Appel Lawrence J, Michos Erin D, Mitchell Christine M, Blackford Amanda L, Sternberg Alice L, Miller Edgar R, Juraschek Stephen P, Schrack Jennifer A, Szanton Sarah L, Charleston Jeanne, Minotti Melissa, Baksh Sheriza N, Christenson Robert H, Coresh Josef, Drye Lea T, Guralnik Jack M, Kalyani Rita R, Plante Timothy B, Shade David M, Roth David L, Tonascia James
Johns Hopkins University, Baltimore, Maryland (L.J.A., E.R.M., D.L.R.).
Johns Hopkins University School of Medicine, Baltimore, Maryland (E.D.M., A.L.B., R.R.K.).
Ann Intern Med. 2021 Feb;174(2):145-156. doi: 10.7326/M20-3812. Epub 2020 Dec 8.
Vitamin D supplementation may prevent falls in older persons, but evidence is inconsistent, possibly because of dosage differences.
To compare the effects of 4 doses of vitamin D supplements on falls.
2-stage Bayesian, response-adaptive, randomized trial. (ClinicalTrials.gov: NCT02166333).
2 community-based research units.
688 participants, aged 70 years and older, with elevated fall risk and a serum 25-hydroxyvitamin D [25-(OH)D] level of 25 to 72.5 nmol/L.
200 (control), 1000, 2000, or 4000 IU of vitamin D per day. During the dose-finding stage, participants were randomly assigned to 1 of the 4 vitamin D doses, and the best noncontrol dose for preventing falls was determined. After dose finding, participants previously assigned to receive noncontrol doses received the best dose, and new enrollees were randomly assigned to receive 200 IU/d or the best dose.
Time to first fall or death over 2 years (primary outcome).
During the dose-finding stage, the primary outcome rates were higher for the 2000- and 4000-IU/d doses than for the 1000-IU/d dose, which was selected as the best dose (posterior probability of being best, 0.90). In the confirmatory stage, event rates were not significantly different between participants with experience receiving the best dose (events and observation time limited to the period they were receiving 1000 IU/d; = 308) and those randomly assigned to receive 200 IU/d ( = 339) (hazard ratio [HR], 0.94 [95% CI, 0.76 to 1.15]; = 0.54). Analysis of falls with adverse outcomes suggested greater risk in the experience-with-best-dose group versus the 200-IU/d group (serious fall: HR, 1.87 [CI, 1.03 to 3.41]; fall with hospitalization: HR, 2.48 [CI, 1.13 to 5.46]).
The control group received 200 IU of vitamin D per day, not a placebo. Dose finding ended before the prespecified thresholds for dose suspension and dose selection were reached.
In older persons with elevated fall risk and low serum 25-(OH)D levels, vitamin D supplementation at doses of 1000 IU/d or higher did not prevent falls compared with 200 IU/d. Several analyses raised safety concerns about vitamin D doses of 1000 IU/d or higher.
National Institute on Aging.
补充维生素D可能预防老年人跌倒，但证据并不一致，这可能是由于剂量差异所致。
比较4种剂量的维生素D补充剂对跌倒的影响。
两阶段贝叶斯响应自适应随机试验。（ClinicalTrials.gov注册号：NCT02166333）。
2个社区研究单位。
688名年龄在70岁及以上、跌倒风险增加且血清25-羟维生素D[25-(OH)D]水平为25至72.5 nmol/L的参与者。
每天补充200（对照）、1000、2000或4000国际单位的维生素D。在剂量探索阶段，参与者被随机分配到4种维生素D剂量中的一种，并确定预防跌倒的最佳非对照剂量。剂量探索结束后，之前被分配接受非对照剂量的参与者接受最佳剂量，新入组者被随机分配接受200国际单位/天或最佳剂量。
2年内首次跌倒或死亡的时间（主要结局）。
在剂量探索阶段，2000国际单位/天和4000国际单位/天剂量组的主要结局发生率高于1000国际单位/天剂量组，1000国际单位/天剂量组被选为最佳剂量（成为最佳剂量的后验概率为0.90）。在验证阶段，接受过最佳剂量的参与者（事件和观察时间仅限于他们接受1000国际单位/天的时间段；n = 308）和被随机分配接受200国际单位/天的参与者（n = 339）之间的事件发生率无显著差异（风险比[HR]，0.94[95%CI，0.76至1.15]；P = 0.54）。对伴有不良结局的跌倒分析表明，最佳剂量组比200国际单位/天组的风险更高（严重跌倒：HR，1.87[CI，1.03至3.41]；因跌倒住院：HR，2.48[CI，1.13至5.
