高容量経口ビタミンDで転倒と骨折が増加

高容量経口ビタミンDで転倒と骨折が増加したという論文を紹介します。この論文の存在は、名郷直樹先生に教えていただきました。どうもありがとうございます。

Sanders KM, Stuart AL, Williamson EJ, Simpson JA, Kotowicz MA, Young D, Nicholson GC: Annual high-dose oral vitamin D and falls and fractures in older women: a randomized controlled trial. JAMA. 2010 May 12;303(18):1815-22.

この論文は全文見ることができるようです。

1年に1回秋から冬に50万IUのビタミンDもしくはプラセボを地域在住の高齢女性に投与して、転倒と骨折を評価した大規模なランダム化比較試験です。

結果としてビタミンD投与群では転倒のリスク（1.15; 95%CI, 1.02-1.30）と骨折のリスク（1.26; 95% CI, 1.00-1.59）が有意に増加しました。特に投与後最初の3ヶ月間で、その後の9ヶ月間より転倒が多いという結果でした。

ビタミンDは転倒予防に有効というメタ分析があるのに（有効でないというメタ分析もありますが）、1年に1回の経口投与ではむしろ転倒が増えるという逆の結果です。少なくとも高容量ビタミンDの単回経口投与は行うべきではないといえます。ビタミンDの研究論文は少なからずありますが、結果が一定しないのが本当に困ります。これが現実かもしれませんが。

Abstract
CONTEXT: Improving vitamin D status may be an important modifiable risk factor to reduce falls and fractures; however, adherence to daily supplementation is typically poor.

OBJECTIVE: To determine whether a single annual dose of 500,000 IU of cholecalciferol administered orally to older women in autumn or winter would improve adherence and reduce the risk of falls and fracture.

DESIGN, SETTING, AND PARTICIPANTS: A double-blind, placebo-controlled trial of 2256 community-dwelling women, aged 70 years or older, considered to be at high risk of fracture were recruited from June 2003 to June 2005 and were randomly assigned to receive cholecalciferol or placebo each autumn to winter for 3 to 5 years. The study concluded in 2008.

INTERVENTION: 500,000 IU of cholecalciferol or placebo.

MAIN OUTCOME MEASURES: Falls and fractures were ascertained using monthly calendars; details were confirmed by telephone interview. Fractures were radiologically confirmed. In a substudy, 137 randomly selected participants underwent serial blood sampling for 25-hydroxycholecalciferol and parathyroid hormone levels.

RESULTS: Women in the cholecalciferol (vitamin D) group had 171 fractures vs 135 in the placebo group; 837 women in the vitamin D group fell 2892 times (rate, 83.4 per 100 person-years) while 769 women in the placebo group fell 2512 times (rate, 72.7 per 100 person-years; incidence rate ratio [RR], 1.15; 95% confidence interval [CI], 1.02-1.30; P = .03). The incidence RR for fracture in the vitamin D group was 1.26 (95% CI, 1.00-1.59; P = .047) vs the placebo group (rates per 100 person-years, 4.9 vitamin D vs 3.9 placebo). A temporal pattern was observed in a post hoc analysis of falls. The incidence RR of falling in the vitamin D group vs the placebo group was 1.31 in the first 3 months after dosing and 1.13 during the following 9 months (test for homogeneity; P = .02). In the substudy, the median baseline serum 25-hydroxycholecalciferol was 49 nmol/L. Less than 3% of the substudy participants had 25-hydroxycholecalciferol levels lower than 25 nmol/L. In the vitamin D group, 25-hydroxycholecalciferol levels increased at 1 month after dosing to approximately 120 nmol/L, were approximately 90 nmol/L at 3 months, and remained higher than the placebo group 12 months after dosing.

CONCLUSION: Among older community-dwelling women, annual oral administration of high-dose cholecalciferol resulted in an increased risk of falls and fractures.