MOXI: Myogenic and Osteogenic Responses to eXercise and Ibuprofen

• Sponsor: University of Colorado, Denver (Other)
• Overall Status: Completed
• CT.gov ID: NCT00462722
• Collaborator: National Institute on Aging (NIA) (NIH)
• Enrollment: 159
• Location: 1
• Arms: 3
• Duration (Months): 53
• Patients Per Site Per Month: 3

Study Details

Study Description

Brief Summary

The purpose of this study is to determine if the use of ibuprofen blocks the benefits of exercise to build bone and muscle mass.

Condition or Disease	Intervention/Treatment	Phase
Aging; Physical Fitness	Drug: Ibuprofen; Drug: Placebo; Behavioral: musculoskeletal-loading exercise	N/A

Detailed Description

People are advised to engage in weight-bearing physical activity to help prevent the loss of bone and muscle mass that occurs with aging. There is evidence from studies of animals that non-steroidal anti-inflammatory drugs (NSAIDS), such as ibuprofen, block some of the bone- and muscle-building effects of exercise. The aim of this study is to determine whether use of ibuprofen, either before or after exercise, blocks the benefits of exercise training on bone and skeletal muscle in older women and men. The hypothesis is that taking ibuprofen before exercise will block some of the effects of exercise training to increase bone density and muscle mass.

Women and men aged 60-75 years will complete a supervised, 9-month exercise training program designed to increase bone and muscle mass. The training will include weight lifting and weight-bearing exercises, such as jumping in place and treadmill walking, up to 5 days per week. Participants will be randomly assigned to take 1 of 3 study pill combinations before and after each exercise session. The combinations of study pills will be: placebo before/placebo after, placebo before/ibuprofen after, or ibuprofen before/placebo after. The dose of ibuprofen will be 400 mg. Bone density of the hip and spine, body composition (total body muscle and fat), and markers of bone turnover in the blood will be measured before and after 4.5 and 9 months of training. Muscle cross-sectional area of the thigh will be measured by CT before and after 9 months of training. A subset of participants will have biopsies of the thigh muscle before and after training to measure proteins and genes associated with muscle build-up and breakdown.

Volunteers who do not use ibuprofen, aspirin, or acetaminophen more than 3 days per month will be enrolled. People with intolerance to ibuprofen or related drugs, cardiovascular disease, or orthopedic problems that limit exercise will be excluded from the study.

Study Design

• Study Type: Interventional
• Actual Enrollment: 159 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Official Title: COX Inhibition & Musculoskeletal Responses to Exercise
• Study Start Date: Jul 1, 2007
• Actual Primary Completion Date: Dec 1, 2011
• Actual Study Completion Date: Dec 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: Placebo pre and post exercise placebo before and after musculoskeletal-loading exercise	Drug: Placebo; with each exercise session (up to 5 days per week) for 9 months; Behavioral: musculoskeletal-loading exercise; Exercise training program designed to increase bone and muscle mass, including weight lifting and weight-bearing exercises such as jumping in place and treadmill walking up to 5 days per week for 9 months
Experimental: Placebo pre and ibuprofen post exercise placebo before and ibuprofen after musculoskeletal-loading exercise	Drug: Ibuprofen; 400 mg with each exercise session (up to 5 days per week) for 9 months; Other Names: Motrin Advil ; Drug: Placebo; with each exercise session (up to 5 days per week) for 9 months; Behavioral: musculoskeletal-loading exercise; Exercise training program designed to increase bone and muscle mass, including weight lifting and weight-bearing exercises such as jumping in place and treadmill walking up to 5 days per week for 9 months
Experimental: Ibuprofen pre and placebo post exercise ibuprofen before and placebo after musculoskeletal-loading exercise	Drug: Ibuprofen; 400 mg with each exercise session (up to 5 days per week) for 9 months; Other Names: Motrin Advil ; Drug: Placebo; with each exercise session (up to 5 days per week) for 9 months; Behavioral: musculoskeletal-loading exercise; Exercise training program designed to increase bone and muscle mass, including weight lifting and weight-bearing exercises such as jumping in place and treadmill walking up to 5 days per week for 9 months

