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Vitamin D2 Treatment for Vitamin D Deficiency and Insufficiency for Up to 6 Years FREE

Sara M. Pietras, MD; Busayo K. Obayan, BA; Mona H. Cai, BS, MPH; Michael F. Holick, PhD, MD
Arch Intern Med. 2009;169(19):1806-1818. doi:10.1001/archinternmed.2009.361.
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The worldwide prevalence of vitamin D deficiency is striking, and more than 40% of the population may be vitamin D deficient.1 Despite this, to our knowledge there are no long-term studies of the safety and efficacy of giving pharmacologic doses of vitamin D (50 000 IU of ergocalciferol [vitamin D2]) to treat and prevent vitamin D deficiency. Furthermore, there is a concern that ergocalciferol, the only pharmaceutical vitamin D available in the United States, may be less effective than cholecalciferol (vitamin D3).2 In our clinic, which specializes in metabolic bone disease, we routinely treat vitamin D deficiency (serum 25-hydroxyvitamin D [25(OH)D] levels <20 ng/mL [to convert to nanomoles per liter, multiply by 2.496]) with 50 000 IU of ergocalciferol once a week for 8 weeks.1,3 The efficacy of this regimen has been previously described.1 To prevent recurrent vitamin D deficiency and also to maintain adequate levels in patients who are vitamin D sufficient, we treat with 50 000 IU of ergocalciferol every other week indefinitely, a regimen that, to our knowledge, has not been published to date.

We conducted a retrospective medical record review of visits from January 1, 2001, to May 1, 2007. Approximately 200 medical records were reviewed. We included patients 18 years or older with 2 or more measurements of 25(OH)D level, who received maintenance therapy with 50 000 IU of ergocalciferol every other week. All 25(OH)D samples were analyzed at Quest Diagnostics, Madison, New Jersey. Eighty-six patients (mean [range] age, 61 [18-91] years; 79% female) had a mean (range) treatment duration of 26 (5-72) months.

Prior to treatment, 79 patients (92%) had 25(OH)D levels lower than 30 ng/mL. The mean (SD) 25(OH)D level prior to treatment was 23.4 (9.5) ng/mL, while the mean (SD) level at the end of the review was 47.0 (18.2) ng/mL (P < .001) (Figure, A). At the last review, 14 patients (16%) had 25(OH)D levels lower than 30 ng/mL.

Place holder to copy figure label and caption
Figure.

Mean serum 25-hydroxyvitamin D (25[OH]D) and calcium levels. Results are given as mean (SEM) values averaged over 6-month intervals. Time 0 is initiation of treatment. A, Mean 25 (OH) D levels in all patients treated with 50 000 IU of ergocalciferol (vitamin D2) every 2 weeks (maintenance therapy, n = 86). Forty-one of the patients were vitamin D insufficient or deficient and first received 50 000-IU ergocalciferol weekly for 8 weeks before being placed on maintenance therapy of 50 000 IU of ergocalciferol every 2 weeks. The mean 25(OH)D level of each 6-month interval was compared with initial mean 25(OH)D level and showed a significant difference of P < .001 for all time points. To convert 25(OH)D to nanomoles per liter, multiply by 2.496. B, Mean serum 25(OH)D levels in patients receiving maintenance therapy only. There were 38 patients who were vitamin D insufficient (25[OH]D levels <21-29 ng/mL and 7 patients who were vitamin D sufficient (25[OH]D levels ≥30 ng/mL) who were treated only with maintenance therapy of 50 000 IU of ergocalciferol (vitamin D2) every 2 weeks. The mean 25(OH)D levels in each 6-month interval were compared with mean initial 25(OH)D levels and showed a significant difference of P < .001 for all time points up to 48 months. The data for interval months 60 and 72 were pooled, and there was a significant difference of P < .01 compared with the baseline value. C, Serum calcium levels. Results for all 86 patients who were treated with 50 000 IU of ergocalciferol (vitamin D2). The reference range for serum calcium level is 8.5 to 10.2 mg/dL (to convert to millimoles per liter, multiply by 0.25).

Graphic Jump Location

We treated some patients with vitamin D deficiency or insufficiency (levels <30 ng/mL) first with 50 000 IU of ergocalciferol weekly prior to maintenance therapy. Of the 86 patients studied, 41 who were vitamin D deficient or insufficient received 8 weeks of 50 000 IU of ergocalciferol weekly prior to starting maintenance therapy. For those patients, the mean (SD) pretreatment 25(OH)D level was 19.3 (6.2) ng/mL, which increased to 37.2 (13.0) ng/mL after 8 weeks of weekly therapy (P < .001). These patients were then treated with 50 000 IU of ergocalciferol every other week and had a mean (SD) final 25(OH)D level of 46.9 (18.6) ng/mL (P < .001).

For the 45 patients who received only maintenance therapy of 50 000 IU of ergocalciferol every 2 weeks, the mean (SD) pretreatment 25(OH)D level was 26.9 (10.6) ng/mL, and the mean (SD) final level was 47.1 (18.0) ng/mL (P < .001) (Figure, B). Mean (SD) serum calcium levels did not change (pretreatment, 9.5 [0.7] mg/dL; final, 9.6 [0.6] mg/dL [to convert to millimoles per liter, multiply by 0.25]; P = .20 [Figure, C]). There were no incidents of kidney stones or evidence of vitamin D intoxication.1

There have been several strategies to treat vitamin D deficiency, including 600 IU of cholecalciferol daily, 4200 IU weekly, and 18 000 IU monthly.4 These studies have shown only partial efficacy and have been short in duration. No studies have been longer than 1 year. Little is known as to whether pharmacologic doses of ergocalciferol either become ineffective over time or accumulate in body fat stores, producing vitamin D intoxication.

