JF, Bai L, Ghishan FK. The SLC20 family of proteins: dual functions as sodium-phosphate cotransporters and viral receptors. Pflügers Arch 447: 647-652, 2004.
26. Corut A, Senyigit A, Ugur SA, Altin S, Ozcelik U, Calisir H, Yildirim Z, Gocmen A, Tolun A. Mutations in SLC34A2 cause pulmonary alveolar microlithiasis and are possibly associated with testicular microlithiasis. Am J Hum Genet 79: 650-656, 2006.
27. Coutu DL, Wu JH, Monette A, Rivard GE, Blostein MD, Galipeau J. Periostin, a member of a novel family of vitamin K-dependent proteins, is expressed by mesenchymal stromal cells. J Biol Chem 283: 17991-18001, 2008.
28. Cranenburg EC, Schurgers LJ, Vermeer C. Vitamin K: the coagulation vitamin that became omnipotent. Thromb Haemost 98: 120-125, 2007.
29. De Groot T, Bindels RJ, Hoenderop JG. TRPV5: an ingeniously controlled calcium channel. Kidney Int 74: 1241-1246, 2008.
30. Di Stefano M, Veneto G, Malservisi S, Cecchetti L, Minguzzi L, Strocchi A, Corazza GR. Lactose malabsorption and intolerance and peak bone mass. Gastroenterology 122: 1793-1799, 2002.
31. Dresner-Pollak R, Gelb N, Rachmilewitz D, Karmeli F, Weinreb M. Interleukin 10-deficient mice develop osteopenia, decreased bone formation, and mechanical fragility of long bones. Gastroenterology 127: 792-801, 2004.
32. Duggan P, O'Brien M, Kiely M, McCarthy J, Shanahan F, Cashman KD. Vitamin K status in patients with Crohn's disease and relationship to bone turnover. Am J Gastroenterol 99: 2178-2185, 2004.
33. El-Matary W, Sikora S, Spady D. Bone mineral density, vitamin D, and disease activity in children newly diagnosed with inflammatory bowel disease. Dig Dis Sci 2010. Aug 20. [Epub ahead of print].
34. Eto N, Tomita M, Hayashi M. NaPi-mediated transcellular permeation is the dominant route in intestinal inorganic phosphate absorption in rats. Drug Metab Pharmacokinet 21: 217-221, 2006.
35. Fries W, Giacomin D, Plebani M, Martin A. Effect of experimental colitis on bone metabolism in the rat. Digestion 55: 229-233, 1994. (Pubitemid 24168025)
36. Fugate SE, Ramsey AM. Resistance to oral vitamin K for reversal of overanticoagulation during Crohn's disease relapse. J Thromb Thrombolysis 17: 219-223, 2004.
37. Gattineni J, Bates C, Twombley K, Dwarakanath V, Robinson ML, Goetz R, Mohammadi M, Baum M. FGF23 decreases renal NaPi-2a and NaPi-2c expression and induces hypophosphatemia in vivo predominantly via FGF receptor 1. Am J Physiol Renal Physiol 297: F282-F291, 2009.
38. Gilman J, Shanahan F, Cashman KD. Altered levels of biochemical indices of bone turnover and bone-related vitamins in patients with Crohn's disease and ulcerative colitis. Aliment Pharmacol Ther 23: 1007-1016, 2006.
39. Giral H, Caldas Y, Sutherland E, Wilson P, Breusegem S, Barry N, Blaine J, Jiang T, Wang XX, Levi M. Regulation of rat intestinal Na-dependent phosphate transporters by dietary phosphate. Am J Physiol Renal Physiol 297: F1466-F1475, 2009.
40. Hamdani G, Gabet Y, Rachmilewitz D, Karmeli F, Bab I, Dresner-Pollak R. Dextran sodium sulfate-induced colitis causes rapid bone loss in mice. Bone 43: 945-950, 2008.
