Are vitamin D receptor activators useful for the treatment of thrombosis?

Current Opinion in Investigational Drugs

Volumn 10, Issue 9, 2009, Pages 919-927

  Wu Wong, J R ^a  

^a UNIVERSITY OF ILLINOIS AT CHICAGO   (United States)

Author keywords

Calcitriol; Paricalcitol; Thrombosis; Vitamin D; Vitamin D deficiency; Vitamin D receptor; Vitamin D receptor activator

Indexed keywords

ANTINEOPLASTIC AGENT; ANTITHROMBOCYTIC AGENT; C REACTIVE PROTEIN; CALCITRIOL; COLECALCIFEROL; DOCETAXEL; ERGOCALCIFEROL; HEMOSTATIC AGENT; HEPARIN; LOW MOLECULAR WEIGHT HEPARIN; PARICALCITOL; THROMBOMODULIN; UNCLASSIFIED DRUG; VITAMIN D; VITAMIN D DERIVATIVE; VITAMIN D RECEPTOR; VITAMIN D RECEPTOR ACTIVATOR; WARFARIN;

ANGIOGENESIS; ANTIINFLAMMATORY ACTIVITY; ATHEROSCLEROSIS; BREAST CANCER; CANCER CHEMOTHERAPY; CANCER SURGERY; CARCINOGENESIS; CARDIOVASCULAR DISEASE; CHRONIC KIDNEY DISEASE; CLINICAL ASSESSMENT; CLINICAL TRIAL; COLON CANCER; CORONARY ARTERY ATHEROSCLEROSIS; DIAGNOSTIC TEST; DISEASE ASSOCIATION; DISEASE SEVERITY; DRUG BINDING; DRUG BLOOD LEVEL; DRUG EFFICACY; DRUG MECHANISM; DRUG MEGADOSE; DRUG OVERDOSE; GENE EXPRESSION; HEART INFARCTION; HEMOSTASIS; HUMAN; HYPERPARATHYROIDISM; HYPERTENSION; INFLAMMATION; KIDNEY ALLOGRAFT; LOW DRUG DOSE; NEOPLASM; NONHUMAN; PATHOPHYSIOLOGY; PERIPHERAL VASCULAR DISEASE; PHENOTYPE; PROSPECTIVE STUDY; PROSTATE CANCER; RECEPTOR UPREGULATION; REVIEW; RISK FACTOR; RISK REDUCTION; STROKE; THROMBOGENICITY; THROMBOSIS; TUMOR THROMBUS; VENOUS THROMBOEMBOLISM; VITAMIN SUPPLEMENTATION;

ANIMALS; CALCITRIOL; CLINICAL TRIALS AS TOPIC; HUMANS; MICE; MODELS, BIOLOGICAL; MOLECULAR STRUCTURE; RECEPTORS, CALCITRIOL; THROMBOSIS;

EID: 69549118747     PISSN: 14724472     EISSN: None     Source Type: Journal    
DOI: None     Document Type: Review

References (86)

