Comment on: Vitamin D analogs in denosumab-treated patients with kidney failure

Keywords::

• alfacalcidol
• calcitriol
• denosumab
• kidney failure

To the Editor

We read with interest the article “Calcitriol: a better option than vitamin D in denosumab-treated patients with kidney failure?” by Buonerba et al. [1]. Vitamin D3 and D2, produced by photosynthesis in the skin or ingested, are transported to the liver and metabolized to 25-hydroxyvitamin D, the major circulating form. Further hydroxylation occurs in the kidney to form the highly biologically active 1,25-dihydroxyvitamin D. As the authors note, 1-α-hydroxylation is progressively impaired in patients with a creatinine clearance < 70 ml/min. However, usually, there are no problems of availability of hepatic 25-hydroxylase and this activation is not impaired in liver disease except in very advanced stages of cirrhosis [2]. Alfacalcidol, 1-α-hydroxyvitamin D3, is another synthetic analog of vitamin D that is converted in the liver to the active metabolite 1,25-dihydroxyvitamin D. This analog has been useful in preventing bone mass loss in patients with advanced prostatic carcinoma after orchidectomy treated with complete androgenic blockade [3]. From a theoretical point of view, alfacalcidol could also be useful in denosumab-treated patients with kidney failure.

Declaration of interest

The authors have no competing interests to declare and have received no funding in preparation of the manuscript.

Bibliography

• Buonerba C, Caraglia M, Malgieri S, et al. Calcitriol: a better option than vitamin D in denosumab-treated patients with kidney failure? Expert Opin Biol Ther 2013;13(2):149-51
   PubMed Web of Science ®Google Scholar
• Ringe JD, Schacht E. Improving the outcome of established therapies for osteoporosis by adding the active D-hormone analog alfacalcidol. Rheumatol Int 2007;28(2):103-11
   Google Scholar
• Tałalaj M, Kapitan-Malinowska B, Debski K, et al. Administration of 1 alpha-OH vitamin D3 and calcium prevents bone mass loss in patients with advanced prostatic carcinoma after orchidectomy treated with complete androgenic blockade. Endokrynol Pol 2005;56(3):225-32
   Google Scholar

Author's response

Carlo Buonerba

University Federico II, Genitourinary Cancer Section, Medical oncology Division, Department of Endocrinology and oncology, Via Pansini, 5 80131 Naples, ltaly [email protected]

As the authors correctly state, alfacalcidol is likely to be equally effective with respect to calcitriol in reducing events of hypocalcemia in a selected population of patients receiving denosumab.

To my knowledge, hepatic hydroxylation is not regulated by serum calcium levels, so alfacalcidol should not provide any advantage over calcitriol in terms of hypercalcemia, as clinical evidence indicates [1]. An observational study with either of these agents is strongly warranted. I suggest that patients with kidney failure and severe hypocalcemia treated with denosumab and vitamin D should receive calcitriol in clinical practice.

Bibliography

• O'Donnell S, Moher D, Thomas K, et al. Systematic review of the benefits and harms of calcitriol and alfacalcidol for fractures and falls. J Bone Miner Metab 2008;26(6):531-42
   Google Scholar