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Sent: Wednesday, August 19, 2009 9:51 PM

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Subject: Requested DocAlert: Vitamin D, at High Doses, Prevents Fractures Related to Osteoporosis

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Vitamin D, at High Doses, Prevents Fractures

Clinical question
Can vitamin D prevent important fractures related to osteoporosis?

Bottom line
Vitamin D at dosages greater than 400 IU per day is effective in decreasing nonvertebral fractures, including hip fractures. The effect is dose dependent; dosages less than 400 IU per day are ineffective. A practical way to implement this low-cost approach is to suggest nonprescription vitamin D supplements at dosages of 800 IU per day; that way, missed doses will still keep the average daily dose in the range of effectiveness. (LOE = 1a)

Reference
Bischoff-Ferrari HA, Willett WC, Wong JB, et al. Prevention of nonvertebral fractures with oral vitamin D dose dependency. A meta-analysis of randomized controlled trials. Arch Intern Med 2009;169(6):551-561. [PubMed Abstract]

Study design: Meta-analysis (randomized controlled trials)

Setting: Various (meta-analysis)

Synopsis
This meta-analysis, now the fourth on this topic in the past 5 years, went further than the other ones and looked at the relationship of dose and effectiveness of vitamin D in preventing nonvertebral fractures, especially hip fracture. To identify articles, the authors searched 3 databases, including the Cochrane Controlled Trials Register, and searched meeting abstracts and reference lists of identified articles, and contacted experts in the field. They identified 12 double-blind randomized controlled trials (enrolling a total of 42,279 patients with an average age of 78 years) that included data on how the fractures happened and data regarding adherence so they could calculate the received dosage of vitamin D. Data from the studies were independently abstracted by 3 researchers, then compared. Combining all trials, vitamin D supplementation produced a small decrease in nonvertebral fractures (relative risk = .86; 95% CI, .77 - .96). However, the results across studies were heterogeneous until they stratified study results by dosage. Dosages of 400 IU per day or less did not reduce nonvertebral fracture risk. Dosages of greater than 400 IU per day significantly reduced nonvertebral fractures, with 1 fracture prevented for every 93 patients treated with vitamin D instead of placebo for 12 months to 84 months (number needed to treat [NNT] = 93; 66-160). The effect was more pronounced with cholecalciferol (vitamin D3) than with erogocalciferol (vitamin D2) . Similarly, hip fractures were also prevented by higher dosages of vitamin D (NNT = 202; 114-823). The addition of calcium supplementation did not improve results.

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