1. Cesarman-Maus G, Hajjar KA: 1. Molecular mechanisms of fibrinolysis. Br J Haematol (2005) 129(3):307-321.
2. Gailani D, Renné T: Intrinsic pathway of coagulation and arterial thrombosis. Arterioscler Thromb Vasc Biol (2007) 27(12):2507-2513. (Pubitemid 350158899)
3. Poredos P, Jezovnik MK: The role of inflammation in venous thromboembolism and the link between arterial and venous thrombosis. Int Angiol (2007) 26(4):306-311. (Pubitemid 351227733)
4. Andress DL: Vitamin D in chronic kidney disease: A systemic role for selective vitamin D receptor activation. Kidney Int (2006) 69(1):33-43.
5. Wu-Wong JR, Tian J, Nakane M, Ma J, Fey TA, Kroeger P, Fryer RM, Reinhart GA: Cardiovascular disease in chronic kidney failure: The role of VDR activators. Curr Opin Investig Drugs (2006) 7(3):206-213.
6. Brown AJ, Slatopolsky E: Drug insight: Vitamin D analogs in the treatment of secondary hyperparathyroidism in patients with chronic kidney disease. Nat Clin Pract Endocrinol Metab (2007) 3(2):134-144. (Pubitemid 46146966)
7. Cheskis BJ, Freedman LP, Nagpal S: Vitamin D receptor ligands for osteoporosis. Curr Opin Investig Drugs (2006) 7(10):906-911.
8. Fogh K, Kragballe K: New vitamin D analogs in psoriasis. Curr Drug Targets Inflamm Allergy (2004) 3(2):199-204.
9. Nagpal S, Na S, Rathnachalam R: Noncalcemic actions of vitamin D receptor ligands. Endocr Rev (2005) 26(5):662-687. (Pubitemid 41127276)
10. Martins D, Wolf M, Pan D, Zadshir A, Tareen N, Thadhani R, Felsenfeld A, Levine B, Mehrotra R, Norris K: Prevalence of cardiovascular risk factors and the serum levels of 25-hydroxyvitamin D in the United States: Data from the Third National Health and Nutrition Examination Survey. Arch Intern Med (2007) 167(11):1159-1165. (Pubitemid 46919818)
11. Dobnig H, Pilz S, Scharnagl H, Renner W, Seelhorst U, Wellnitz B, Kinkeldei J, Boehm BO, Weihrauch G, Maerz W: Independent association of low serum 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D levels with all-cause and cardiovascular mortality. Arch Intern Med (2008) 168(12):1340-1349. (Pubitemid 351930842)
12. Giovannucci E, Liu Y, Hollis BW, Rimm EB: 25-Hydroxyvitamin D and risk of myocardial infarction in men: A prospective study. Arch Intern Med (2008) 168(11):1174-1180. (Pubitemid 351831400)
13. Wang TJ, Pencina MJ, Booth SL, Jacques PF, Ingelsson E, Lanier K, Benjamin EJ, D'Agostino RB, Wolf M, Vasan RS: Vitamin D deficiency and risk of cardiovascular disease. Circulation (2008) 117(4): 503-511.
14. Melamed ML, Michos ED, Post W, Astor B: 25-Hydroxyvitamin D levels and the risk of mortality in the general population. Arch Intern Med (2008) 168(15):1629-1637.
15. Teng M, Wolf M, Lowrie E, Ofsthun N, Lazarus JM, Thadhani R: Survival of patients undergoing hemodialysis with paricalcitol or calcitriol therapy. N Engl J Med (2003) 349(5):446-456. • Presents data from retrospective clinical trials demonstrating that the survival benefit of paricalcitol was greater than that of calcitriol in patients undergoing hemodialysis. (Pubitemid 36910023)
16. 3 users in a haemodialysis population. Nephrol Dial Transplant (2004) 19(1):179-184.
17. Teng M, Wolf M, Ofsthun MN, Lazarus JM, Hernán MA, Camargo CA Jr, Thadhani R: Activated injectable vitamin D and hemodialysis survival: A historical cohort study. J Am Soc Nephrol (2005) 16(4):1115-1125. •• Presents data from retrospective clinical trials demonstrating that VDR therapy produced an increased survival benefit in patients undergoing hemodialysis. (Pubitemid 41710323)
18. Melamed ML, Eustace JA, Plantinga L, Jaar BG, Fink NE, Coresh J, Klag MJ, Powe NR: Changes in serum calcium, phosphate, and PTH and the risk of death in incident dialysis patients: A longitudinal study. Kidney Int (2006) 70(2):351-357. (Pubitemid 44086585)
