一年一次的維他命D劑量與年長婦女跌倒及骨折風險增加有關
作者：Laurie Barclay, MD
出處：WebMD醫學新聞
May 12, 2010 — 根據發表於5月12日美國醫學會期刊(Journal of the American Medical Association)的一個雙盲安慰劑控制試驗，年長、居住於社區、每年接受高劑量cholecalciferol的婦女，跌倒和骨折的風險增加。
墨爾本大學的Kerrie M. Sanders博士等人寫道，改善維他命D狀態是減少跌倒和骨折風險的一個重要調控因素；不過，根據每日補充建議量一般是不夠的，我們假設：每年給予居住於社區的年長婦女口服一次高劑量cholecalciferol (500 000 IU) 可以減少跌倒與骨折。
從2003年6月至2005年6月，共納入2,256名居住於社區的70歲以上、被視為骨折高風險的婦女，且隨機分派接受cholecalciferol (500,000 IU)或安慰劑，在每年秋冬之際給藥，為期3到5年，直到2008年研究結束。
以月曆紀錄跌倒與骨折事件，以電訪和X光檢查確認細節。對隨機抽選的137名研究對象定期抽血檢驗25-hydroxycholecalciferol和副甲狀腺荷爾蒙。
Cholecalciferol (維他命D)組有171名婦女發生骨折，安慰劑組有135人發生，骨折發生率比率(RR)為1.26 (95%信心區間[CI]為1.00 - 1.59; P = .047)，維他命D組的每100人-年骨折比率為4.9，安慰劑組為3.9。
在維他命D組中，837名婦女有2,892例跌倒事件(每100人-年比率為83.4)，安慰劑組為769人中有2,512例跌倒(每100人-年比率為72.7；發生率RR為1.15；95% CI為1.02 - 1.30；P = .03)。跌倒的事後分析發現一個暫時模式，在給藥後最初3個月，維他命D組的跌倒發生率RR相較於安慰劑組為1.31，之後9個月為1.13 (同質性檢測；P = .02)。
在抽血檢驗的病患中，血清25-hydroxycholecalciferol值中位數為49 nmol/L，這些病患不到3%的血清25-hydroxycholecalciferol值小於25 nmol/L。在維他命D組中，25-hydroxycholecalciferol值在給藥後1個月增加到約120 nmol/L，3個月時將近90 nmol/L，在給藥後12個月時依舊比安慰劑組高。
研究作者們寫道，在年長的社區居民中，一年一次給予口服高劑量cholecalciferol導致跌倒與骨折風險增加，我們的研究使用的是任何大型隨機控制試驗中最大的年度維他命D劑量(500 000 IU)，增加了劑量相關副作用的可能性。
研究限制包括，可能忽略非臨床性的脊椎骨折、可能忽略開始時的臨床資訊，因為研究對象在納入研究時並未被評估，缺乏所有病患的生化評估。
波士頓Tufts大學的Bess Dawson-Hughes醫師和Susan S. Harris醫師在編輯評論中指出，需要對基本的維他命D生理學有更佳的瞭解。
Dawson-Hughes醫師和Harris醫師寫道，特別的是，劑量大小的效果、給藥途徑(肌肉注射或口服)、給藥間隔等，對於維他命D的代謝(包括CYP24活性與局部組織特定1,25-dihydroxyvitamin D值與活性)須加以研究，也須再度評估目前提供高劑量cholecalciferol給維他命D缺乏病患之臨床實務的風險與利益，同時，重點在於重申，雖然維他命D不足很普遍，但是可以用現有的各種補充品和處方來調整，在臨床實務方面，應繼續檢視並治療。
國家健康與醫學研究委員會、澳洲政府健康與老化部支持本研究。研究作者與編輯皆宣告沒有相關財務關係。
Annual Vitamin D Dose Linked to Increased Fall, Fracture Risk in Older Women
By Laurie Barclay, MD
Medscape Medical News
May 12, 2010 — Older, community-dwelling women who receive annual oral high-dose cholecalciferol have an increased risk for falls and fractures, according to the results of a double-blind, placebo-controlled trial reported in the May 12 issue of the Journal of the American Medical Association.
