The fields for clinical employment of vitamin D analogs are growing and under active evaluation in different medical specialties, ranging from dermatology to immunology and oncology. In this review we provide a brief description of the drugs that have been developed more specifically for the treatment of secondary hyperparathyroidism (SH) associated with uremia.
MorimotoS., KumaharaY.. A patient with psoriasis cured by 1-α-hydroxyvitamin D3.Med J Osaka Univ1985, 35: 51–4.
2.
ReichrathJ.. Vitamin D and the skin: an ancient friend, revisited.Exp Dermatol2007; 16: 618–25.
3.
HoughtonL.A., ViethR.. The case against ergocalciferol (vitamin D2) as a vitamin supplement.Am J Clin Nutr2006; 84: 694–7.
4.
SlatopolskyE., FinchJ., RitterC.. A new analog of calcitriol, 19-nor-1,25-(OH)2D2, suppresses parathyroid hormone secretion in uremic rats in the absence of hypercalcemia.Am J Kidney Dis1995; 26: 852–60.
5.
HollidayL.S., GluckS.L., SlatopolskyE., BrownA.J.. 1,25-Dihydroxy-19-nor-vitamin D(2), a vitamin D analog with reduced bone resorbing activity in vitro.J Am Soc Nephrol2000; 11: 1857–64.
6.
MartinK.J., GonzálezE.A., GellensM., HammL.L., AbboudH., LindbergJ.. 19-Nor-1-alpha-25-dihydroxyvitamin D2 (Paricalcitol) safely and effectively reduces the levels of intact parathyroid hormone in patients on hemodialysis.J Am Soc Nephrol1998; 9: 1427–32.
7.
LlachF., YuddM.. Paricalcitol in dialysis patients with calcitriol-resistant secondary hyperparathyroidism.Am J Kidney Dis2001; 38(Suppl 5): S45–50.
8.
SpragueS.M., LlachF., AmdahlM., TaccettaC., BatlleD.. Paricalcitol versus calcitriol in the treatment of secondary hyperparathyroidism.Kidney Int2003; 63: 1483–90.
9.
MartinK.J., GonzálezE., LindbergJ.S.. Paricalcitol dosing according to body weight or severity of hyperparathyroidism: a double-blind, multicenter, randomized study.Am J Kidney Dis2001; 38(Suppl 5): S57–63.
10.
MitsopoulosE., ZanosS., GinikopoulouE., KyriklidouP., MeimaridouD., SakellariouG.. Initial dosing of paricalcitol based on PTH levels in hemodialysis patients with secondary hyperparathyroidism.Am J Kidney Dis2006; 48: 114–21.
11.
DrüekeT.B., McCarronD.A.. Paricalcitol as compared with calcitriol in patients undergoing hemodialysis.N Engl J Med 2003; 31; 349: 496–9.
12.
TengM., WolfM., LowrieE., OfsthunN., LazarusJ.M., ThadhaniR.. Survival of patients undergoing hemodialysis with paricalcitol or calcitriol therapy.N Engl J Med2003; 349: 446–56.
13.
TengM., WolfM., OfsthunM.N.. Activated injectable vitamin D and hemodialysis survival: a historical cohort study.J Am Soc Nephrol2005; 16: 1115–25.
14.
Kalantar-ZadehK., KuwaeN., RegidorD.L.. Survival predictability of time-varying indicators of bone disease in maintenance hemodialysis patients.Kidney Int2006; 70: 771–80.
15.
TentoriF., HuntW.C., StidleyC.A.. Mortality risk among hemodialysis patients receiving different vitamin D analogs.Kidney Int2006; 70: 1858–65.
16.
ZhangZ., Sun SunL., WangY.. Renoprotective role of the vitamin D receptor on diabetic nephropathy.Kidney Int2008; 73: 163–71.
17.
MizobuchiM., MorrisseyJ., FinchJ.L.. Combination therapy with an angiotensin-converting enzyme inhibitor and a vitamin D analog suppresses the progression of renal insufficiency in uremic rats.J Am Soc Nephrol2007; 18: 1796–806.
18.
TanX., LiY., LiuY.. Paricalcitol attenuates renal interstitial fibrosis in obstructive nephropathy.J Am Soc Nephrol2006; 17: 3382–93.
CardúsA., PanizoS., ParisiE., FernandezE., ValdivielsoJ.M.. Differential effects of vitamin D analogs on vascular calcification.J Bone Miner Res2007; 22: 860–6.
21.
