Population Health Program, QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia.
Department of Medicine, School of Clinical Sciences, Monash University, Melbourne, VIC, Australia.
Lancet Diabetes Endocrinol. 2023 May;11(5):324-332. doi: 10.1016/S2213-8587(23)00063-3. Epub 2023 Mar 31.
Low serum 25-hydroxy vitamin D concentration is associated with increased fracture risk. It is uncertain whether vitamin D supplementation reduces fractures, or whether intermittent doses are harmful. We aimed to investigate if supplementing adults living in Australia with monthly doses of 60 000 international units (IU) vitamin D for 5 years or less altered the rate of fractures.
We did a population-based, double-blind, randomised, placebo-controlled trial of oral vitamin D supplementation (60 000 IU per month) for up to 5 years in adults aged 60-84 years living in Australia. We randomly assigned (1:1) 21 315 participants to either vitamin D or placebo. We ascertained fractures through linkage with administrative datasets. The main outcome was total fractures. Additional outcomes were non-vertebral, major osteoporotic (hip, wrist, proximal humerus, and spine), and hip fractures. We excluded participants (989 [4·6%]) without linked data, and estimated hazard ratios (HRs) and 95% CIs using flexible parametric survival models. The trial is registered with the Australian New Zealand Clinical Trials Registry, ACTRN12613000743763, and the trial intervention ended in February, 2020.
Between Feb 14, 2014, and June 17, 2015, we recruited 21 315 participants. For the current analysis, we included 20 326 participants (vitamin D 10 154 [50·0%]; placebo 10 172 [50·0%]). 9295 (45·7%) of 20 326 participants were women and the mean age was 69·3 years (SD 5·5). Over a median follow-up of 5·1 years (IQR 5·1-5·1), 568 (5·6%) participants in the vitamin D group and 603 (5·9%) in the placebo group had one or more fractures. There was no effect on fracture risk overall (HR 0·94 [95% CI 0·84-1·06]), and the interaction between randomisation group and time was not significant (p=0·14). However, the HR for total fractures appeared to decrease with increasing follow-up time. The overall HRs for non-vertebral, major osteoporotic, and hip fractures were 0·96 (95% CI 0·85-1·08), 1·00 (0·85-1·18), and 1·11 (0·86-1·45), respectively.
These findings do not support concerns that bolus doses of vitamin D administered monthly increase fracture risk. Long-term supplementation might reduce the incidence of total fractures, but additional research is needed to clarify this effect.
Australian National Health and Medical Research Council.
血清 25-羟维生素 D 浓度低与骨折风险增加有关。目前尚不确定维生素 D 补充剂是否能降低骨折风险，或者间歇性剂量是否有害。我们旨在研究澳大利亚成年人每月服用 60000 国际单位（IU）维生素 D 5 年或更短时间是否会改变骨折发生率。
我们进行了一项基于人群的、双盲、随机、安慰剂对照试验，对澳大利亚 60-84 岁的成年人进行为期 5 年的口服维生素 D 补充（每月 60000IU）。我们将 21315 名参与者随机分配（1:1）至维生素 D 组或安慰剂组。我们通过与行政数据集的联系来确定骨折情况。主要结局是总骨折。其他结局是非椎体、主要骨质疏松性（髋部、腕部、肱骨近端和脊柱）和髋部骨折。我们排除了没有相关数据的参与者（989 [4.6%]），并使用灵活参数生存模型估计了危险比（HR）和 95%CI。该试验在澳大利亚和新西兰临床试验注册处注册，ACTRN12613000743763，试验干预于 2020 年 2 月结束。
2014 年 2 月 14 日至 2015 年 6 月 17 日期间，我们招募了 21315 名参与者。对于本次分析，我们纳入了 20326 名参与者（维生素 D 组 10154 [50.0%]；安慰剂组 10172 [50.0%]）。20326 名参与者中有 9295 名（45.7%）为女性，平均年龄为 69.3 岁（标准差 5.5）。中位随访时间为 5.1 年（IQR 5.1-5.1），维生素 D 组有 568 名（5.6%）参与者和安慰剂组有 603 名（5.9%）参与者发生了 1 次或多次骨折。总体骨折风险无显著影响（HR 0.94 [95%CI 0.84-1.06]），随机分组与时间之间的交互作用也不显著（p=0.14）。然而，总骨折的 HR 似乎随随访时间的增加而降低。非椎体、主要骨质疏松性和髋部骨折的总体 HR 分别为 0.96（95%CI 0.85-1.08）、1.00（95%CI 0.85-1.18）和 1.11（95%CI 0.86-1.45）。
这些发现并不支持每月给予大剂量维生素 D 会增加骨折风险的担忧。长期补充可能会降低总骨折的发生率，但需要进一步研究来明确这种效果。
澳大利亚国家卫生和医学研究委员会。
