Elsevier

Seminars in Nephrology

Volume 24, Issue 5, September 2004, Pages 456-459
Seminars in Nephrology

Vitamin D analogs: Actions and role in the treatment of secondary hyperparathyroidism

https://doi.org/10.1016/j.semnephrol.2004.06.013Get rights and content

Although calcitriol has been shown to have an important role in the pathogenesis of hyperparathyroidism, its use as a therapeutic agent often has been limited by calcemic and phosphatemic toxicity. Vitamin D analogs and the synthetic prohormones, with the potential to have lesser effects on calcium and phosphorus, have been introduced and shown to be effective therapeutic agents. Paricalcitol is used widely in the United States and may be associated with improved clinical outcomes. Further studies on the effects of these vitamin D sterols on the skeleton and further studies of potential differential effects on calcification processes will be forthcoming, and as the mechanisms of their lesser toxicity become understood, perhaps this will pave the way for a future generation of vitamin D analogs with even greater specificity for the suppression of hyperparathyroidism with lesser toxicity.

Section snippets

Paricalcitol

This vitamin D analog, also known as 19-nor-1,25-dihydroxyvitamin D2, was studied extensively and shown to be effective in suppressing PTH, with markedly lesser effects on increasing the levels of serum calcium or phosphorus.13 In experimental animals, paricalcitol effectively decreased the levels of PTH and was found to be 10 times less active than calcitriol in mobilizing calcium or phosphate from bone.14 Thus, this vitamin D analog could achieve a dissociation of the PTH suppressive effect

22-oxacalcitriol

22-oxacalcitriol is a vitamin D analog based on the vitamin D3 structure. The structural modification of insertion of an oxygen in the 22 position results in a decreased binding affinity of 22-oxacalcitriol for the vitamin D receptor, as well as for vitamin D–binding protein.22, 23, 24 The decreased binding to vitamin D–binding protein results in a very rapid clearance from the circulation. This phenomenon potentially may account for the apparent lesser toxicities of this vitamin D analog in

Falecalcitriol

Falecalcitriol is a vitamin D analog that has the substitution of hydrogen with fluorine at carbons 26 and 27. This modification results in prolonged biological activity owing to decreased metabolism of the vitamin D analog.30 In limited clinical studies, this analog also has been shown to effectively suppress hyperparathyroidism and is currently in clinical use.31

Vitamin D prohormones

The vitamin D prohormones, 1-α-hydroxyvitamin D3 (alfacalcidol) and 1-α-hydroxyvitamin D3 (doxercalciferol) are also in clinical use for the therapy of hyperparathyroidism. 1-α-hydroxyvitamin D2 has been in clinical use for a number of years and is used widely outside the United States.32, 33, 34, 35, 36 This vitamin D sterol becomes 25-hydroxylated in the liver after entry into the circulation and, therefore, becomes 1, 25-dihydroxyvitamin D3. This sterol has been shown to have similar

References (41)

  • M.C. Monier-Faugere et al.

    22-oxacalcitriol suppresses secondary hyperparathyroidism without inducing low bone turnover in dogs with renal failure

    Kidney Int

    (1999)
  • Y. Tsukamoto et al.

    Effect of 22-oxacalcitriol on bone histology of hemodialyzed patients with severe secondary hyperparathyroidism

    Am J Kidney Dis

    (2000)
  • T. Akiba et al.

    Controlled trial of falecalcitriol versus alfacalcidol in suppression of parathyroid hormone in hemodialysis patients with secondary hyperparathyroidism

    Am J Kidney Dis

    (1998)
  • G. Sjoden et al.

    Antirachitic activity of 1 alpha-hydroxyergocalciferol and 1 alpha-hydroxycholecalciferol in rats

    J Nutr

    (1984)
  • J.M. Frazao et al.

    Intermittent doxercalciferol (1alpha-hydroxyvitamin D(2)) therapy for secondary hyperparathyroidism

    Am J Kidney Dis

    (2000)
  • H.M. Maung et al.

    Efficacy and side effects of intermittent intravenous and oral doxercalciferol (1alpha-hydroxyvitamin D(2)) in dialysis patients with secondary hyperparathyroidismA sequential comparison

    Am J Kidney Dis

    (2001)
  • E.A. González et al.

    Renal osteodystrophypathogenesis and management

    Nephrol Dial Transplant

    (1995)
  • J. Silver et al.

    Regulation by vitamin D metabolites of parathyroid hormone gene transcription in vivo in the rat

    J Clin Invest

    (1986)
  • J. Russell et al.

    Suppression by 1,25(OH)2D3 of transcription of the pre-proparathyroid hormone gene

    Endocrinology

    (1986)
  • L.K. Cantley et al.

    1,25-dihydroxyvitamin D3 suppresses parathyroid hormone secretion from bovine parathyroid cells in tissue culture

    Endocrinology

    (1985)
  • Cited by (51)

    • Vitamin D receptor activation in a diabetic-like environment: Potential role in the activity of the endothelial pro-inflammatory and thioredoxin pathways

      2012, Journal of Steroid Biochemistry and Molecular Biology
      Citation Excerpt :

      The in vitro beneficial effects of these vitamin D analogs on the inflammatory process support the clinical findings reported in the literature [23,35,36]. Calcitriol suppresses PTH synthesis and secretion via VDR [22]. In addition, calcitriol was found to play an important role in renal, endothelial, and cardiovascular protection and to have antitumor activity [19,18].

    • Cardiorenal syndrome and vitamin D receptor activation in chronic kidney disease

      2012, Kidney Research and Clinical Practice
      Citation Excerpt :

      Some guidelines suggest correcting reduced 25-(OH)-D concentrations in CKD patients with an estimated GFR<60 mL/min/1.73 m2. Calcitriol and its analogs including vitamin D mimetics that activate VDR directly are commonly used to manage hyperparathyroidism secondary to CKD [94]. It has been shown that vitamin D3 supplementation reduces BP in patients with essential hypertension [95,96].

    View all citing articles on Scopus
    View full text