19. Kalantar-Zadeh K, Kuwae N, Regidor DL, Kovesdy CP, Kilpatrick RD, Shinaberger CS, McAllister CJ, Budoff MJ, Salusky IB, Kopple JD: Survival predictability of time-varying indicators of bone disease in maintenance hemodialysis patients. Kidney Int (2006) 70(4):771-780. •• Presents data from a 2-year study investigating associations between survival and quarterly laboratory values in patients from all DaVita dialysis clinics in the US (n = 58,058) who were undergoing maintenance hemodialysis and receiving paricalcitol at 1 to 15 μg weekly. Both time-dependent Cox models with repeated measures and fixed-covariate Cox models with only baseline values were used to assess the data. The results indicated that the administration of paricalcitol at all doses was associated with improved survival in time-varying models. (Pubitemid 44215354)
20. Lee GH, Benner D, Regidor DL, Kalantar-Zadeh K: Impact of kidney bone disease and its management on survival of patients on dialysis. J Ren Nutr (2007) 17(1):38-44. (Pubitemid 46014446)
21. Tentori F, Hunt WC, Stidley CA, Rohrscheib MR, Bedrick EJ, Meyer KB, Johnson HK, Zager PG: Mortality risk among hemodialysis patients receiving different vitamin D analogs. Kidney Int (2006) 70(10):1858-1865. (Pubitemid 44684819)
22. Wolf M, Shah A, Gutierrez O, Ankers E, Monroy M, Tamez H, Steele D, Chang Y, Camargo CA Jr, Tonelli M, Thadhani R: Vitamin D levels and early mortality among incident hemodialysis patients. Kidney Int (2007) 72(8):1004-1013. (Pubitemid 47530570)
23. Wolf M, Betancourt J, Chang Y, Shah A, Teng M, Tamez H, Gutierrez O, Camargo CA Jr, Melamed M, Norris K, Stampfer MJ et al: Impact of activated vitamin D and race on survival among hemodialysis patients. J Am Soc Nephrol (2008) 19(7):1379-1388. • Presents data from a prospective cohort study in non-Hispanic white, Hispanic white and African-American patients undergoing incident hemodialysis. The data demonstrated that African-American patients exhibited 16% lower mortality compared with white patients when treated with vitamin D activators; however, this difference was not present when the data were adjusted for vitamin D dosing. In contrast, African- American patients who were not treated with activated vitamin D had 35% higher mortality compared with untreated white patients. It was proposed that the survival advantage observed may have resulted from vitamin D therapy because PTH levels are usually higher among healthy African-American individuals, as well as African-American patients with kidney disease; consequently, this population was most likely to receive a higher dose of vitamin D.
24. Shinaberger CS, Kopple JD, Kovesdy CP, McAllister CJ, van Wyck D, Greenland S, Kalantar-Zadeh K: Ratio of paricalcitol dosage to serum parathyroid hormone level and survival in maintenance hemodialysis patients. Clin J Am Soc Nephrol (2008) 3(6): 1769-1776.
25. Naves-Díaz M, Alvarez-Hernández D, Passlick-Deetjen J, Guinsburg A, Marelli C, Rodriguez-Puyol D, Cannata-Andía JB: Oral active vitamin D is associated with improved survival in hemodialysis patients. Kidney Int (2008) 74(8):1070-1078.
26. Shoben AB, Rudser KD, de Boer IH, Young B, Kestenbaum B: Association of oral calcitriol with improved survival in nondialyzed CKD. J Am Soc Nephrol (2008) 19(8):1613-1619.
27. Kovesdy CP, Ahmadzadeh S, Anderson JE, Kalantar-Zadeh K: Association of activated vitamin D treatment and mortality in chronic kidney disease. Arch Intern Med (2008) 168(4):397-403. (Pubitemid 351350586)
28. Levin A, Djurdjev O, Beaulieu M, Er L: Variability and risk factors for kidney disease progression and death following attainment of stage 4 CKD in a referred cohort. Am J Kidney Dis (2008) 52(4):661-671.
29. Kovesdy CP, Kalantar-Zadeh K: Vitamin D receptor activation and survival in chronic kidney disease. Kidney Int (2008) 73(12):1355-1363. (Pubitemid 351770491)
30. Wu-Wong JR: Potential for vitamin D receptor agonists in the treatment of cardiovascular disease. Br J Pharmacol (2009): doi: 10.1111/j1476-5381.2009. 00171.x.