41. Harris L, Senagore P, Young VB, McCabe LR. Inflammatory bowel disease causes reversible suppression of osteoblast and chondrocyte function in mice. Am J Physiol Gastrointest Liver Physiol 296: G1020-G1029, 2009.
42. Hewison M. Vitamin D and the immune system: new perspectives on an old theme. Endocrinol Metab Clin North Am 39: 365-379, 2010.
43. Hill RJ, Brookes DS, Davies PS. Bones in pediatric Crohn's disease: a review of fracture risk in children and adults. Inflamm Bowel Dis 2010. Sep 7. [Epub ahead of print].
44. Hoenderop JG, Nilius B, Bindels RJ. Calcium absorption across epithelia. Physiol Rev 85: 373-422, 2005.
45. Hu MC, Shi M, Zhang J, Pastor J, Nakatani T, Lanske B, Razzaque MS, Rosenblatt KP, Baum MG, Kuro-o M, Moe OW. Klotho: a novel phosphaturic substance acting as an autocrine enzyme in the renal proximal tubule. FASEB J 24: 3438-3450, 2010.
46. 2+ transporters. Inflamm Bowel Dis 14: 803-811, 2008.
47. 2+ channel TRPV6. Am J Physiol Gastrointest Liver Physiol 292: G92-G97, 2007.
48. 2-activated transcription of extracellular matrix-related genes and collagen accumulation in osteoblastic cells. J Biol Chem 281: 16927-16934, 2006.
49. Kanis JA, Melton LJ 3rd, Christiansen C, Johnston CC, Khaltaev N. The diagnosis of osteoporosis. J Bone Miner Res 9: 1137-1141, 1994.
50. Khanal RC, Nemere I. Regulation of intestinal calcium transport. Annu Rev Nutr 28: 179-196, 2008.
51. Kiela PR, Ghishan FK. Recent advances in the renal-skeletal-gut axis that controls phosphate homeostasis. Lab Invest 89: 7-14, 2009.
52. Kirkland JB. Poly ADP-ribose polymerase-1 and health. Exp Biol Med (Maywood) 235: 561-568, 2010.
53. 3 upregulates FGF23 gene expression in bone: the final link in a renalgastrointestinal- skeletal axis that controls phosphate transport. Am J Physiol Gastrointest Liver Physiol 289: G1036-G1042, 2005.
54. Koushik SV, Wang J, Rogers R, Moskophidis D, Lambert NA, Creazzo TL, Conway SJ. Targeted inactivation of the sodium-calcium exchanger (Ncx1) results in the lack of a heartbeat and abnormal myofibrillar organization. FASEB J 15: 1209-1211, 2001.
55. Kumari M, Khazai NB, Ziegler TR, Nanes MS, Abrams SA, Tangpricha V. Vitamin D-mediated calcium absorption in patients with clinically stable Crohn's disease: A pilot study. Mol Nutr Food Res 54: 1085-1091, 2010.
56. Kuro-o M, Matsumura Y, Aizawa H, Kawaguchi H, Suga T, Utsugi T, Ohyama Y, Kurabayashi M, Kaname T, Kume E, Iwasaki H, Iida A, Shiraki-Iida T, Nishikawa S, Nagai R, Nabeshima YI. Mutation of the mouse klotho gene leads to a syndrome resembling ageing. Nature 390: 45-51, 1997.
57. Kutuzova GD, Akhter S, Christakos S, Vanhooke J, Kimmel-Jehan C, Deluca HF. Calbindin D (9k) knockout mice are indistinguishable from wild-type mice in phenotype and serum calcium level. Proc Natl Acad Sci USA 103: 12377-12381, 2006.
58. Kuwabara A, Tanaka K, Tsugawa N, Nakase H, Tsuji H, Shide K, Kamao M, Chiba T, Inagaki N, Okano T, Kido S. High prevalence of vitamin K and D deficiency and decreased BMD in inflammatory bowel disease. Osteoporos Int 20: 935-942, 2009.