Outcome Measures

Primary Outcome Measures

1. Percentage Change From Baseline in Lumbar Spine Bone Mineral Density (BMD) at 9 Months [Baseline and after 9 months of training]

2. Percentage Change From Baseline in Total Hip Bone Mineral Density (BMD) at 9 Months [Baseline and after 9 months of training]

3. Change From Baseline in Fat-free Mass at 9 Months [Baseline and after 9 months of training]

Secondary Outcome Measures

1. Percentage Change From Baseline in Femoral Neck Bone Mineral Density (BMD) at 9 Months [Baseline and after 9 months of training]

2. Percentage Change From Baseline in Trochanter Bone Mineral Density (BMD) at 9 Months [Baseline and after 9 months of training]

3. Percentage Change From Baseline in Sub-trochanter Bone Mineral Density (BMD) at 9 Months [Baseline and after 9 months of training]

4. Change in Thigh Cross-sectional Muscle Area [Baseline and after 9 months of training]

5. Bone Turnover Markers [Baseline, and after 4.5 & 9 months of training]

6. Expression of Selected Proteins and Genes Associated With Muscle Build-up and Breakdown [Baseline and after 9 months of training]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 60 Years to 75 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• Aged 60 to 75 years

• Willing to participate in a 9-month supervised exercise program that will start at a moderate intensity and gradually progress to a vigorous intensity

• Not currently performing regular, moderate-to-vigorous weight-bearing or weight-lifting exercise

• Average use of NSAIDs (including low-dose aspirin) or acetaminophen less than 3 days per month

Exclusion Criteria:

• Relative or absolute contraindications to regular use of NSAIDs

• Known allergy or intolerance (heartburn, stomach pain, nausea, vomiting) to NSAIDs; controlled GERD(Gastroesophageal Reflux Disease), if not related to NSAID use, will not be an exclusion criterion

• Proton Pump Inhibitor (PPI) use if dose is unstable or if using for less than 6 months prior to study enrollment

• History of peptic ulcer or upper GI bleeding

• Anemia

• Asthma with bronchospasm induced by aspirin or other NSAIDs

• Moderate or severe renal impairment defined as a calculated creatinine clearance

• Chronic hepatobiliary disease, conservatively defined as liver function tests greater than 1.5 times the upper limit of normal (if such values are obtained on initial screening and thought to be transient in nature, repeated testing will be allowed)

• Hyperkalemia

• Osteoporosis

• Diabetes mellitus requiring pharmacologic therapy

• Congestive heart failure

• Uncontrolled hypertension; use of thiazide diuretics will be allowed if on a stable dose for at least 6 months

• Cardiovascular disease

• Thyroid dysfunction

• Orthopedic problems (e.g., chronic back pain, severe osteoarthritis, rheumatoid arthritis) that limit the ability to perform vigorous exercise and increase the likelihood that the volunteer will use pain medications other than the study pills

• Certain use of medications, including

• Drugs that are known to alter bone metabolism (e.g., estrogen, SERMs(Selective estrogen-receptor modulators), testosterone, bisphosphonates, teriparatide, calcitonin, GnRH(Gonadotropin-releasing hormone) agonists)

• Chronic use of oral corticosteroids or any use in the previous 6 months (use of inhaled steroids will not be an exclusion criterion based on a meta-analysis documenting that the effect on bone is not significant)

• Average use of acetaminophen or NSAIDs, including low-dose aspirin, greater than 3 days per month; volunteers using aspirin for primary prevention may enroll in the study if they discontinue aspirin therapy for the 9-month intervention period

• Anticoagulants (e.g., warfarin, clopidogrel)

• Narcotics

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Colorado Denver	Aurora	Colorado	United States	80045

Sponsors and Collaborators

• University of Colorado, Denver
• National Institute on Aging (NIA)

Investigators

• Principal Investigator: Wendy Kohrt, PhD, University of Colorado, Denver

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Data analysis plan MOXI Study

Publications

• Chow JW, Chambers TJ. Indomethacin has distinct early and late actions on bone formation induced by mechanical stimulation. Am J Physiol. 1994 Aug;267(2 Pt 1):E287-92.
• Li J, Burr DB, Turner CH. Suppression of prostaglandin synthesis with NS-398 has different effects on endocortical and periosteal bone formation induced by mechanical loading. Calcif Tissue Int. 2002 Apr;70(4):320-9. Epub 2002 Mar 26.
• Trappe TA, White F, Lambert CP, Cesar D, Hellerstein M, Evans WJ. Effect of ibuprofen and acetaminophen on postexercise muscle protein synthesis. Am J Physiol Endocrinol Metab. 2002 Mar;282(3):E551-6.