Our experience shows that 50 000 IU of ergocalciferol weekly for 8 weeks effectively treats vitamin D deficiency, and continued treatment with 50 000 IU of ergocalciferol every other week for up to 6 years prevents recurrent vitamin D deficiency in most patients. However, 16% of our patients remained vitamin D deficient or insufficient. Results from further investigation showed that 6 of those patients either were not taking their medication or were taking corticosteroids or antiseizure medications, which can affect vitamin D metabolism. We did not find a reason for persistent vitamin D deficiency in the remaining 8 patients, although we suspect it may be due to medication nonadherence.

It bears mention that the cost of this therapy is low; pills can be purchased without insurance for as little as $66 per year for maintenance therapy. The cost of testing is $40 by Medicare payment schedules, though some commercial laboratories charge as much as $200 per test. Insurance companies generally consider ergocalciferol a tier 1 medication. Ergocalciferol is therefore effective in raising serum 25(OH)D level when given in physiologic5 and pharmacologic doses and is a simple method to treat and prevent vitamin D deficiency.

Correspondence: Dr Holick, Division of Endocrinology, Diabetes & Nutrition, Boston Medical Center, 85 E Newton St, Room 1013, Boston, MA 02118 (mfholick@bu.edu).

Author Contributions:Study concept and design: Holick. Acquisition of data: Pietras, Obayan, and Holick. Analysis and interpretation of data: Pietras, Obayan, Cai, and Holick. Drafting of the manuscript: Pietras, Obayan, Cai, and Holick. Critical revision of the manuscript for important intellectual content: Pietras and Holick. Statistical analysis: Obayan and Cai. Obtained funding: Obayan and Holick. Administrative, technical, and material support: Holick. Study supervision: Pietras and Holick.

Financial Disclosure: None reported.

Holick  MF Vitamin D deficiency. N Engl J Med 2007;357 (3) 266- 281
PubMed
Armas  LAHollis  BWHeaney  RP  Vitamin D2 is much less effective than vitamin D3 in humans.  J Clin Endocrinol Metab 2004;89 (11) 5387- 5391
PubMed
Malabanan  AVeronikis  IEHolick  MF Redefining vitamin D insufficiency. Lancet 1998;351 (9105) 805- 806
PubMed
Chel  VWijnhoven  HASmit  JHOoms  MLips  P Efficacy of different doses and time intervals of oral vitamin D supplementation with or without calcium in elderly nursing home residents. Osteoporos Int 2008;19 (5) 663- 671
PubMed
Holick  MFBiancuzzo  RMChen  TC  et al.   Vitamin D2 is as effective as vitamin D3 in maintaining circulating concentrations of 25-hydroxyvitamin D.  J Clin Endocrinol Metab 2008;93 (3) 677- 681
PubMed

Figures

Place holder to copy figure label and caption
Figure.

Mean serum 25-hydroxyvitamin D (25[OH]D) and calcium levels. Results are given as mean (SEM) values averaged over 6-month intervals. Time 0 is initiation of treatment. A, Mean 25 (OH) D levels in all patients treated with 50 000 IU of ergocalciferol (vitamin D2) every 2 weeks (maintenance therapy, n = 86). Forty-one of the patients were vitamin D insufficient or deficient and first received 50 000-IU ergocalciferol weekly for 8 weeks before being placed on maintenance therapy of 50 000 IU of ergocalciferol every 2 weeks. The mean 25(OH)D level of each 6-month interval was compared with initial mean 25(OH)D level and showed a significant difference of P < .001 for all time points. To convert 25(OH)D to nanomoles per liter, multiply by 2.496. B, Mean serum 25(OH)D levels in patients receiving maintenance therapy only. There were 38 patients who were vitamin D insufficient (25[OH]D levels <21-29 ng/mL and 7 patients who were vitamin D sufficient (25[OH]D levels ≥30 ng/mL) who were treated only with maintenance therapy of 50 000 IU of ergocalciferol (vitamin D2) every 2 weeks. The mean 25(OH)D levels in each 6-month interval were compared with mean initial 25(OH)D levels and showed a significant difference of P < .001 for all time points up to 48 months. The data for interval months 60 and 72 were pooled, and there was a significant difference of P < .01 compared with the baseline value. C, Serum calcium levels. Results for all 86 patients who were treated with 50 000 IU of ergocalciferol (vitamin D2). The reference range for serum calcium level is 8.5 to 10.2 mg/dL (to convert to millimoles per liter, multiply by 0.25).

Graphic Jump Location

Tables

References

Holick  MF Vitamin D deficiency. N Engl J Med 2007;357 (3) 266- 281
PubMed
Armas  LAHollis  BWHeaney  RP  Vitamin D2 is much less effective than vitamin D3 in humans.  J Clin Endocrinol Metab 2004;89 (11) 5387- 5391
PubMed
Malabanan  AVeronikis  IEHolick  MF Redefining vitamin D insufficiency. Lancet 1998;351 (9105) 805- 806
PubMed
Chel  VWijnhoven  HASmit  JHOoms  MLips  P Efficacy of different doses and time intervals of oral vitamin D supplementation with or without calcium in elderly nursing home residents. Osteoporos Int 2008;19 (5) 663- 671
PubMed
Holick  MFBiancuzzo  RMChen  TC  et al.   Vitamin D2 is as effective as vitamin D3 in maintaining circulating concentrations of 25-hydroxyvitamin D.  J Clin Endocrinol Metab 2008;93 (3) 677- 681
PubMed

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