Treatment of Hypovitaminosis D With Pharmacologic Doses of Cholecalciferol, Oral vs Intramuscular

An Open Labeled RCT

Mozhdeh Zabihiyeganeh; Adel Jahed; Marzieh Nojomi


Clin Endocrinol. 2013;78(2):210-216. 

In This Article

Abstract and Introduction


Objective Vitamin D deficiency is a worldwide health problem. Usual supplements are inadequate for prevention of hypovitaminosis D, and much higher doses are needed for its treatment. This study was designed to compare the efficacy and practicality of high-dose intramuscular and oral cholecalciferol in treatment of hypovitaminosis D and to evaluate durability of the effect of each remedy.

Design Ninety-two patients with hypovitaminosis D [serum 25(OH) D level < 75 nmol/l] were enrolled in a randomised clinical trial. Participants were randomly assigned to receive 300 000 IU cholecalciferol, either intramuscularly as a single injection or orally in six divided doses during 3 months period. Serum 25(OH) D level was measured at baseline and at 3 and 6 months.

Results Both treatment regimens significantly increased the serum 25(OH)D level. Delta change in serum 25(OH) D level from baseline (presented as mean ± SEM) at month 3 was significantly higher in oral than injection group (90 ± 11·2 and 58·8 ± 8·9 nmol/l, respectively, P = 0·03); but was similar at 6th month intervention (52·1 ± 7·6 and 62·2 ± 6·7 nmol/l, respectively, P = 0·32). There was a marginally significant trend in favour of oral group in the proportion of cases attained vitamin D adequacy at 6th month (P = 0·06); but still 15% of all patients remained at < 50 nmol/l.

Conclusion Both regimens were considerably effective, safe and practical in treating hypovitaminosis D. Although we revealed superiority of oral route, at least at early short time, the way of treatment may depend on the patient's choice, compliance and availability of various forms of the drug in any regions.


Vitamin D deficiency is now recognized as a pandemic.[1–8] It causes rickets in children and may precipitate or exacerbate musculoskeletal pain, fibromyalgia, osteopenia, osteoporosis and fractures in adults. Vitamin D deficiency has been associated with increased risk of common cancers, autoimmune diseases, hypertension, infectious diseases and even depression.[9–15] The major cause of vitamin D deficiency is inadequate exposure to sun light. Wearing sunscreen significantly reduces vitamin D synthesis in the skin. Very few foods naturally contain vitamin D and vitamin D-rich foods are often inadequate to satisfy vitamin D requirements. Using serum 25(OH)D level, measured by a reliable assay, is the standard test for vitamin D status. Although some controversies exist regarding the optimal level of serum 25(OH)D, based on its associations with PTH levels, and studies of calcium absorption and bone density, serum 25(OH)D may be classified as three different categories: deficiency, a 25(OH)D of < 50 nmol/l; insufficiency, a 25(OH)D of 50–74 nmol/l; and sufficiency, a 25(OH)D of 75–250 nmol/l.[16–22] Improving vitamin D status may have some positive effects on public health and may reduce health care costs for many chronic diseases.[23]

Despite its widespread deficiency and the increasing awareness of vitamin D importance in general health, there is little evidence available for its treatment. Cholecalciferol (D3) and ergocalciferol (D2) are equally effective in raising 25(OH)D level.[24] It has been shown the usual supplements are inadequate even for prevention; and much higher doses are needed for treatment. A physician may choose between high-dose oral or, if available, injectable forms of vitamin D; although the later form is unavailable in some developed countries. There are many unanswered clinical questions in using different pharmacoceutical forms of vitamin D, and because lack of comparing studies, it is even unclear whether to treat orally or by injection.

Considering all of these uncertainties, we conducted this head to head comparison study to evaluate oral and injectable routes in treatment of hypovitaminosis D. We aimed to assess the efficacy of each method, using the same dose of 300 000 IU D3, in achieving normal serum 25(OH)D level, the durability of the response, the practicality and the possible toxicity.