59. Larsen S, Bendtzen K, Nielsen OH. Extraintestinal manifestations of inflammatory bowel disease: epidemiology, diagnosis, and management. Ann Med 42: 97-114, 2010.
60. Leslie WD, Miller N, Rogala L, Bernstein CN. Vitamin D status and bone density in recently diagnosed inflammatory bowel disease: the Manitoba IBD Cohort Study. Am J Gastroenterol 103: 1451-1459, 2008.
61. Lichtenstein GR, Sands BE, Pazianas M. Prevention and treatment of osteoporosis in inflammatory bowel disease. Inflamm Bowel Dis 12: 797-813, 2006.
62. 2+ channels TRPV5 and TRPV6. Nephrol Dial Transplant 23: 3397-3402, 2008.
63. Majewski PM, Thurston RD, Ramalingam R, Kiela PR, Ghishan FK. Cooperative role of NF-κB and poly (ADP-ribose) polymerase 1 (PARP-1) in the TNF-induced inhibition of PHEX expression in osteoblasts. J Biol Chem 285: 34828-34838, 2010.
64. Margolis DS, Kim D, Szivek JA, Lai LW, Lien YH. Functionally improved bone in calbindin-D28k knockout mice. Bone 39: 477-484, 2006.
65. Marks J, Debnam ES, Unwin RJ. Phosphate homeostasis and the renal-gastrointestinal axis. Am J Physiol Renal Physiol 299: F285-F296, 2010.
66. Martin A, Fries W, Luisetto G, Mussolin L, Plebani M, Giacomin D, Naccarato R. Bone-density and calcium-metabolism in patients with long-standing, quiescent Crohns-disease. Eur J Gastroenterol Hepatol 6: 611-616, 1994.
67. Mascarenhas MR, Thayu M. Pediatric inflammatory bowel disease and bone health. Nutr Clin Pract 25: 347-352, 2010.
68. Miheller P, Muzes G, Racz K, Blazovits A, Lakatos P, Herszenyi L, Tulassay Z. Changes of OPG and RANKL concentrations in Crohn's disease after infliximab therapy. Inflamm Bowel Dis 13: 1379-1384, 2007. (Pubitemid 350206849)
69. Miheller P, Toth M, Molnar E, Zagoni T, Racz K, Tulassay Z. [Serum bone marker measurements in bone metabolism disorders associated with inflammatory bowel diseases]. Orv Hetil 142: 1557-1560, 2001.
70. Moe SM. Disorders involving calcium, phosphorus, and magnesium. Prim Care 35: 215-237, v-vi, 2008.
71. Moschen AR, Kaser A, Enrich B, Ludwiczek O, Gabriel M, Obrist P, Wolf AM, Tilg H. The RANKL/OPG system is activated in inflammatory bowel disease and relates to the state of bone loss. Gut 54: 479-487, 2005.
72. Nakashima T, Takayanagi H. Osteoimmunology: crosstalk between the immune and bone systems. J Clin Immunol 29: 555-567, 2009.
73. Ohnishi M, Nakatani T, Lanske B, Razzaque MS. Reversal of mineral ion homeostasis and soft-tissue calcification of klotho knockout mice by deletion of vitamin D 1alpha-hydroxylase. Kidney Int 75: 1166-1172, 2009.
74. 2+-ATPase (PMCA) 1 and 4 indicates a major housekeeping function for PMCA1 and a critical role in hyperactivated sperm motility and male fertility for PMCA4. J Biol Chem 279: 33742-33750, 2004.
75. Papet I, El Yousfi M, Godin JP, Mermoud AF, Davicco MJ, Coxam V, Breuille D, Obled C. HLA-B27 rats develop osteopaenia through increased bone resorption without any change in bone formation. J Musculoskelet Neuronal Interact 8: 251-256, 2008.
76. Poser JW, Esch FS, Ling NC, Price PA. Isolation and sequence of the vitamin K-dependent protein from human bone. Undercarboxylation of the first glutamic acid residue. J Biol Chem 255: 8685-8691, 1980.