31. 3 is a negative endocrine regulator of the renin-angiotensin system. J Clin Invest (2002) 110(2):229-238. • One of the first studies to demonstrate that the VDR is involved in the modulation of cardiovascular function.
32. Aihara K, Azuma H, Akaike M, Ikeda Y, Yamashita M, Sudo T, Hayashi H, Yamada Y, Endoh F, Fujimura M, Yoshida T et al: Disruption of nuclear vitamin D receptor gene causes enhanced thrombogenicity in mice. J Biol Chem (2004) 279(34):35798-35802. • Presents data demonstrating that VDR-/- mice exhibited multi-organ thrombus formation following LPS injection. Platelet aggregation was enhanced significantly in VDR-/- mice fed a normal diet (1.2% calcium) compared with wild-type mice. Increasing the calcium content to 2% in the diet corrected the hypocalcemic phenotype, as well as the abnormality in platelet aggregation. However, the gene expression of antithrombin in the plasma and liver, and thrombomodulin in the aorta, liver and kidney of VDR-/- mice was downregulated independent of the plasma calcium level. (Pubitemid 39100586)
33. Korte W: Cancer and thrombosis: An increasingly important association. Support Care Cancer (2008) 16(3):223-228.
34. Froicu M, Weaver V, Wynn TA, McDowell MA, Welsh JE, Cantorna MT: A crucial role for the vitamin D receptor in experimental inflammatory bowel diseases. Mol Endocrinol (2003) 17(12):2386-2392. (Pubitemid 37542204)
35. -/- mice.
36. 3 receptor ablation sensitizes skin to chemically induced tumorigenesis. Carcinogenesis (2002) 23(12):2103-2109.
37. Fukumoto S, Allan EH, Martin TJ: 37. Regulation of plasminogen activator inhibitor-1 (PAI-1) expression by 1,25-dihydroxyvitamin D-3 in normal and malignant rat osteoblasts. Biochim Biophys Acta (1994) 1201(2):223-228. (Pubitemid 24349907)
38. 3 on human myelogenous leukemia cells and monocytes. Blood (1998) 92(1):160-167.
39. Puri S, Bansal DD, Uskoković MR, MacGregor RR: Induction of tissue plasminogen activator secretion from rat heart microvascular cells by fM 1,25(OH)2D3. Am J Physiol Endocrinol Metab (2000) 278(2):E293-E301. (Pubitemid 30131177)
40. 3 modulation of plasminogen activator inhibitor type-1 in human breast carcinomas under organ culture. Virchows Arch (2004) 444(2):175-182.
41. Wu-Wong JR, Nakane M, Ma J: Vitamin D analogs modulate the expression of plasminogen activator inhibitor-1, thrombospondin-1 and thrombomodulin in human aortic smooth muscle cells. J Vasc Res (2007) 44(1):11-18. (Pubitemid 46105689)
42. Wu-Wong JR, Nakane M, Ma J, Ruan X, Kroeger PE: VDR-mediated gene expression patterns in resting human coronary artery smooth muscle cells. J Cell Biochem (2007) 100(6):1395-1405. (Pubitemid 46515574)
43. Nordt TK, Peter K, Ruef J, Kübler W, Bode C: Plasminogen activator inhibitor type-1 (PAI-1) and its role in cardiovascular disease. Thromb Haemost (1999) 82(Suppl 1):14-18. (Pubitemid 30093624)
44. Esmon CT: Protein C anticoagulant pathway and its role in controlling microvascular thrombosis and inflammation. Crit Care Med (2001) 29(7 Suppl 1):S48-S51.
45. Sid B, Sartelet H, Bellon G, El Btaouri H, Rath G, Delorme N, Haye B, Martiny L: Thrombospondin 1: A multifunctional protein implicated in the regulation of tumor growth. Crit Rev Oncol Hematol (2004) 49(3):245-258. (Pubitemid 38251356)
46. Lupu F, Bergonzelli GE, Heim DA, Cousin E, Genton CY, Bachmann F, Kruithof EK: Localization and production of plasminogen activator inhibitor-1 in human healthy and atherosclerotic arteries. Arterioscler Thromb (1993) 13(7):1090-1100. (Pubitemid 23195812)
47. Salame MY, Samani NJ, Masood I, deBono DP: Expression of the plasminogen activator system in the human vascular wall. Atherosclerosis (2000) 152(1):19-28.
48. Schafer K, Muller K, Hecke A, Mounier E, Goebel J, Loskutoff DJ, Konstantinides S: Enhanced thrombosis in atherosclerosisprone mice is associated with increased arterial expression of plasminogen activator inhibitor-1. Arterioscler Thromb Vasc Biol (2003) 23(11):2097-2103. (Pubitemid 37433206)
