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

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

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

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

Long‐term selenium‐yeast supplementation does not affect bone turnover markers: a randomized placebo‐controlled trial

Higher selenium status has been associated with lower bone turnover markers (BTM) in epidemiological studies. However, the long-term impact of selenium supplementation on BTMs has not been studied. We investigated the effects of selenium supplementation on BTMs including osteocalcin (OC), procollagen type I N-terminal propeptide (PINP), collagen type I cross-linked C-telopeptide (CTX), and bone alkaline phosphatase (BALP) in the short (6 months) and long term (5 years). A total of 481 Danish men and women (60–74 years) were randomized to receive placebo-yeast versus 100, 200, or 300 μg selenium as selenium-enriched yeast daily for 5 years. Plasma selenium concentration was measured using inductively coupled plasma mass spectrometry, and BTMs were measured in nonfasted samples at baseline, 6 months, and 5 years. Data were analyzed by ANCOVA to investigate the shape of the dose-response relationships. Covariates included age, body mass index, baseline selenium status, baseline BTM, smoking, alcohol, supplement use, and medication. Plasma selenium concentration (mean 86.5 μg/d at baseline) increased significantly with increasing selenium supplementation to 152.6, 209.1, and 253.7 μg/L after 6 months and remained elevated at 5 years (158.4, 222.4, and 275.9 μg/L for 100, 200, and 300 μg supplemental selenium/d, respectively (p < 0.001)). There was no change in plasma selenium concentration in the placebo-treated group. There was no significant effect of selenium supplementation on OC (6 months p = 0.37; 5 years p = 0.63), PINP (6 months p = 0.37; 5 years p = 0.79), CTX (6 months p = 0.91; 5 years p = 0.58) or BALP (6 months p = 0.17; 5 years p = 0.53). The relatively replete baseline selenium status in the study participants may explain this lack of effect. Testing in more deficient populations may provide further insights into the impact of selenium supplementation on bone health. © 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR)

Selenium status and its determinants in very old adults: insights from the Newcastle 85+ Study

There is a dearth of data on Se status in very old adults. The aims of this study were to assess Se status and its determinants in 85-year-olds living in the Northeast of England by measuring serum Se and selenoprotein P (SELENOP) concentrations and glutathione peroxidase 3 (GPx3) activity. A secondary aim was to examine the interrelationships between each of the biomarkers. In total, 757 participants (463 women, 293 men) from the Newcastle 85+ Study were included. Biomarker concentrations were compared with selected cut-offs (serum Se: suboptimal 70 µg/l and deficient 45 µg/l; SELENOP: suboptimal 4·5 mg/l and deficient 2·6 mg/l). Determinants were assessed using linear regressions, and interrelationships were assessed using restricted cubic splines. Median (inter-quartile range) concentrations of serum Se, SELENOP and of GPx3 activity were 53·6 (23·6) µg/l, 2·9 (1·9) mg/l and 142·1 (50·7) U/l, respectively. Eighty-two percentage and 83 % of participants had suboptimal serum Se (< 70 µg/l) and SELENOP (< 4·5 mg/l), and 31 % and 40 % of participants had deficient serum Se (< 45 µg/l) and SELENOP (< 2·6 mg/l), respectively. Protein intake was a significant determinant of Se status. Additional determinants of serum Se were sex, waist:hip ratio, self-rated health and disease, while sex, BMI and physical activity were determinants of GPx3 activity. There was a linear association between serum Se and SELENOP, and nonlinear associations between serum Se and GPx3 activity and between SELENOP and GPx3 activity. These findings indicate that most participants had suboptimal Se status to saturate circulating SELENOP

A record of soil loss from Butrint, southern Albania, using mineral magnetism indicators and charcoal (AD 450 to 1200).

Mineral magnetic and charcoal analyses were carried out on two sections 0.6 km apart on the Vrina Plain at Shën Dëlli, a suburb of Roman Butrint (ancient Buthrotum), southern Albania. Using a chronology developed by archaeomagnetic dating, the two sections postdate Roman archaeological structures on the site, providing a sediment record between c. ad 450 and 1200. Environmental magnetic data were analysed using cluster analysis to interpret a consistent stratigraphic development between the two sections. Above the archaeo logical remains on the western side of the Shën Dëli settlement, marsh clay sedimentation started ad 450–500, contemporaneous with evidence of site occupation. Anthropogenic activity is evident from the high macro-charcoal content, which declines at ad 750–800, and may mark the end of settlement in the vicinity. Both sections show similar sedimentation rates which, when extrapolated, suggest that marsh growth to the present day levels would have been completed between about ad 1500 and 1600. From about ad 750 to 850 sedimentation continued consistently across the site, with low microcharcoal input, but an increasingly important pres ence of magnetic minerals, including superparamagnetic magnetite, associated with top soil input. Between ad 1050 and 1200 the input from magnetically enhanced topsoil had increased tenfold over 300 years earlier, indicating that soil erosion was a major sediment source. This marked increase in soil loss could be due either to different land-management practices or to local deforestation. Whether this change in topsoil loss is linked to climatic changes associated with the beginning of the ‘Mediaeval Warm Period’ (c. ad 1000–1400) needs further investigation