Selenium supplementation to improve bone health in postmenopausal women: the SeMS three-arm RCT

Background Observational and pre-clinical studies have reported an association between selenium status, bone density, bone turnover and fracture risk. Selenium is an anti-oxidant, so we hypothesised that selenium could reduce the pro-resorptive action of reactive oxygen species on osteoclasts. Population mortality data suggest that the optimum range for serum selenium is 120–150 µg/l. Most adults in Europe are relatively selenium insufficient compared with adults in the USA and other geographical areas. Objectives The objectives of the study were to determine if selenium supplementation in postmenopausal women with osteopenia decreased bone turnover, improved physical function or decreased markers of oxidative stress and inflammation. Design We conducted a 6-month double-blind, randomised, placebo-controlled trial. Setting This was a single-centre study in Sheffield, UK. Participants We recruited 120 postmenopausal women with osteopenia or osteoporosis. One hundred and fifteen women completed follow-up and were included in the intention-to-treat analysis. Interventions The interventions were sodium selenite as Selenase 200 µg/day, Selenase 50 µg/day (biosyn, Germany) and placebo. Main outcome measures The primary end point was urine N–terminal cross-linking telopeptide of type I collagen/Cr (NTX/Cr) at 26 weeks. Groups were compared with an analysis of covariance, through the use of Hochberg testing. Secondary end points were other biochemical markers of bone turnover, bone mineral density by dual-energy X-ray absorptiometry and physical function scores (short physical performance battery and grip strength). The mechanistic end points were markers of inflammation and anti-oxidant activity (glutathione peroxidase, highly sensitive C-reactive protein and interleukin 6). Results In the 200 µg/day group, mean serum selenium increased from 78.8 µg/l (95% confidence interval 73.5 to 84.2 µg/l) to 105.7 µg/l (95% confidence interval 99.5 to 111.9 µg/l) at 26 weeks. Urine NTX/Cr did not differ between treatment groups at 26 weeks. None of the secondary or mechanistic end-point measurements differed between the treatment groups at 26 weeks. Conclusions We conclude that selenium supplementation at these doses does not affect bone turnover (assessed by NTX/Cr) and is not beneficial for musculoskeletal health in postmenopausal women. Trial registration IRAS 200308, EudraCT 2016-002964-15 and ClinicalTrials.gov NCT02832648. Funding This project was funded by the Efficacy and Mechanism Evaluation (EME) programme, a MRC and National Institute for Health Research (NIHR) partnership. This will be published in full in Efficacy and Mechanism Evaluation; Vol. 8, No. 6. See the NIHR Journals Library website for further project information.