观察性和临床前研究表明硒状态之间的关联,骨骼健康,和身体功能。欧洲大多数成年人的血清硒含量低于最佳范围。我们假设补充硒可以减少活性氧对破骨细胞的促吸收作用并改善身体功能。
我们完成了为期6个月的随机调查,双盲,安慰剂对照试验。我们在北方总医院招募了年龄超过55岁的骨质减少或骨质疏松症的绝经后妇女,谢菲尔德,英国。参与者被随机分配1:1:1接受亚硒酸盐200μg,50μg,或安慰剂每天口服一次。将药物提供给盲化的位点,并通过区块大小为18的区块随机序列进行编号,并按数字顺序为参与者分配药物。所有参与者和研究小组都被掩盖了治疗分配。主要终点是I型胶原蛋白的尿液N末端交联端肽(NTx,以与肌酐的比率表示)在26周。分析包括完成随访的所有随机分配的参与者。通过Hochberg检验的协方差分析比较各组。次要终点是骨转换的其他生化标志物,骨矿物质密度,短物理性能电池,和握力。机制终点是谷胱甘肽过氧化物酶,高敏C反应蛋白,和白细胞介素-6.该试验已在欧盟临床试验中注册,EudraCT2016-002964-15和ClinicalTrials.gov,NCT02832648,完成。
在2017年1月23日至2018年4月11日之间招募了120名参与者,并随机分配给亚硒酸盐200μg,50μg,或安慰剂(每组n=40)。120名参与者中有115名(96%)完成了随访,并纳入了主要分析(200μg[n=39],50μg[n=39],安慰剂[n=37])。中位随访时间为25·0周(IQR24·7-26·0)。在200μg组中,平均血清硒从78·8(95%CI73·5-84·2)增加到105·7μg/L(99·5-111·9)。在26周时,治疗组之间的尿液NTx与肌酐之比(nmol骨胶原当量:mmol肌酐)没有显着差异:安慰剂组40·5(95%CI34·9-47·0),43·4(37·4-50·5)为50μg,和42·2(37·5-47·6)为200μg。在26周时,治疗组之间的次要或机械终点测量均无差异。在第13周,120名参与者中有7名(6%)因促甲状腺激素浓度异常而退出治疗(200μg组中有一名,50μg组中有三个,安慰剂组3例)和异常血糖(50μg组1例)。有三个严重不良事件:18周时的非ST段抬高型心肌梗死(50μg组),在第2周进行常规人群筛查后诊断为肠癌(安慰剂组),和第4周因转移性肠癌引起的肺栓塞(200μg组)。主要研究者判断所有严重不良事件与试验药物无关。
这些剂量的硒补充不会影响绝经后妇女的肌肉骨骼健康。
英国国家卫生研究所功效和机制评估计划。
Observational and preclinical studies show associations between selenium status, bone health, and physical function. Most adults in Europe have serum selenium below the optimum range. We hypothesised that selenium supplementation could reduce pro-resorptive actions of reactive oxygen species on osteoclasts and improve physical function.
We completed a 6-month randomised, double-blind, placebo-controlled
trial. We recruited postmenopausal women older than 55 years with osteopenia or osteoporosis at the Northern General Hospital, Sheffield, UK. Participants were randomly assigned 1:1:1 to receive selenite 200 μg, 50 μg, or placebo orally once per day. Medication was supplied to the site blinded and numbered by a block randomisation sequence with a block size of 18, and participants were allocated medication in numerical order. All participants and
study team were masked to treatment allocation. The primary endpoint was urine N-terminal cross-linking telopeptide of type I collagen (NTx, expressed as ratio to creatinine) at 26 weeks. Analysis included all randomly assigned participants who completed follow-up. Groups were compared with analysis of covariance with Hochberg testing. Secondary endpoints were other biochemical markers of bone turnover, bone mineral density, short physical performance battery, and grip strength. Mechanistic endpoints were glutathione peroxidase, highly sensitive C-reactive protein, and interleukin-6. This
trial is registered with EU clinical trials, EudraCT 2016-002964-15, and ClinicalTrials.gov, NCT02832648, and is complete.
120 participants were recruited between Jan 23, 2017, and April 11, 2018, and randomly assigned to selenite 200 μg, 50 μg, or placebo (n=40 per group). 115 (96%) of 120 participants completed follow-up and were included in the primary analysis (200 μg [n=39], 50 μg [n=39], placebo [n=37]). Median follow-up was 25·0 weeks (IQR 24·7-26·0). In the 200 μg group, mean serum selenium increased from 78·8 (95% CI 73·5-84·2) to 105·7 μg/L (99·5-111·9). Urine NTx to creatinine ratio (nmol bone collagen equivalent:mmol creatinine) did not differ significantly between treatment groups at 26 weeks: 40·5 (95% CI 34·9-47·0) for placebo, 43·4 (37·4-50·5) for 50 μg, and 42·2 (37·5-47·6) for 200 μg. None of the secondary or mechanistic endpoint measurements differed between treatment groups at 26 weeks. Seven (6%) of 120 participants were withdrawn from treatment at week 13 due to abnormal thyroid-stimulating hormone concentrations (one in the 200 μg group, three in the 50 μg group, and three in the placebo group) and abnormal blood glucose (one in the 50 μg group). There were three serious adverse events: a non-ST elevation myocardial infarction at week 18 (in the 50 μg group), a diagnosis of bowel cancer after routine population screening at week 2 (in the placebo group), and a pulmonary embolus due to metastatic bowel cancer at week 4 (in the 200 μg group). All severe adverse events were judged by the principal investigator as unrelated to
trial medication.
Selenium supplementation at these doses does not affect musculoskeletal health in postmenopausal women.
UK National Institute for Health Research Efficacy and Mechanism Evaluation programme.