Annual intramuscular injection of a megadose of cholecalciferol for treatment of vitamin D deficiency: efficacy and safety data

Aim: To evaluate the efficacy and safety of an annual intramuscular injection of cholecalciferol for vitamin D deficiency. Design: Prospective open-label study. Participants: Five men and 45 women (mean age 66.3 years) with vitamin D deficiency who were given a single therapeutic intramuscular injection of 600 000 IU (15 mg) cholecalciferol (vitamin D₃). Outcome measures: Serum levels of calcium, creatinine, 25-hydroxyvitamin D₃ (25OHD₃) and parathyroid hormone, as well as early morning 2-hour urine calcium/creatinine excretion index. Specimens were collected at baseline and after 4 and 12 months of therapy. Data are reported as mean±1 SD. Results: Vitamin D deficiency was severe (< 12.5 nmol/L) in one participant, moderate (12.5-24 nmol/L) in 14, and mild (25-49 nmol/L) in 35. Twenty-four participants (48%) had secondary hyperparathyroidism. Following intramuscular cholecalciferol injection, serum 25OHD₃ levels normalised in all participants and remained above 50 nmol/L throughout the study. Serum 25OHD₃ levels were significantly higher at 4 months (114±35 nmol/L), and 12 months (73±13 nmol/L) compared with baseline (32±8 nmol/L) (P<0.001), increasing by an average of 128% over the 12 months. There was a corresponding decrease in serum parathyroid hormone levels at 4 months (6±3 pmol/L) and at 12 months (5.2±3 pmol/L), with a 30% decrease at 12 months from baseline (7.4±4 pmol/L) (P<0.01). Primary hyperparathyroidism was unmasked in one participant at 4 months and mild hypercalcaemia (serum calcium, < 2.70 mmol/L) was noted in two participants (4%) at 12 months. Serum creatinine levels remained normal in all participants throughout the study, while increases in 2-hour urine calcium/creatinine excretion index were seen in 10 participants (20%) at 12 months, three of whom had elevated values at baseline. Conclusions: Once-yearly intramuscular cholecalciferol injection (600 000 IU) is effective therapy for vitamin D deficiency. While this therapy appears to be safe, the potential for developing hypercalciuria needs to be examined in a large randomised controlled trial.