77. Price PA, Williamson MK. Primary structure of bovine matrix Gla protein, a new vitamin K-dependent bone protein. J Biol Chem 260: 14971-14975, 1985.
78. Raggatt LJ, Partridge NC. Cellular and molecular mechanisms of bone remodeling. J Biol Chem 285: 25103-25108, 2010.
79. Rauner M, Stupphann D, Haas M, Fert I, Glatigny S, Sipos W, Breban M, Pietschmann P. The HLA-B27 transgenic rat, a model of spondyloarthritis, has decreased bone mineral density and increased RANKL to osteoprotegerin mRNA ratio. J Rheumatol 36: 120-126, 2009.
80. Renkema KY, Alexander RT, Bindels RJ, Hoenderop JG. Calcium and phosphate homeostasis: concerted interplay of new regulators. Ann Med 40: 82-91, 2008.
81. 2+ hyperabsorption in TRPV5 knockout mice. J Am Soc Nephrol 16: 3188-3195, 2005.
82. Riancho JA, Valero C, Hernandez JL, Ortiz F, Zarrabeitia A, Alonso MA, Pena N, Pascual MA, Gonzalez-Macias J, Zarrabeitia MT. Association of the F352V variant of the Klotho gene with bone mineral density. Biogerontology 8: 121-127, 2007.
83. Robinson RJ, Iqbal SJ, Abrams K, Al-Azzawi F, Mayberry JF. Increased bone resorption in patients with Crohn's disease. Aliment Pharmacol Ther 12: 699-705, 1998. (Pubitemid 28369874)
84. Romas E. Clinical applications of RANK-ligand inhibition. Intern Med J 39: 110-116, 2009.
85. Rouleau M, Patel A, Hendzel MJ, Kaufmann SH, Poirier GG. PARP inhibition: PARP1 and beyond. Nat Rev Cancer 10: 293-301, 2010.
86. Rudnicki M, Frolich A, Transbol I. Inappropriate hypercalcitriolemia in ileum-resected patients with Crohn's disease. Miner Electrolyte Metab 18: 52-55, 1992.
87. Sabbagh Y, O'Brien SP, Song W, Boulanger JH, Stockmann A, Arbeeny C, Schiavi SC. Intestinal npt2b plays a major role in phosphate absorption and homeostasis. J Am Soc Nephrol 20: 2348-2358, 2009.
88. Schoeber JP, Hoenderop JG, Bindels RJ. Concerted action of associated proteins in the regulation of TRPV5 and TRPV6. Biochem Soc Trans 35: 115-119, 2007. (Pubitemid 46271823)
89. Schoon EJ, Geerling BG, Van Dooren IM, Schurgers LJ, Vermeer C, Brummer RJ, Stockbrugger RW. Abnormal bone turnover in longstanding Crohn's disease in remission. Aliment Pharmacol Ther 15: 783-792, 2001. (Pubitemid 32500424)
90. Schoon EJ, Muller MC, Vermeer C, Schurgers LJ, Brummer RJ, Stockbrugger RW. Low serum and bone vitamin K status in patients with longstanding Crohn's disease: another pathogenetic factor of osteoporosis in Crohn's disease? Gut 48: 473-477, 2001.
91. Schulte C, Dignass AU, Mann K, Goebell H. Reduced bone mineral density and unbalanced bone metabolism in patients with inflammatory bowel disease. Inflamm Bowel Dis 4: 268-275, 1998.
92. Shikhare G, Kugathasan S. Inflammatory bowel disease in children: current trends. J Gastroenterol 45: 673-682, 2010.
93. Silvennoinen J, Risteli L, Karttunen T, Risteli J. Increased degradation of type I collagen in patients with inflammatory bowel disease. Gut 38: 223-228, 1996. (Pubitemid 26048699)
94. St-Arnaud R, Arabian A, Travers R, Barletta F, Raval-Pandya M, Chapin K, Depovere J, Mathieu C, Christakos S, Demay MB, Glorieux FH. Deficient mineralization of intramembranous bone in vitamin D-24-hydroxylase-ablated mice is due to elevated 1,25-dihydroxyvitamin D and not to the absence of 24,25-dihydroxyvitamin D. Endocrinology 141: 2658-2666, 2000.
