Ferguson Janet H, Chang Anne B
Christchurch Hospital, Canterbury District Health Board, Private Bag 4710, Christchurch, New Zealand, 8140.
Cochrane Database Syst Rev. 2014 May 14;2014(5):CD007298. doi: 10.1002/14651858.CD007298.pub4.
Cystic fibrosis (CF) is a genetic disorder with multiorgan effects. In a subgroup with pancreatic insufficiency malabsorption of the fat soluble vitamins (A, D, E, K) may occur. Vitamin D is involved in calcium homeostasis and bone mineralisation and may have extraskeletal effects. This review examines the evidence for vitamin D supplementation in cystic fibrosis.
To assess the effects of vitamin D supplementation on the frequency of vitamin D deficiency, respiratory outcomes and vitamin D toxicity in the cystic fibrosis population.
We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register comprising references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings.Date of the most recent search: 08 July 2013.
Randomised and quasi-randomised controlled studies of vitamin D supplementation compared to placebo in the cystic fibrosis population regardless of exocrine pancreatic function.
Both authors independently assessed the risk of bias of each included study and extracted outcome data (from published study information) for assessment of bone mineralization, growth and nutritional status, frequency of vitamin D deficiency, respiratory status, quality of life and adverse events.
Six studies (239 participants) are included, although only three studies provided data from 69 adults and children with cystic fibrosis for analysis. One study compared a single high dose of vitamin D (250,000 IU) to placebo at the time of hospital admission with a respiratory exacerbation in 30 pancreatic insufficient adults with cystic fibrosis. The second study compared supplemental 800 international units (IU) vitamin D and placebo for 12 months in 30 osteopenic pancreatic insufficient adults; both groups continued 900 IU vitamin D daily. The third study compared supplemental 1 g calcium alone, 1600 IU vitamin D alone, 1600 IU vitamin D and 1 g calcium and placebo in a double-blind randomised cross-over study; only nine children who completed both vitamin D and placebo groups after six-months supplementation and a three-month washout period are included; pancreatic sufficiency or disease status of participants are not defined. The studies are not directly comparable due to differences in supplementation, outcome reporting and possibly participant characteristics (e.g. severity of lung disease, growth and nutrition, pancreatic sufficiency).The only outcome for which we could combine data from more than two studies was 25-hydroxyvitamin D levels; patients receiving vitamin D supplementation had significantly higher levels, mean difference 7.24 ng/ml (95% confidence interval 5.01 to 9.46). However, ironically one study reported 1,25(OH)2D with levels significantly favouring the placebo group, mean difference -30.30 pmol/ml (95% confidence interval -59.89 to -0.71). Bone mineral density was measured in two studies; both described no significant change between groups. There were no adverse events in any study.The remaining three studies are published as abstracts only and did not provide data for analysis. These abstracts include: a report of pre-intervention data in a study comparing daily calcitriol (0.25 or 0.5 micrograms) with placebo in pancreatic insufficient children and young adults; an interim report of a double-blind randomised control study comparing 5000 IU vitamin D daily for 12 weeks during winter in 67 adult cystic fibrosis patients; and a comparison of the effect of three months of vitamin D supplementation (dose not specified) with placebo on bone mineral density in 42 children with cystic fibrosis and low bone mineral density.Risk of bias was highly variable between all studies. Only one study had a low risk of bias for the five main criteria (random sequence generation, allocation, blinding, attrition and reporting). The rest of the studies had unclear or high risks of bias. Two studies had a low risk of bias for blinding and another two studies for attrition bias. In the studies published as abstracts, assessment of the risks of bias was uncertain in many aspects.
AUTHORS' CONCLUSIONS: In patients receiving vitamin D supplementation, 25-hydroxyvitamin D levels are significantly higher. However, there is no evidence of clinical benefit or harm in the limited number of small-sized published studies. Adherence to relevant cystic fibrosis guidelines on vitamin D supplementation should be considered until further evidence is available.
囊性纤维化（CF）是一种具有多器官影响的遗传性疾病。在胰腺功能不全的亚组中，可能会出现脂溶性维生素（A、D、E、K）吸收不良。维生素D参与钙稳态和骨矿化，可能具有骨骼外效应。本综述探讨了囊性纤维化患者补充维生素D的证据。
评估补充维生素D对囊性纤维化人群维生素D缺乏频率、呼吸结局和维生素D毒性的影响。
我们检索了Cochrane囊性纤维化和遗传疾病小组试验注册库，其中包括通过全面电子数据库检索以及对相关期刊和会议论文摘要集进行手工检索而识别的参考文献。最近一次检索日期：2013年7月8日。
在囊性纤维化人群中，将补充维生素D与安慰剂进行比较的随机和半随机对照研究，无论外分泌胰腺功能如何。
两位作者独立评估了每项纳入研究的偏倚风险，并提取了结局数据（来自已发表的研究信息），以评估骨矿化、生长和营养状况、维生素D缺乏频率、呼吸状况、生活质量和不良事件。
纳入了6项研究（239名参与者），尽管只有3项研究提供了69名患有囊性纤维化的成人和儿童的数据用于分析。一项研究在30名胰腺功能不全的成年囊性纤维化患者因呼吸加重入院时，将单次高剂量维生素D（250,000 IU）与安慰剂进行比较。第二项研究在30名骨质减少的胰腺功能不全成人中，将补充800国际单位（IU）维生素D和安慰剂进行了12个月的比较；两组均继续每日补充900 IU维生素D。第三项研究在一项双盲随机交叉研究中，比较了单独补充1 g钙、单独补充1600 IU维生素D、1600 IU维生素D和1 g钙以及安慰剂；仅纳入了9名在补充6个月和3个月洗脱期后完成维生素D组和安慰剂组的儿童；未定义参与者的胰腺功能或疾病状态。由于补充方式、结局报告以及可能的参与者特征（如肺部疾病严重程度、生长和营养、胰腺功能）不同，这些研究无法直接进行比较。我们能够合并两项以上研究数据的唯一结局是25-羟维生素D水平；接受维生素D补充的患者水平显著更高，平均差异为7.24 ng/ml（95%置信区间5.01至9.46）。然而，具有讽刺意味的是，一项研究报告1,25(OH)2D水平显著有利于安慰剂组，平均差异为-30.30 pmol/ml（95%置信区间-59.89至-0.71）。两项研究测量了骨密度；两者均描述组间无显著变化。任何研究中均未出现不良事件。其余三项研究仅以摘要形式发表，未提供分析数据。这些摘要包括：一项研究的干预前数据报告，该研究比较了胰腺功能不全的儿童和年轻人中每日骨化三醇（0.25或0.5微克）与安慰剂；一项双盲随机对照研究的中期报告，该研究比较了67名成年囊性纤维化患者在冬季每日补充5000 IU维生素D持续12周的情况；以及一项比较3个月维生素D补充（剂量未指定）与安慰剂对42名骨密度低的囊性纤维化儿童骨密度影响的研究。所有研究之间的偏倚风险差异很大。只有一项研究在五个主要标准（随机序列生成、分配、盲法、失访和报告）方面偏倚风险较低。其余研究的偏倚风险不明确或较高。两项研究在盲法方面偏倚风险较低，另外两项研究在失访偏倚方面偏倚风险较低。在以摘要形式发表的研究中，偏倚风险评估在许多方面不确定。
在接受维生素D补充的患者中，25-羟维生素D水平显著更高。然而，在有限数量的小型已发表研究中，没有临床获益或危害的证据。在有更多证据之前，应考虑遵循囊性纤维化关于维生素D补充的相关指南。
