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

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

Study Overview

• Status: Completed
• Conditions: Sarcopenia; Osteoporosis
• Intervention / Treatment: Drug: Non-steroidal anti-inflammatory drug (Ibuprofen); Behavioral: Resistance exercise; Other: placebo; Behavioral: Flexibility training

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 90
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Canada
  • Saskatchewan
    • Saskatoon, Saskatchewan, Canada, S7N5B2
      • College of Kinesiology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 61 years and older (Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Non-steroidal anti-inflammatory drug; ibuprofen after exercise training sessions (400 mg, 3 times per week for 9 months)	Drug: Non-steroidal anti-inflammatory drug (Ibuprofen); 400mg of ibuprofen administered after exercise training session 3 days per week; Other Names: Ibuprofen; Behavioral: Resistance exercise; 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
Placebo Comparator: placebo; placebo after exercise training sessions(3 times per week for 9 months)	Behavioral: Resistance exercise; 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; Other: placebo; placebo designed to mimic experimental drug (ibuprofen)
Experimental: resistance exercise; 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); 400mg of ibuprofen administered after exercise training session 3 days per week; Other Names: Ibuprofen; Other: placebo; placebo designed to mimic experimental drug (ibuprofen)
Sham Comparator: flexibility training; flexibility training to be performed 3 days/week for 1 hour for 9 months	Other: placebo; placebo designed to mimic experimental drug (ibuprofen); Behavioral: Flexibility training; 3 days of full body stretching program (approximately 1 hour) to be performed at participants home unsupervised

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
number of participants with adverse events as a measure of safety and number of participants wit adverse events as a measure of safety and tolerability	adverse events as reported by participants and charted on 'adverse events' form	continuously throughout 9 months

Collaborators and Investigators

• Sponsor: University of Saskatchewan
• Collaborators: Canadian Institutes of Health Research (CIHR)
• Investigators: Principal Investigator: Philip D Chilibeck, PhD, University of Saskatchewan

Publications and helpful links

General Publications

• Krentz JR, Quest B, Farthing JP, Quest DW, Chilibeck PD. The effects of ibuprofen on muscle hypertrophy, strength, and soreness during resistance training. Appl Physiol Nutr Metab. 2008 Jun;33(3):470-5. doi: 10.1139/H08-019.

Study record dates

Study Major Dates

• Study Start: April 1, 2013
• Primary Completion (Actual): July 1, 2014
• Study Completion (Actual): July 1, 2014

Study Registration Dates

• First Submitted: June 20, 2013
• First Submitted That Met QC Criteria: June 24, 2013
• First Posted (Estimate): June 25, 2013

Study Record Updates

• Last Update Posted (Actual): May 5, 2017
• Last Update Submitted That Met QC Criteria: May 2, 2017
• Last Verified: May 1, 2017

More Information

Terms related to this study

• Keywords: exercise; elderly; ibuprofen; women; pQCT
• Additional Relevant MeSH Terms: Metabolic Diseases; Nervous System Diseases; Neurologic Manifestations; Musculoskeletal Diseases; Neuromuscular Manifestations; Pathological Conditions, Anatomical; Bone Diseases; Muscular Atrophy; Atrophy; Bone Diseases, Metabolic; Sarcopenia; Osteoporosis; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Analgesics, Non-Narcotic; Antirheumatic Agents; Cyclooxygenase Inhibitors; Anti-Inflammatory Agents; Ibuprofen; Anti-Inflammatory Agents, Non-Steroidal
• Other Study ID Numbers: 12-256; DC0190GP (Other Grant/Funding Number: CIHR)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No