MizobuchiM., FinchJ.L., MartinD.R., SlatopolskyE.. Differential effects of vitamin D receptor activators on vascular calcification in uremic rats.Kidney Int2007; 72: 709–15.
22.
LopezI., MendozaF.J., Aguilera-TejeroE.. The effect of calcitriol, paricalcitol, and a calcimimetic on extraosseous calcifications in uremic rats.Kidney Int2008; 73: 300–7.
23.
BrownA.J., DussoA.S., SlatopolskyE.. Vitamin D analogues for secondary hyperparathyroidism.Nephrol Dial Transplant2002; 17(Suppl 10): S10–9.
24.
St-ArnaudR., ArabianA., YuV.W., AkhouayriO., KnutsonJ.C., StrugnellS.A.. 1alpha,24(S)(OH)2D2 normalizes bone morphology and serum parathyroid hormone without hypercalcemia in 25-hydroxyvitamin D-1-hydroxylase (CYP27B1)-deficient mice, an animal model of vitamin D deficiency with secondary hyperparathyroidism.J Endocrinol Invest2008; 31: 711–7.
25.
SjödenG., SmithC., LindgrenU., DeLucaH.F.. 1 alpha-Hydroxyvitamin D2 is less toxic than 1 alpha-hydroxyvitamin D3 in the rat.Proc Soc Exp Biol Med1985; 178: 432–6.
26.
BrownA.J., FinchJ.L., Lopez-HilkerS.. New active analogues of vitamin D with low calcemic activity.Kidney Int Suppl1990; 29: S22–7.
27.
TanA.U.Jr., LevineB.S., MazessR.B.. Effective suppression of parathyroid hormone by 1 alpha-hydroxy-vitamin D2 in hemodialysis patients with moderate to severe secondary hyperparathyroidism.Kidney Int1997; 51: 317–23.
28.
FrazaoJ.M., ChesneyR.W., CoburnJ.W.. Intermittent oral 1alpha-hydroxyvitamin D2 is effective and safe for the suppression of secondary hyperparathyroidism in haemodialysis patients. 1alphaD2 Study Group.Nephrol Dial Transplant1998; 13(Suppl 3): S68–72.
29.
MaungH.M., ElangovanL., FrazãoJ.M.. Efficacy and side effects of intermittent intravenous and oral doxercalciferol (1alpha-hydroxyvitamin D(2)) in dialysis patients with secondary hyperparathyroidism: a sequential comparison.Am J Kidney Dis2001; 37: 532–43.
30.
SlatopolskyE., CozzolinoM., FinchJ.L.. Differential effects of 19-nor-1,25-(OH)(2)D(2) and 1alpha-hydroxyvitamin D(2) on calcium and phosphorus in normal and uremic rats.Kidney Int2002; 62: 1277–84.
31.
ZismanA.L., GhantousW., SchinleberP., RobertsL., SpragueS.M.. Inhibition of parathyroid hormone: a dose equivalency study of paricalcitol and doxercalciferol.Am J Nephrol2005; 25: 591–5.
32.
van GinkelP.R., YangW., MarcetM.M.. 1 alpha-Hydroxyvitamin D2 inhibits growth of human neuroblastoma.J Neurooncol2007; 85: 255–62.
33.
GrosternR.J., BryarP.J., ZimbricM.L.. Toxicity and dose-response studies of 1alpha-hydroxyvitamin D2 in a retino-blastoma xenograft model.Arch Ophthalmol2002; 120: 607–12.
34.
AttiaS., EickhoffJ., WildingG.. Randomized, double-blinded phase II evaluation of docetaxel with or without doxercalciferol in patients with metastatic, androgen-independent prostate cancer.Clin Cancer Res2008; 14: 2437–43.
35.
PetrichA., KahlB., BaileyH., KimK., TurmanN., JuckettM.. Phase II study of doxercalciferol for the treatment of myelodysplastic syndrome.Leuk Lymphoma2008; 49: 57–61.
36.
BrownA.J., FinchJ., GrieffM.. The Mechanism for the Disparate Actions of calcitriol and 22-Oxacalcitriol in the Intestine.Endocrinology1993; 133: 1158–64.
37.
KobayashiT., TsugawaN., OkanoT.. The Binding Properties, with Blood Proteins, and Tissue Distribution of 22-Oxa-1alfa,25-Dihydroxyvitamin D3, a Noncalcemic Analogue of 1alfa- Dihydroxyvitamin D3, in Rats.J Biochem1994; 115: 373–80.
38.
TakeyamaK., MasuhiroY., FuseH.. Selective Interaction of Vitamin D Receptor with Transcriptional Coactivators by a Vitamin Analog.Mol Cell Biol1999; 19: 1049–55.