95. 2+ absorption in health and disease. Annu Rev Physiol 70: 257-271, 2008.
96. Sylvester FA. IBD and skeletal health: children are not small adults! Inflamm Bowel Dis 11: 1020-1023, 2005.
97. Sylvester FA, Wyzga N, Hyams JS, Davis PM, Lerer T, Vance K, Hawker G, Griffiths AM. Natural history of bone metabolism and bone mineral density in children with inflammatory bowel disease. Inflamm Bowel Dis 13: 42-50, 2007.
98. 2 regulation of bone homeostasis is mediated by the steroid and xenobiotic receptor SXR. J Biol Chem 278: 43919-43927, 2003.
99. Takeuchi Y, Suzawa M, Fukumoto S, Fujita T. Vitamin K(2) inhibits adipogenesis, osteoclastogenesis, and ODF/RANK ligand expression in murine bone marrow cell cultures. Bone 27: 769-776, 2000.
100. Thurston RD, Larmonier CB, Majewski PM, Ramalingam R, Midura-Kiela M, Laubitz D, Vandewalle A, Besselsen DG, Muhlbauer M, Jobin C, Kiela PR, Ghishan FK. Tumor necrosis factor and interferon-gamma down-regulate Klotho in mice with colitis. Gastroenterology 138: 1384-1394, 1394.e1-2, 2010.
101. Tuchman S, Thayu M, Shults J, Zemel BS, Burnham JM, Leonard MB. Interpretation of biomarkers of bone metabolism in children: impact of growth velocity and body size in healthy children and chronic disease. J Pediatr 153: 484-490, 2008.
102. Turk N, Cukovic-Cavka S, Korsic M, Turk Z, Vucelic B. Proinflammatory cytokines and receptor activator of nuclear factor kappaB-ligand/osteoprotegerin associated with bone deterioration in patients with Crohn's disease. Eur J Gastroenterol Hepatol 21: 159-166, 2009.
103. Uno JK, Kolek OI, Hines ER, Xu H, Timmermann BN, Kiela PR, Ghishan FK. The role of tumor necrosis factor alpha in down-regulation of osteoblast Phex gene expression in experimental murine colitis. Gastroenterology 131: 497-509, 2006.
104. Urakawa I, Yamazaki Y, Shimada T, Iijima K, Hasegawa H, Okawa K, Fujita T, Fukumoto S, Yamashita T. Klotho converts canonical FGF receptor into a specific receptor for FGF23. Nature 444: 770-774, 2006.
105. i. Am J Physiol Renal Physiol 296: F691-F699, 2009.
106. 106a vitamin K2. Monograph. Altern Med Rev 14: 284-293, 2009.
107. Ward LM, Rauch F, Matzinger MA, Benchimol EI, Boland M, Mack DR. Iliac bone histomorphometry in children with newly diagnosed inflammatory bowel disease. Osteoporos Int 21: 331-337, 2010.
108. Williams KB, DeLuca HF. Characterization of intestinal phosphate absorption using a novel in vivo method. Am J Physiol Endocrinol Metab 292: E1917-E1921, 2007.
109. Xiao ZS, Crenshaw M, Guo R, Nesbitt T, Drezner MK, Quarles LD. Intrinsic mineralization defect in Hyp mouse osteoblasts. Am J Physiol Endocrinol Metab 275: E700-E708, 1998.
110. Zarrabeitia MT, Hernandez JL, Valero C, Zarrabeitia AL, Ortiz F, Gonzalez-Macias J, Riancho JA. Klotho gene polymorphism and male bone mass. Calcif Tissue Int 80: 10-14, 2007.