Selenium for Musculoskeletal Health

Study Overview
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Brief Summary
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This research aims to determine whether selenium supplements improve bone and muscle health in older women at risk of osteoporosis (low bone density or weak bones) and fracture (broken bones). Osteoporosis is a major public health problem. One in two women and one in five men over age 50 will have a fracture. Fractures cause pain, disability and reduce life-expectancy. Women with below-average bone density around the time of the menopause might have previously taken hormone replacement (HRT) to prevent osteoporosis, but HRT is much less used now due to side effects. Therefore there is a need for safe, effective and inexpensive preventative interventions for women at risk of osteoporosis. Selenium is a chemical nutrient present in several human proteins, including anti-oxidants. Anti-oxidants may protect against ageing of tissues, including bone, by mopping up damaging reactive oxygen molecules (sometimes called 'free radicals'). Selenium is present in soil, and so is obtained from many foods. However, soil selenium levels are low in Europe, and dietary intake in the UK is below recommended levels. We previously found that women with higher blood selenium levels have stronger bones, but this doesn't prove that giving selenium will improve bone strength. The investigators propose a randomised controlled trial to compare selenium supplements with a placebo (dummy treatment) in women with below-average bone density. The investigators will give selenium (at two different doses) or placebo to 120 women for six months and use blood and urine tests and bone density scans to see if giving selenium does have any effect on bone. The investigators will also do muscle function tests and measurements of free radical molecules.

Detailed Description
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This is a double-blind, randomised, placebo controlled trial. We will evaluate two doses of selenium (50 and 200mcg) vs placebo over six months. Participants are postmenopausal women with osteopenia or osteoporosis (T-score -1.0 to -3.0). The investigators will include participants with any baseline serum selenium concentration for generalisability, but the primary endpoint efficacy analysis will only include women with baseline serum selenium below 120 mcg/l. Primary endpoint: Urinary N-telopeptide of type I collagen (NTX/Cr). Secondary endpoints: other bone turnover markers, BMD, muscle function, thyroid function, blood glucose, anti-oxidant activity, inflammatory markers The investigators will make the primary analysis based on women with baseline serum selenium below 120 mcg/l. To ensure adequate power for this analysis we will plan to recruit 120 women (we expect that 100 of the 120 will have serum selenium below 120 mcg/l based on our previous cross-sectional study). The investigators will review the baseline serum selenium results when 40 women have been recruited to confirm the expected distribution of baseline levels, and we will adjust the total recruitment number accordingly to ensure at least 99 women with serum selenium below 120mcg/l have been randomised for the final primary endpoint intention-to-treat analysis. Participants will be randomised according to a schedule produced by Sheffield Teaching Hospitals pharmacy according to their standard operating procedure. Randomisation will be carried out independently of the study investigators using block randomisation. The blind will only be broken if judged by the PI as clinically necessary for the wellbeing of a participant. The study may be stopped early if the investigators, sponsor or DMEC identify a safety concern. Trial management will be done by the Academic Unit of Bone Metabolism CTIMP group (who meet monthly), and progress reported to the AUBM management group and Lay Panel. We will establish a TSC and DMEC.

Official Title
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The Effect of Selenium Supplementation on Musculoskeletal Health in Older Women Double-blind, Randomised, Placebo-controlled Trial

Conditions
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Osteoporosis

Intervention / Treatment
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* Dietary Supplement: selenase (selenium)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: women age over 55y at least 5y postemenopausal willing and able to give informed consent lumbar spine or total hip BMD T-score between -1.0 and -3.0 not clinically requiring treatment for osteoporosis Exclusion Criteria: diabetes mellitus, thyroid dysfunction, any conditions known to affect bone metabolism (such as inflammatory disease, parathyroid disease, malabsorption ), medications known to affect bone metabolism (such as osteoporosis treatment, aromatase inhibitors, anti-epileptics), alcohol intake >21 units per week, prolonged immobility (>3 months), fracture in the last year, taken selenium supplements in the last year

Ages Eligible for Study
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Minimum Age: 55 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: selenase 200mcg<br>selenium as selenase 200mcg once daily, oral | Dietary Supplement: selenase (selenium)<br>* Selenase (Biosyn, Germany) Sodium selenite pentahydrate<br>|
| Experimental: selenase 50mcg<br>selenium as selenase 50mcg once daily, oral | Dietary Supplement: selenase (selenium)<br>* Selenase (Biosyn, Germany) Sodium selenite pentahydrate<br>|
| Placebo Comparator: placebo<br>matched placebo, once daily, oral | Dietary Supplement: selenase (selenium)<br>* Selenase (Biosyn, Germany) Sodium selenite pentahydrate<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| urine NTX (N-terminal cross-linking telopeptide of type I collagen) | bone resorption marker | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| serum selenium and selenoprotein P | measures of selnium status | 6 months | 
| other biochemical markers of bone turnover | CTX (C-terminal cross-linking telopeptide of type I collagen), osteocalcin, PINP (Procollagen type I N propeptide) | 6 months | 
| bone mineral density | DXA lumbar spine and total hip | 6m | 
| physical function | short physical performance battery and hand grip strength | 6m | 
| anti-oxidant activity | glutathione peroxidase, hydroperoxide, reactive oxygen species | 6m | 
| inflammatory markers | serum interleukin-6, highly senetive c-reative protein | 6m | 
| serum insulin and glucose ratio | safety monitoring for diabetes | 3m, 6m | 
| thyroid stimulating hormone | safety monitoring for thyroid dysfunction | 3m, 6m |