• Responsible Party: University of Colorado, Denver
• ClinicalTrials.gov Identifier: NCT00462722
• Other Study ID Numbers: 06-0769; R01AG018857
• First Posted: Apr 19, 2007
• Last Update Posted: Nov 1, 2015
• Last Verified: Oct 1, 2015

• Keywords provided by University of Colorado, Denver: body composition; bone density; cyclooxygenase inhibitor; bone metabolism; muscle function; muscle strength
• Additional relevant MeSH terms: Ibuprofen

Study Results

Participant Flow

Arm/Group Title	Placebo Pre and Post Exercise	Ibuprofen Pre and Placebo Post Exercise	Placebo Pre and Ibuprofen Post Exercise
Arm/Group Description	placebo before and after musculoskeletal-loading exercise Placebo: with each exercise session (up to 5 days per week) for 9 months musculoskeletal-loading exercise: Exercise training program designed to increase bone and muscle mass, including weight lifting and weight-bearing exercises such as jumping in place and treadmill walking up to 5 days per week for 9 months	ibuprofen before and placebo after musculoskeletal-loading exercise Ibuprofen: 400 mg with each exercise session (up to 5 days per week) for 9 months Placebo: with each exercise session (up to 5 days per week) for 9 months musculoskeletal-loading exercise: Exercise training program designed to increase bone and muscle mass, including weight lifting and weight-bearing exercises such as jumping in place and treadmill walking up to 5 days per week for 9 months	placebo before and ibuprofen after musculoskeletal-loading exercise Ibuprofen: 400 mg with each exercise session (up to 5 days per week) for 9 months Placebo: with each exercise session (up to 5 days per week) for 9 months musculoskeletal-loading exercise: Exercise training program designed to increase bone and muscle mass, including weight lifting and weight-bearing exercises such as jumping in place and treadmill walking up to 5 days per week for 9 months
Period Title: Overall Study
STARTED	50	55	54
COMPLETED	37	51	42
NOT COMPLETED	13	4	12

Baseline Characteristics

Arm/Group Title	Placebo Pre and Post Exercise	Ibuprofen Pre and Placebo Post Exercise	Placebo Pre and Ibuprofen Post Exercise	Total
Arm/Group Description	placebo before and after musculoskeletal-loading exercise Placebo: with each exercise session (up to 5 days per week) for 9 months musculoskeletal-loading exercise: Exercise training program designed to increase bone and muscle mass, including weight lifting and weight-bearing exercises such as jumping in place and treadmill walking up to 5 days per week for 9 months	ibuprofen before and placebo after musculoskeletal-loading exercise Ibuprofen: 400 mg with each exercise session (up to 5 days per week) for 9 months Placebo: with each exercise session (up to 5 days per week) for 9 months musculoskeletal-loading exercise: Exercise training program designed to increase bone and muscle mass, including weight lifting and weight-bearing exercises such as jumping in place and treadmill walking up to 5 days per week for 9 months	placebo before and ibuprofen after musculoskeletal-loading exercise Ibuprofen: 400 mg with each exercise session (up to 5 days per week) for 9 months Placebo: with each exercise session (up to 5 days per week) for 9 months musculoskeletal-loading exercise: Exercise training program designed to increase bone and muscle mass, including weight lifting and weight-bearing exercises such as jumping in place and treadmill walking up to 5 days per week for 9 months	Total of all reporting groups
Overall Participants	37	51	42	130
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	64 (4)	64 (4)	66 (4)	64 (4)
Sex: Female, Male (Count of Participants)
Female	23 62.2%	32 62.7%	27 64.3%	82 63.1%
Male	14 37.8%	19 37.3%	15 35.7%	48 36.9%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	2 5.4%	2 3.9%	1 2.4%	5 3.8%
Not Hispanic or Latino	35 94.6%	49 96.1%	41 97.6%	125 96.2%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	1 2%	1 2.4%	2 1.5%
Asian	1 2.7%	1 2%	1 2.4%	3 2.3%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%
Black or African American	0 0%	2 3.9%	5 11.9%	7 5.4%
White	33 89.2%	47 92.2%	35 83.3%	115 88.5%
More than one race	3 8.1%	0 0%	0 0%	3 2.3%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
United States	37 100%	51 100%	42 100%	130 100%

