Volume 176 - Issue 5
Vitamin D deficiency and multicultural Australia
Authors: Paul Glendenning, Rebecca S Mason and Terrence H Diamond
Med J Aust 2002; 176 (5): 242-243. || doi: 10.5694/j.1326-5377.2002.tb04389.x
Published online: 4 March 2002
Published online: 4 March 2002
To the Editor: In a recent editorial, Mason and Diamond state that ergocalciferol (vitamin D2) is bioequivalent to cholecalciferol (vitamin D3) and that 1000 IU/day of ergocalciferol is sufficient for the treatment of vitamin D deficiency.1 Both statements are contentious. Although ergocalciferol (vitamin D2) is the only single prohormonal form of vitamin D available on prescription in Australia, there are three reasons to be cautious about the use and dose equivalence of ergocalciferol (vitamin D2) compared with cholecalciferol (vitamin D3).
Cholecalciferol (and not ergocalciferol) has been shown in two randomised trials to reduce fracture rates when administered concomitantly with calcium to elderly patients.2,3 Furthermore, all recently studied agents for treating postmenopausal osteoporosis (alendronate, risedronate, raloxifene and parathyroid hormone 1-34 [the first 34 amino acids of the hormone]) were shown to lower fracture rates, but study participants were routinely given supplementary calcium and vitamin D when deficiency was established. At least two studies specified the use of cholecalciferol.
Vitamin D2 (ergocalciferol) and vitamin D3 (cholecalciferol) are probably not bioequivalent.4,5 Ergocalciferol administration to vitamin-D-replete premenopausal women reduced the amount of circulating 25-hydroxyvitamin D3 (25OHD3) while only modestly increasing 25OHD2 levels, with a resultant marginal effect on the total 25OHD level.4 In contrast, the equivalent dose of cholecalciferol increased the circulating level of 25OHD3 significantly.4
Lastly, while radioimmunoassays (RIAs), such as the INCSTAR/DioSorin assay (Stillwater, Minnesota, USA), used in both studies of vitamin D levels published recently in the MJA6,7 are able to measure 25OHD levels, they are incapable of differentiating between 25OHD2 and 25OHD3. Furthermore, neither of the commercially available RIAs (the other one is made by IDS Ltd, Tyne and Wear, UK) is able to measure both vitamin D metabolites with equivalent accuracy. In a study comparing RIAs for the measurement of 25OHD against high performance liquid chromatography (the gold standard method) both assays did not recognise 25OHD2 as well as 25OHD3, with r2 of 0.74 and 0.58, respectively, for 25OHD2.8 Until further research is available, using more patients and a greater number with vitamin D deficiency, caution must be exercised in the interpretation of 25OHD levels measured with RIAs. This applies especially to individuals taking ergocalciferol (vitamin D2) for the treatment of vitamin D deficiency.
Thus, it would appear that cholecalciferol (vitamin D3 ) has a role to play in the reduction of osteoporotic fractures, but only when administered with calcium. If administering ergocalciferol (vitamin D2), a far greater dose than 1000 IU/day may be needed, and the use of commercial RIAs to determine the therapeutic response may be misleading.
Competing interests
None declared.
References
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- Chapuy MC, Arlot ME, Duboeuf F, et al. Vitamin D3 and calcium to prevent hip fractures in elderly women. N Engl J Med 1992; 327: 1637-1642. i1146953
- Dawson-Hughes B, Harris SS, Krall EA, Dallal GE. Effect of calcium and vitamin D supplementation on bone density in men and women 65 years of age or older. N Engl J Med 1997; 337: 670-676. i1146955
- Tjellesen L, Hummer L, Christiansen C, Rodbro P. Serum concentration of vitamin D metabolites during treatment with vitamin D2 and D3 in normal premenopausal women. Bone Miner 1986; 1: 407-413. i1146957
- Trang HM, Cole DE, Rubin LA, et al. Evidence that vitamin D3 increases serum 25-hydroxyvitamin D more efficiently than does vitamin D2. Am J Clin Nutr 1998; 68: 854-858. i1146959
- Grover SR, Morley R. Vitamin D deficiency in veiled or dark-skinned pregnant women. Med J Aust 2001; 175: 251-252. i1146961
- Nozza JM, Rodda CP. Vitamin D deficiency in mothers of infants with rickets. Med J Aust 2001; 175: 253-255. i1146963
- Hollis BW. Comparison of commercially available (125)I-based RIA methods for the determination of circulating 25-hydroxyvitamin D. Clin Chem 2000; 46: 1657-1661. i1146965
- Holick MF. Vitamin D: Photobiology, metabolism, mechanism of action, and clinical applications. In: Favus M, editor. Primer on the metabolic bone diseases and disorders of mineral metabolism. Philadelphia: Lippincott Williams & Wilkins, 1999: 92-98. BGJBIBDA
- Trang HM, Cole DEC, Rubin LA, et al. Evidence that vitamin D3 increases serum 25-hydroxyvitamin D more efficiently than does vitamin D2. Am J Clin Nutr 1998; 68: 854-858. BGJEEBCE
- Gertner JM, Domenech M. 25-Hydroxyvitamin D levels in patients treated with high-dosage ergo- and cholecalciferol. Clin Path 1977; 30: 144-150. i1146925
- Tjellesen L, Gotfredsen A, Christiansen C. Different actions of vitamin D2 and D3 on bone metabolism in patients treated with phenobarbitone/phenytoin. Calcif Tissue Int 1985; 37: 218-222.
- Chapuy MC, Chapuy P, Meunier PJ. Calcium and vitamin D supplements: effects on calcium metabolism in elderly people. Am J Clin Nutr 1987; 46: 324-328.