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

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.

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.