Mellanby Centre for Musculoskeletal Research, University of Sheffield, Northern General Hospital, Sheffield, UK.
School of Health and Related Research, University of Sheffield, Sheffield, UK.
Lancet Healthy Longev. 2021 Apr;2(4):e212-e221. doi: 10.1016/S2666-7568(21)00051-9.
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.
观察性研究和临床前研究表明，硒状态、骨骼健康和身体功能之间存在关联。欧洲大多数成年人的血清硒含量处于最佳范围以下。我们假设硒补充剂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。
我们完成了一项为期 6 个月的随机、双盲、安慰剂对照试验。我们招募了英国谢菲尔德北方总医院年龄在 55 岁以上的绝经后妇女，这些妇女患有骨量减少或骨质疏松症。参与者被随机分为 1:1:1 组，分别接受亚硒酸钠 200μg、50μg 或安慰剂，每日口服一次。药物由站点以盲法和编号的方式提供，采用 18 个单位的分组随机序列，参与者按数字顺序分配药物。所有参与者和研究团队都对治疗分配进行了盲法。主要终点是 26 周时尿Ⅰ型胶原 N 末端交联肽（NTx，以肌酐比值表示）。分析包括所有完成随访的随机分配参与者。采用协方差分析和 Hochberg 检验比较各组。次要终点是其他骨转换生化标志物、骨密度、短体性能电池和握力。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。这项试验在欧盟临床试验（EudraCT 2016-002964-15）和临床试验.gov（NCT02832648）进行了注册，现已完成。
2017 年 1 月 23 日至 2018 年 4 月 11 日期间，我们招募了 120 名参与者，并随机分为亚硒酸钠 200μg、50μg 或安慰剂组（每组 40 名）。120 名参与者中有 115 名（96%）完成了随访并纳入主要分析（200μg 组[n=39]、50μg 组[n=39]、安慰剂组[n=37]）。中位随访时间为 25.0 周（IQR 24.7-26.0）。在 200μg 组中，血清硒水平从 78.8（95%CI 73.5-84.2）增加到 105.7μg/L（99.5-111.9）。26 周时，尿 NTx 与肌酐比值（nmol 骨胶原当量：mmol 肌酐）在治疗组之间无显著差异：安慰剂组为 40.5（95%CI 34.9-47.0），50μg 组为 43.4（37.4-50.5），200μg 组为 42.2（37.5-47.6）。26 周时，次要终点或机制终点测量值在治疗组之间无差异。由于甲状腺刺激激素浓度异常（200μg 组 1 例，50μg 组 3 例，安慰剂组 3 例）和血糖异常（50μg 组 1 例），120 名参与者中有 7 名（6%）在第 13 周退出治疗。有 3 例严重不良事件：第 18 周发生非 ST 段抬高型心肌梗死（50μg 组），第 2 周常规人群筛查后诊断为结肠癌（安慰剂组），第 4 周因转移性结肠癌发生肺栓塞（200μg 组）。主要研究者均认为所有严重不良事件与试验药物无关。
在这些剂量下，硒补充剂不会影响绝经后妇女的骨骼肌肉健康。
英国国家卫生研究院疗效和机制评价计划。