39.
Monier-FaugereM.C., GengZ., FriedlerR.M.. 22-Oxacalcitriol suppresses secondary hyperparathyroidism without inducing low bone turnover in dogs with renal failure.Kidney Int1999; 55: 821–32.
40.
ShiizakiK., NegiS., HatamuraI.. Biochemical and Cellular Effects of Direct Maxacalcitol Injection into Parathyroid Gland in Uremic Rats.J Am Soc Nephrol2005; 16: 97–108.
41.
OkunoS., IshimuraE., KitataniK.. Relationship between parathyroid gland size and responsiveness to maxacalcitol therapy in patients with secondary hyperparathyroidism.Nephrol Dial Transplant2003; 18: 2613–21.
42.
TominagaY., MatsuokaS., SatoT.. Clinical Features and Hyperplastic Patterns of Parathyroid Glands in Hemodialysis Patients With Advanced Secondary Hyperparathyroidism Refractory to Maxacalcitol Treatment and Required Parathyroidectomy.Ther Apher Dial2007; 11: 266–73.
43.
BarkerJ.N., AshtonR.E., MarksR.. Topical Maxacalcitol for the treatment of psoriasis vulgaris: a placebo-controlled, double-blind, dose-finding study with active comparator.Br J Dermatol1999; 141: 274–8.
44.
KomineM., WatabeY., ShimaokaS.. The action of a novel vitamin D3 analogue, OCT, on immunomodulatory function of keratinocytes and lymphocytes.Arch Dermatol Res1999; 291: 500–6.
45.
NakagawaK., SasakiY., KatoS., KuboderaN., OkanoT.. 22-Oxa,1alfa,25-Dihydroxyvitamin D3 inhibits metastasis and angiogenesis in lung cancer.Carcinogenesis2005; 26: 1044–54.
46.
NakatsukaK., ImanishiY., MorishimaY.. Biological potency of a fluorinated vitamin D analogue in yperparathyroidism.Bone Miner1992; 16: 73–81.
47.
KomuroS., SatoM., KanamaruH.. Disposition and metabolism of F6–1alpha,25(OH)2vitaminaD3 and 1alpha,25(OH)2vitaminD3 in the parathyroid glands of rats dosed with tritiumlabeled compounds.Drug Metab Dispos2003; 31: 973–8.
48.
HondaA., NakashimaN., ShidaY., MoriY., NagataA., IshizukaS.. Modification of 1alpha,25(OH)2vitaminD3 metabolism by introduction of26,26,26,27,27,27-hexafluoro atoms in human promyelocytic leukaemia (HL-60) cells: isolation and identification of a novel bioactive metabolite, 26, 26, 26, 27, 27, 27-hexafluoro-1,23(S), 25triihydroxyvitaminD3.Biochem J1993; 295(Pt 2): 509–16.
49.
TanakaY., DeLucaH.F., KobayashiY., IkekawaN.. 26,26,26,27,27,27-hexafluoro-1,25-dihydroxyvitaminD3: a highly potent, long-lasting analogue of 1alpha,25(OH)2vitaminD3.Arch Biochem Biophys1984; 229: 348–54.
50.
AkibaT., MarumoF., OwadaA.. Controlled trial of falecalcitriol versus alfacalcidol in suppression of parathyroid hormone in hemodialysis patients with secondary hyperparathyroidism.Am J Kidney Dis1998; 32: 238–46.
51.
NishizawaY., MoriiH., OguraY., De LucaH.F.. Clinical trail fo 26,26,26,27,27,27-hexafluoro-1,25-dihydroxyvitaminD3 in uremic patients on hemodialysis: preliminary report.Contrib Nephrol1991; 90: 196–203.
52.
SlatopolskyE., FinchJ.L., BrownA.J.. Effect of 2-Methylene-19-nor-20(S)-1α-Hydroxy-Bis-homo-pregnacalciferol (2MbisP), an Analog of Vitamin D, on Secondary Hyperparathyroidism.J Bone Miner Res2007; 22: 686–94.
53.
BrownA.J., SlatopolskyE.. Vitamin D analogs: Therapeutic applications and mechanisms for selectivity.Mol Aspects Med2008; 29: 433–52.
54.
WilliamsK.B., DeLucaH.F.. 2-Methylene-19-nor-20(S)-1α-Hydroxy-Bis-homo-pregnacalciferol(2MbisP), does not stimulate intestinal phosphate absorption at levels previously shown to suppress parathyroid hormone.Steroids2008; 73: 1277–84.
