Ibuprofen Supplementation After Resistance Training and Its Effects on Bone in Older Women

Study Overview
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Brief Summary
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Inflammation increases with aging and is implicated in the reduction of bone mass, muscle mass, and strength. Resistance training is safe and effective for increasing muscle mass and strength in older adults,however resistance training by itself cannot suppress inflammation. Ibuprofen is a non-steroidal anti-inflammatory drug that may provide benefits to muscle mass and strength when given after resistance training sessions in older adults; however, more evidence is required to confirm effects across the lifespan. The objectives are to determine the effect of 9 months of exercise training and ibuprofen supplementation, compared to placebo, in older women (≥65years)on the following dependent variables: bone density, geometry, and architecture muscle mass and strength balance

Detailed Description
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The aim of our study is to create new evidence about the effectiveness and safety of non-steroid anti-inflammatory supplementation (i.e. ibuprofen) combined with exercise to influence positively bone and muscle health in women aged 65 years and older. With aging, there is a significant decrease in bone mineral, muscle mass, and strength, which increases the risk of falls, injuries and fracture especially for women. Direct and indirect health costs associated with osteoporosis and sarcopenia (defined as muscle wasting) are in the billions of dollars and escalating as the proportion of older adults in Canada grows. Low-grade inflammation is a main contributing factor to bone and muscle deterioration with aging but is mitigated by anti-inflammatory drug use. Recent evidence shows resistance exercise training combined with a non-steroidal anti-inflammatory drug (ibuprofen) is effective for increasing bone mineral density in young women. No study has addressed directly the effects of ibuprofen use following resistance exercise on bone and muscle in older women, the population at greatest risk of developing osteoporosis. The primary purpose of this study is to investigate the safety and multiple effects of ibuprofen ingestion following supervised resistance exercise training on bone and muscle in older women (≥65y). PRIMARY HYPOTHESES: Ibuprofen combined with resistance training will maintain hip and lumbar spine areal bone mineral density in older women. Secondary hypotheses are that bone structural properties in the hip and wrist, and muscle mass and strength will be improved by supplementing ibuprofen after resistance training sessions. RESEARCH PLAN: The study will use a repeated measures, parallel group randomized design where 100 women (≥65 y) will be randomized to one of 4 groups: 1) Exercise and ibuprofen (400 mg immediately after exercise); 2) Exercise and ibuprofen placebo; 3) Placebo exercise and ibuprofen, 4) Placebo exercise and ibuprofen placebo. Women will participate in the exercise sessions 3 days per week. The intervention will be 9 months in duration. Dual energy X-ray absorptiometry (DXA) will be used to assess hip and lumbar spine areal bone mineral density, as well as geometric changes in hip structure, and whole body lean tissue (i.e. muscle) mass. Peripheral quantitative computed tomography (pQCT) and high-resolution-pQCT will allow us to investigate detailed changes in bone microarchitecture at the wrist and muscle cross-sectional area in the forearm in response to the intervention. Safety will be addressed by closely monitoring adverse events. RELEVANCE: This pilot study potentially drives a novel post-market use of ibuprofen. In addition, it permits our developing research team a foray into preliminary data collection to inform a larger randomized controlled trial (RCT) application to CIHR.

Official Title
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Ibuprofen Supplementation After Resistance Training and Its Effects on Bone in Older Women

Conditions
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Sarcopenia, Osteoporosis

Intervention / Treatment
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* Drug: Non-steroidal anti-inflammatory drug (Ibuprofen)
* Other: placebo
* Behavioral: Resistance exercise
* Behavioral: Flexibility training


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: women >65yrs Exclusion Criteria: high risk of fracture use of bisphosphonates, hormone replacement therapy, selective estrogen receptor modulators, PTH, or calcitonin within the past 12 months taking medications that affect bone mineral metabolism have diseases that are known to affect bone mineral metabolism have severe osteoarthritis currently a smoker currently participating in moderate-vigorous resistance-exercise training more than once per week

Ages Eligible for Study
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Minimum Age: 65 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: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Non-steroidal anti-inflammatory drug<br>ibuprofen after exercise training sessions (400 mg, 3 times per week for 9 months) | Drug: Non-steroidal anti-inflammatory drug (Ibuprofen)<br>* 400mg of ibuprofen administered after exercise training session 3 days per week<br>* Other names: Ibuprofen;Behavioral: Resistance exercise<br>* 3 sets of 8-12 repetitions of resistance exercise (full body with a focus on the distal radius) completed 3 days/week under supervision in the research gym<br>|
| Placebo Comparator: placebo<br>placebo after exercise training sessions(3 times per week for 9 months) | Other: placebo<br>* placebo designed to mimic experimental drug (ibuprofen)<br>Behavioral: Resistance exercise<br>* 3 sets of 8-12 repetitions of resistance exercise (full body with a focus on the distal radius) completed 3 days/week under supervision in the research gym<br>|
| Experimental: resistance exercise<br>3 sets of 8-12 repetitions of resistance exercises focused on distal radius to be performed 3 times/week for 9 months | Drug: Non-steroidal anti-inflammatory drug (Ibuprofen)<br>* 400mg of ibuprofen administered after exercise training session 3 days per week<br>* Other names: Ibuprofen;Other: placebo<br>* placebo designed to mimic experimental drug (ibuprofen)<br>|
| Sham Comparator: flexibility training<br>flexibility training to be performed 3 days/week for 1 hour for 9 months | Other: placebo<br>* placebo designed to mimic experimental drug (ibuprofen)<br>Behavioral: Flexibility training<br>* 3 days of full body stretching program (approximately 1 hour) to be performed at participants home unsupervised<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| change from baseline in aBMD of the proximal femur and lumbar spine at 9 months | areal bone mineral density of the proximal femure and lumbar spine assessed by dual energy x-ray absorptiometry | baseline and 9 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| change from baseline in femoral neck section modulus at 9 months | femoral neck section modulus assessed by dual energy x-ray absorptiometry | baseline and 9 months | 
| change from baseline in distal radius Bone Strength Index at 9 months | distal radius Bone Strength Index assessed by high resolution peripheral quantitative computed tomography | baseline and 9 months | 
| change from baseline in radial shaft Stress Strain Index at 9 months | radial shaft Stress Strain Index assessed by peripheral quantitative computed tomography | baseline and 9 months | 
| change from baseline in radial shaft muscle cross-sectional area at 9 months | radial shaft muscle cross-sectional area assessed by peripheral quantitative computed tomography | baseline and 9 months | 
| change from baseline in total body lean tissue mass at 9 months | total body lean tissue mass assessed by dual energy x-ray absorptiometry | baseline and 9 months | 
| change from baseline in muscular strength at 9 months | muscular strength assessed by 1 repetition maximum bicep curl and leg press | baseline and 9 months | 
| change from baseline in balance performance at 9 months | balance performance assessed by tandem walk on balance board | baseline and 9 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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pQCT, elderly, women, exercise, ibuprofen