Clinical Trial Service Unit and Epidemiological Studies Unit, Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom.
Chinese Academy of Sciences Key Laboratory of Nutrition, Metabolism, and Food Safety, Shanghai Institute of Nutrition and Health, Chinese Academy of Sciences and University of the Chinese Academy of Sciences, Shanghai, China.
JAMA Netw Open. 2019 Dec 2;2(12):e1917789. doi: 10.1001/jamanetworkopen.2019.17789.
Vitamin D and calcium supplements are recommended for the prevention of fracture, but previous randomized clinical trials (RCTs) have reported conflicting results, with uncertainty about optimal doses and regimens for supplementation and their overall effectiveness.
To assess the risks of fracture associated with differences in concentrations of 25-hydroxyvitamin D (25[OH]D) in observational studies and the risks of fracture associated with supplementation with vitamin D alone or in combination with calcium in RCTs.
PubMed, EMBASE, Cochrane Library, and other RCT databases were searched from database inception until December 31, 2018. Searches were performed between July 2018 and December 2018.
Observational studies involving at least 200 fracture cases and RCTs enrolling at least 500 participants and reporting at least 10 incident fractures were included. Randomized clinical trials compared vitamin D or vitamin D and calcium with control.
Two researchers independently extracted data according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines and assessed possible bias. Rate ratios (RRs) were estimated using fixed-effects meta-analysis. Data extraction and synthesis took place between July 2018 and June 2019.
Any fracture and hip fracture.
In a meta-analysis of 11 observational studies (39 141 participants, 6278 fractures, 2367 hip fractures), each increase of 10.0 ng/mL (ie, 25 nmol/L) in 25 (OH)D concentration was associated with an adjusted RR for any fracture of 0.93 (95% CI, 0.89-0.96) and an adjusted RR for hip fracture of 0.80 (95% CI, 0.75-0.86). A meta-analysis of 11 RCTs (34 243 participants, 2843 fractures, 740 hip fractures) of vitamin D supplementation alone (daily or intermittent dose of 400-30 000 IU, yielding a median difference in 25[OH]D concentration of 8.4 ng/mL) did not find a reduced risk of any fracture (RR, 1.06; 95% CI, 0.98-1.14) or hip fracture (RR, 1.14; 95% CI, 0.98-1.32), but these trials were constrained by infrequent intermittent dosing, low daily doses of vitamin D, or an inadequate number of participants. In contrast, a meta-analysis of 6 RCTs (49 282 participants, 5449 fractures, 730 hip fractures) of combined supplementation with vitamin D (daily doses of 400-800 IU, yielding a median difference in 25[OH]D concentration of 9.2 ng/mL) and calcium (daily doses of 1000-1200 mg) found a 6% reduced risk of any fracture (RR, 0.94; 95% CI, 0.89-0.99) and a 16% reduced risk of hip fracture (RR, 0.84; 95% CI, 0.72-0.97).
In this systematic review and meta-analysis, neither intermittent nor daily dosing with standard doses of vitamin D alone was associated with reduced risk of fracture, but daily supplementation with both vitamin D and calcium was a more promising strategy.
维生素 D 和钙补充剂被推荐用于预防骨折，但以前的随机临床试验（RCT）报告了相互矛盾的结果，对于补充剂的最佳剂量和方案以及它们的整体效果存在不确定性。
评估 25-羟维生素 D（25[OH]D）浓度差异与观察性研究中骨折风险的关系，以及单独补充维生素 D 或同时补充维生素 D 和钙与 RCT 中骨折风险的关系。
从数据库成立到 2018 年 12 月 31 日，在 PubMed、EMBASE、Cochrane 图书馆和其他 RCT 数据库中进行了检索。检索于 2018 年 7 月至 2018 年 12 月进行。
纳入了至少 200 例骨折病例的观察性研究和至少纳入 500 名参与者且报告至少 10 例骨折的 RCT，比较了维生素 D 或维生素 D 和钙与对照组的效果。
两位研究人员根据系统评价和荟萃分析的首选报告项目（PRISMA）指南独立提取数据，并评估了可能的偏倚。使用固定效应荟萃分析估计率比（RR）。数据提取和综合于 2018 年 7 月至 2019 年 6 月进行。
任何部位骨折和髋部骨折。
在对 11 项观察性研究（39141 名参与者，6278 例骨折，2367 例髋部骨折）的荟萃分析中，25（OH）D 浓度每增加 10.0ng/ml（即 25nmol/L），调整后的任何部位骨折 RR 为 0.93（95%CI，0.89-0.96），髋部骨折 RR 为 0.80（95%CI，0.75-0.86）。对 11 项单独补充维生素 D 的 RCT（34243 名参与者，2843 例骨折，740 例髋部骨折）的荟萃分析（每日或间歇剂量为 400-30000IU，25（OH）D 浓度中位数差异为 8.4ng/ml）发现，任何部位骨折风险（RR，1.06；95%CI，0.98-1.14）或髋部骨折风险（RR，1.14；95%CI，0.98-1.32）均无降低，但这些试验受到间歇性低剂量、维生素 D 日剂量低或参与者数量不足的限制。相比之下，对 6 项 RCT（49282 名参与者，5449 例骨折，730 例髋部骨折）的荟萃分析发现，联合补充维生素 D（每日剂量为 400-800IU，25（OH）D 浓度中位数差异为 9.2ng/ml）和钙（每日剂量为 1000-1200mg）可降低 6%的任何部位骨折风险（RR，0.94；95%CI，0.89-0.99）和 16%的髋部骨折风险（RR，0.84；95%CI，0.72-0.97）。
在这项系统评价和荟萃分析中，单独使用标准剂量的维生素 D 进行间歇性或每日给药均与骨折风险降低无关，但每日同时补充维生素 D 和钙可能是一种更有前途的策略。
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