49. Petrie MS, Harrell TE, Schwartz GG, Sane DC: Production of plasminogen activator inhibitor-1 (PAI-1) by endothelial cells: Differential responses to calcitriol and paricalcitol. J Thromb Haemost (2004) 2(12):2266-2267.
50. 3 and calcipotriol decrease extracellular plasminogen activator activity in cultured keratinocytes. J Invest Dermatol (1993) 101(5):706-712.
51. Jorde R, Haug E, Figenschau Y, Hansen JB: Serum levels of vitamin D and haemostatic factors in healthy subjects: The Tromso study. Acta Haematol (2007) 117(2):91-97. (Pubitemid 46272248)
52. Yee YK, Chintalacharuvu SR, Lu J, Nagpal S: Vitamin D receptor modulators for inflammation and cancer. Mini Rev Med Chem (2005) 5(8):761-778. (Pubitemid 41051899)
53. 3 and cytokines on the expression of MHC antigens, complement receptors and other antigens on human blood monocytes and U937 cells: Role in cell differentiation, activation and phagocytosis. Immunology (1997) 90(2):286-293.
54. 3 works as anti-inflammatory. Diabetes Res Clin Pract (2007) 77(1):47-57.
55. Peterson CA, Heffernan ME: Serum tumor necrosis factor-α concentrations are negatively correlated with serum 25(OH)D concentrations in healthy women. J Inflamm (2008) 5:10.
56. Abraham J, Campbell CY, Cheema A, Gluckman TJ, Blumenthal RS, Danyi P: C-reactive protein in cardiovascular risk assessment: A review of the evidence. J Cardiometab Syndr (2007) 2(2):119-123.
57. Timms PM, Mannan N, Hitman GA, Noonan K, Mills PG, Syndercombe-Court D, Aganna E, Price CP, Boucher BJ: Circulating MMP9, vitamin D and variation in the TIMP-1 response with VDR genotype: Mechanisms for inflammatory damage in chronic disorders? QJM (2002) 95(12):787-796. (Pubitemid 36032948)
58. Van den Berghe G, Van Roosbroeck D, Vanhove P, Wouters PJ, De Pourcq L, Bouillon R: Bone turnover in prolonged critical illness: Effect of vitamin D. J Clin Endocrinol Metab (2003) 88(10):4623-4632. (Pubitemid 37357503)
59. Falk E: Pathogenesis of atherosclerosis. J Am Coll Cardiol (2006) 47(8):C7-C12.
60. Towler DA, Bidder M, Latifi T, Coleman T, Semenkovich CF: Diet-induced diabetes activates an osteogenic gene regulatory program in the aortas of low density lipoprotein receptor-deficient mice. J Biol Chem (1998) 273(46):30427-30434. (Pubitemid 28545516)
61. Mathew S, Lund RJ, Chaudhary LR, Geurs T, Hruska KA: Vitamin D receptor activators can protect against vascular calcification. J Am Soc Nephrol (2008) 19(8):1509-1519. • Presents data demonstrating that, in LDLR-/- mice with CKD, calcitriol or paricalcitol treatment at clinically relevant doses reduced neointimal vascular calcium content. However, when the concentration of paricalcitol was increased to a high level, further calcification was induced. It was suggested that VDR activators exerted a biphasic, dosage-dependent effect on the development of atherosclerotic plaques and calcification.
62. Taura S, Taura M, Kamio A, Kummerow FA: Vitamin D-induced coronary atherosclerosis in normolipemic swine: Comparison with human disease. Tohoku J Exp Med (1979) 129(1):9-16. (Pubitemid 10196771)
63. Kunitomo M, Kinoshita K, Bando Y: Experimental atherosclerosis in rats fed a vitamin D, cholesterol-rich diet. J Pharmacobiodyn (1981) 4(9):718-723. (Pubitemid 12234248)
64. Shimada T, Kakitani M, Yamazaki Y, Hasegawa H, Takeuchi Y, Fujita T, Fukumoto S, Tomizuka K, Yamashita T: Targeted ablation of FGF23 demonstrates an essential physiological role of FGF23 in phosphate and vitamin D metabolism. J Clin Invest (2004) 113(4):561-568. (Pubitemid 38542505)
65. Razzaque MS, Sitara D, Taguchi T, St-Arnaud R, Lanske B: Premature aging-like phenotype in fibroblast growth factor 23 null mice is a vitamin D-mediated process. FASEB J (2006) 20(6):720-722. (Pubitemid 46671193)
66. Ogren M, Bergqvist D, Wåhlander K, Eriksson H, Sternby NH: Trousseau's syndrome - What is the evidence? A population-based autopsy study. Thromb Haemost (2006) 95(3):541-545.
