维生素D摄入量够大才能降低骨折风险

《新英格兰医学杂志》7月4日在线发表的一项最新Meta分析显示，只有摄入大剂量的维生素D补充剂(≥800 IU/d)才能降低老年人的骨折风险。65岁以上老年人摄入大剂量补充剂可使髋关节骨折风险降低30%，非椎体骨折风险降低14%(N. Engl. J. Med. 2012 July 4 [doi: 10.1056/NEJMoa1109617])。

既往许多探讨维生素D补充剂保护作用的临床研究及其Meta分析得出了明显相互矛盾的结果，有些发现骨折风险降低达20％，有些则未发现获益，而有些甚至发现了对骨折风险的负面影响。

苏黎世大学衰老与活动中心的Heike A. Bischoff-Ferrari及其同事推测，这些临床研究及Meta分析很多存在两方面缺陷，一是依赖于分析处方的维生素D剂量而非实际服用的剂量，二是未考虑受试者的基线25-羟基维生素D水平，后者是评价维生素D缺乏程度的指标。

本项Meta分析中仅纳入记录受试者的口服维生素D补充剂实际摄入量或校正受试者对处方补充剂的依从性的双盲随机对照研究。因此，最后这项Meta分析仅能够纳入11项研究，共涉及31,022例受试者。

评价处方补充剂的意向治疗分析显示，髋关节骨折风险降低10%，降幅不显著。然而，对受试者的实际维生素D补充剂摄入量进行比较发现，最高摄入量(800~2,000 IU/d)组的髋关节骨折风险显著降低30%。值得注意的是，实际摄入量低于792 IU/d的受试者的髋关节骨折风险未降低。同样，意向治疗分析显示，非椎体骨折的风险降低7%，降幅不显著，而对实际摄入量的比较显示，最高摄入量组的风险显著降低14%。

内部验证分析显示维生素D实际摄入量与骨折风险之间存在量效关系，支持上述结果。一些敏感性分析显示维生素D补充剂对一些患者亚组(包括所有年龄和性别)也有益，同样支持上述结果。

既往Meta分析表明维生素D的获益仅限于居住于疗养机构的老年人，但本文作者进行的亚组分析表明，在最高实际摄入量水平，所有65岁以上老年人的髋关节骨折风险均降低，不管是居住于社区还是疗养机构。

作者还发现，最易出现维生素D缺乏者(85岁以上者和基线25-羟基维生素D水平极低者)从维生素D补充剂获得的益处至少与其他人一样多。

总体而言，上述Meta分析结果支持美国医学研究所的建议，即65岁以上老年人应每天服用800 IU维生素D。另外，该分析结果提示，既往一些高质量的维生素D补充剂研究要么是因为维生素D剂量低于预定剂量而未观察到获益，要么是因为剂量高于预定剂量而观察到意外获益。

该Meta分析获瑞士国家基金会等机构支持。研究者与帝斯曼营养产品部等公司存在联系。

爱思唯尔  版权所有

By: MARY ANN MOON, Internal Medicine News Digital Network

Only high intake of vitamin D supplementation with 800 IU or more per day appears to reduce the risk of fracture significantly in the elderly, according to the latest meta-analysis on the subject reported online July 4 in the New England Journal of Medicine.

Such high levels of supplementation appear to reduce the risk of hip fracture by 30% and the risk of nonvertebral fracture by 14% in people aged 65 years and older, said Dr. Heike A. Bischoff-Ferrari, of the Center on Aging and Mobility at the University of Zurich, and her associates.

Many previous meta-analyses of the protective effect of vitamin D supplements, like the numerous clinical trials they reviewed, have produced markedly conflicting results. Some have found reductions in fracture risk of up to 20%, others have found no beneficial effect, and a few have even found negative effects on fracture risk.

Dr. Bischoff-Ferrari and her colleagues reasoned that many of these clinical trials, as well as the meta-analyses that pooled their findings, were flawed by relying on the doses of vitamin D that were prescribed for subjects rather than the actual amount that subjects took. Many also were flawed in that they did not take into account subjects’ baseline levels of 25-hydroxyvitamin D, an indicator of the degree of their vitamin D deficiency.

So for their meta-analysis, the investigators included only double-blind, randomized, controlled trials that either recorded subjects’ actual intake of oral vitamin D supplements or controlled for their adherence to prescribed supplementation. Thus, the investigators were able to include only 11 studies, with a pooled population of 31,022 subjects, in their meta-analysis.

The intention-to-treat analysis, which examined the prescribed supplementation, showed a nonsignificant 10% reduction in the risk of hip fracture. However, a comparison of subjects’ actual intake of vitamin D supplements showed a significant 30% reduction in risk of hip fracture at the highest levels of intake (800-2,000 IU daily).

"Notably, there was no reduction in risk of hip fracture at any actual intake level lower than 792 IU per day," Dr. Bischoff-Ferrari and her associates said (N. Engl. J. Med. 2012 July 4 [doi: 10.1056/NEJMoa1109617]).

Similarly, the intention-to-treat analysis showed a nonsignificant 7% reduction in the risk of nonvertebral fracture, while a comparison of actual intake levels showed a significant 14% decline in risk at the highest levels of intake.

Internal validation analyses supported these results, and indicated that there was a dose-response relationship between vitamin D dose actually ingested and fracture risk. Several sensitivity analyses also bolstered the findings, and showed that the benefit of vitamin D supplements extended across several subgroups of patients, including all ages and both sexes.

"Previous meta-analyses have suggested that the benefits of vitamin D may be limited to older persons who live in institutions. Our subgroup analyses suggest that at the highest actual intake level, the risk of hip fracture is reduced among all persons 65 years of age or older, whether they live in the community or in an institution.

"Our data further suggest that persons who are most vulnerable to vitamin D deficiency – those 85 years of age or older and those with very low baseline levels of 25-hydroxyvitamin D – benefit from vitamin D supplementation at least as much as others do," they added.

Overall, the study results support the Institute of Medicine’s recommendation that people aged 65 years and older receive 800 IU of vitamin D each day, the investigators noted.

In addition, "our findings suggest that some previous high-quality trials of vitamin D supplementation either showed no benefit owing to lower-than-intended doses of vitamin D or showed an unexpected benefit owing to higher-than-intended doses," they said.

This study was supported by the Swiss National Foundation, the European Commission Framework 7 Program, and DSM Nutritional Products. Dr. Bischoff-Ferrari reported ties to DSM Nutritional Products, Amgen, MSD, Novartis, Roche, and Nestle, and her associates reported ties to numerous industry sources.