"Improving vitamin D status may be an important modifiable risk factor to reduce falls and fractures; however, adherence to daily supplementation is typically poor," write Kerrie M. Sanders, PhD, from the University of Melbourne in Geelong, Australia, and colleagues. "We hypothesized that high-dose cholecalciferol (500 000 IU) given orally once a year to community-dwelling older women would reduce falls and fractures."
From June 2003 to June 2005, a total of 2256 community-dwelling women, 70 years or older, thought to be at high risk for fracture were recruited and were randomly assigned to receive cholecalciferol (500,000 IU) or placebo each autumn to winter for 3 to 5 years until study conclusion in 2008.
Monthly calendars were used to identify falls and fractures, and telephone interview and radiography allowed confirmation of the details. Serial blood sampling for 25-hydroxycholecalciferol and parathyroid hormone levels was performed in a substudy of 137 randomly selected participants.
Fractures occurred in 171 women in the cholecalciferol (vitamin D) group and in 135 in the placebo group, yielding an incidence rate ratio (RR) for fracture of 1.26 (95% confidence interval [CI], 1.00 - 1.59; P = .047). Fracture rates per 100 person-years were 4.9 for vitamin D vs 3.9 for placebo.
In the vitamin D group, there were 2892 falls in 837 women (rate, 83.4 per 100 person-years) vs 2512 falls in 769 women in the placebo group (rate, 72.7 per 100 person-years; incidence RR, 1.15; 95% CI, 1.02 - 1.30; P = .03). A post hoc analysis of falls revealed a temporal pattern, with an incidence RR of falling in the vitamin D group vs the placebo group of 1.31 in the first 3 months after dosing and 1.13 during the following 9 months (test for homogeneity; P = .02).
Median baseline serum 25-hydroxycholecalciferol level was 49 nmol/L in participants in the substudy, and less than 3% of the substudy participants had 25-hydroxycholecalciferol levels of less than 25 nmol/L. In the vitamin D group, 25-hydroxycholecalciferol levels increased to approximately 120 nmol/L at 1 month after dosing, were approximately 90 nmol/L at 3 months, and remained higher than the placebo group at 12 months after dosing.
"Among older community-dwelling women, annual oral administration of high-dose cholecalciferol resulted in an increased risk of falls and fractures," the study authors write. "Our study used the largest total annual dose of vitamin D (500 000 IU) reported in any large randomized controlled trial, raising the possibility that the adverse outcome is dose-related."
Limitations of this study include the possibility that nonclinical vertebral fractures would have been missed, possibly missing baseline clinical information because the participants were not evaluated at the study center, and lack of biochemical assessment of all participants.
In an accompanying editorial, Bess Dawson-Hughes, MD, and Susan S. Harris, DSc, from Tufts University in Boston, Massachusetts, note the need for better understanding of basic vitamin D physiology.
"Specifically, the effect of dose size, route (intramuscular vs. oral), and dosing interval on aspects of vitamin D metabolism including CYP24 activity and on local tissue-specific 1,25-dihydroxyvitamin D levels and actions should be investigated," Drs. Dawson-Hughes and Harris write. "It may also be necessary to reevaluate the risks and benefits of the current clinical practice of providing high loading doses of cholecalciferol to patients who are vitamin D deficient. In the meantime, it is important to reiterate that although vitamin D insufficiency is widespread, it can be safely corrected with a variety of existing supplement types and regimens and it should continue to be identified and treated in clinical practice."
The National Health and Medical Research Council and the Australian Government Department of Health and Ageing supported this study. The study authors and editorialists have disclosed no relevant financial relationships.
JAMA. 2010;303:1815-1822, 1861-1862.
