Effect of selenium supplementation on musculoskeletal health in older women: a randomised, double-blind, placebo-controlled trial

Abstract

Background: 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.

Methods: 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.

Findings: 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.

Interpretation: Selenium supplementation at these doses does not affect musculoskeletal health in postmenopausal women.

Funding: UK National Institute for Health Research Efficacy and Mechanism Evaluation programme.

Conflict of interest statement

JSW declares grants from the NIHR during the conduct of the study; and personal fees from Mereo and Sandoz, personal fees and non-financial support from Eli Lilly, grants from Alexion, and non-financial support from Consilient, outside the submitted work. RMJ declares grants from the NIHR during the conduct of the study. LS declares shares in selenOmed, outside the submitted work. TRH declares speaker fees from DSM, outside the submitted work. JCM declares grants from the NIHR during the conduct of the study. RE declares grants from Amgen, Alexion, and Roche; grants and personal fees from IDS; personal fees from GSK Nutrition, Mereo, Sandoz, AbbiVie, Samsung, Haoma Medica, Elsevier, CL Bio, the Foundation for the National Institutes of Health, Viking, the University of California San Francisco, Biocon, and Lyramid; and grants and personal fees from Nittobo, outside the submitted work. GRW declares no competing interests.

© 2021 The Authors. Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license.

Figures

Figure

Trial profile The number of participants included in the per-protocol analysis differs from the per-protocol NTx results table (appendix p 2) due to missing NTx measurements. AE=adverse event. BMD=bone mineral density. NTx=N-terminal cross-linking telopeptide of type I collagen. TSH=thyroid-stimulating hormone.