67. Büller HR, Agnelli G, Hull RD, Hyers TM, Prins MH, Raskob GE: Antithrombotic therapy for venous thromboembolic disease: The Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy. Chest (2004) 126(3 Suppl):401S-428S. (Pubitemid 39297960)
68. Franchini M, Montagnana M, Targher G, Manzato F, Lippi G: Pathogenesis, clinical and laboratory aspects of thrombosis in cancer. J Thromb Thrombolysis (2007) 24(1):29-38. • A review that discusses the relationship between increased clotting and malignancy, and the potential mechanisms responsible for the pathogenesis of thrombosis, as well as the laboratory, clinical and therapeutic features associated with cancer and thrombosis.
69. Lechner D, Weltermann A: Chemotherapy-induced thrombosis: A role for microparticles and tissue factor? Semin Thromb Hemost (2008) 34(2):199-203.
70. Worth LJ, Seymour JF, Slavin MA: Infective and thrombotic complications of central venous catheters in patients with hematological malignancy: Prospective evaluation of nontunneled devices. Support Care Cancer (2008) 17(7):811-818.
71. Gissel T, Rejnmark L, Mosekilde L, Vestergaard P: Intake of vitamin D and risk of breast cancer - A meta-analysis. J Steroid Biochem Mol Biol (2008) 111(3-5):195-199.
72. Pilz S, Dobnig H, Winklhofer-Roob B, Riedmüller G, Fischer JE, Seelhorst U, Wellnitz B, Boehm BO, März W: Low serum levels of 25-hydroxyvitamin D predict fatal cancer in patients referred to coronary angiography. Cancer Epidemiol Biomarkers Prev (2008) 17(5):1228-1233.
73. Fakih MG, Trump DL, Johnson CS, Tian L, Muindi J, Sunga AY: Chemotherapy is linked to severe vitamin D deficiency in patients with colorectal cancer. Int J Colorectal Dis (2009) 24(2):219-224.
74. Beer TM, Venner PM, Ryan CW, Petrylak DP, Chatta G, Dean Ruether J, Chi KN, Curd JG, DeLoughery TG: High dose calcitriol may reduce thrombosis in cancer patients. Br J Haematol (2006) 135(3):392-394. •• Presents data from a placebo-controlled, randomized clinical trial demonstrating that calcitriol significantly reduced the incidence of thrombotic events. (Pubitemid 44484849)
75. 3 were lower when compared with those obtained for white individuals, and thus the induction of cathelicidin mRNA expression was less efficient in this population.
76. Gombart AF, Bhan I, Borregaard N, Tamez H, Camargo CA Jr, Koeffler HP, Thadhani R: Low plasma level of cathelicidin antimicrobial peptide (hCAP18) predicts increased infectious disease mortality in patients undergoing hemodialysis. Clin Infect Dis (2009) 48(4):418-424.
77. Casserly LF, Dember LM: Thrombosis in end-stage renal disease. Semin Dial (2003) 16(3):245-256.
78. Zoccali C, Mallamaci F, Tripepi G: Inflammation and atherosclerosis in end-stage renal disease. Blood Purif (2003) 21(1):29-36. (Pubitemid 36173345)
79. Ebert R, Schutze N, Adamski J, Jakob F: Vitamin D signaling is modulated on multiple levels in health and disease. Mol Cell Endocrinol (2006) 248(1-2):149-159.
80. THE SALK INSTITUTE FOR BIOLOGICAL STUDIES/UNIVERSITY OF SYDNEY (Evans RM, Downes M, Liddle C): Use of vitamin D receptor agonists and precursors to treat fibrosis. WO-2009061961 (2009).
81. 3. WO-2005030222 (2005).
82. 3 compounds and methods of use thereof. WO-2006102647 (2006).
83. Tian J, Melnick JZ, Toner ES, Wu-Wong JR, Ostrow DH, Williams LA, Sun E, Kommala, DR: Use of vitamin Ds or vitamin D analogs to treat cardiovascular disease. US-20050209203 (2005).
84. Tian J, Melnick JZ, Toner ES, Wu-Wong JR, Ostrow DH, Williams LA, Sun E, Kommala DR: Use of vitamin D receptor activators or vitamin D analogs to treat cardiovascular disease. US-20060171983 (2006).
85. ABBOTT LABORATORIES (Von Geldern TW, Barkalow JH, Barnes DM, Haight AR, Hengeveld JE, Li X, McLaughlin MA, Noonan WT, Pei Z, Wu-Wong JR): Vitamin D receptor activators and methods of making. US-20090131379 (2009).
86. ABBOTT LABORATORIES (Von Geldern TW, Barkalow JH, Barnes DM, Haight AR, Hengeveld JE, Li X, McLaughlin MA, Noonan WT, Pei Z, Wu-Wong JR): New vitamin D receptor activators and methods of making. WO-2009067578 (2009).