Outcome Measures

1. Primary Outcome

Title	Percentage Change From Baseline in Lumbar Spine Bone Mineral Density (BMD) at 9 Months
Time Frame	Baseline and after 9 months of training

Outcome Measure Data

Analysis Population Description

One participant in the "Ibuprofen pre and placebo post exercise" group had an uninterpretable spine scan.

Arm/Group Title	Placebo Pre and Post Exercise	Ibuprofen Pre and Placebo Post Exercise	Placebo Pre and Ibuprofen Post Exercise
Arm/Group Description	placebo before and after musculoskeletal-loading exercise Placebo: with each exercise session (up to 5 days per week) for 9 months musculoskeletal-loading exercise: Exercise training program designed to increase bone and muscle mass, including weight lifting and weight-bearing exercises such as jumping in place and treadmill walking up to 5 days per week for 9 months	ibuprofen before and placebo after musculoskeletal-loading exercise Ibuprofen: 400 mg with each exercise session (up to 5 days per week) for 9 months Placebo: with each exercise session (up to 5 days per week) for 9 months musculoskeletal-loading exercise: Exercise training program designed to increase bone and muscle mass, including weight lifting and weight-bearing exercises such as jumping in place and treadmill walking up to 5 days per week for 9 months	placebo before and ibuprofen after musculoskeletal-loading exercise Ibuprofen: 400 mg with each exercise session (up to 5 days per week) for 9 months Placebo: with each exercise session (up to 5 days per week) for 9 months musculoskeletal-loading exercise: Exercise training program designed to increase bone and muscle mass, including weight lifting and weight-bearing exercises such as jumping in place and treadmill walking up to 5 days per week for 9 months
Measure Participants	37	50	42
Mean (Standard Deviation) [Percentage change in lumbar spine BMD]	1.3 (2.8)	1.5 (2.5)	0.9 (2.2)

2. Primary Outcome

Title	Percentage Change From Baseline in Total Hip Bone Mineral Density (BMD) at 9 Months
Time Frame	Baseline and after 9 months of training

Outcome Measure Data

Analysis Population Description

One participant in the "Placebo pre and post exercise" group and two participants in the "Ibuprofen pre and placebo post exercise" group had uninterpretable hip scans.

Arm/Group Title	Placebo Pre and Post Exercise	Ibuprofen Pre and Placebo Post Exercise	Placebo Pre and Ibuprofen Post Exercise
Arm/Group Description	placebo before and after musculoskeletal-loading exercise Placebo: with each exercise session (up to 5 days per week) for 9 months musculoskeletal-loading exercise: Exercise training program designed to increase bone and muscle mass, including weight lifting and weight-bearing exercises such as jumping in place and treadmill walking up to 5 days per week for 9 months	ibuprofen before and placebo after musculoskeletal-loading exercise Ibuprofen: 400 mg with each exercise session (up to 5 days per week) for 9 months Placebo: with each exercise session (up to 5 days per week) for 9 months musculoskeletal-loading exercise: Exercise training program designed to increase bone and muscle mass, including weight lifting and weight-bearing exercises such as jumping in place and treadmill walking up to 5 days per week for 9 months	placebo before and ibuprofen after musculoskeletal-loading exercise Ibuprofen: 400 mg with each exercise session (up to 5 days per week) for 9 months Placebo: with each exercise session (up to 5 days per week) for 9 months musculoskeletal-loading exercise: Exercise training program designed to increase bone and muscle mass, including weight lifting and weight-bearing exercises such as jumping in place and treadmill walking up to 5 days per week for 9 months
Measure Participants	36	49	42
Mean (Standard Deviation) [percentage change in total hip BMD]	0.5 (2.6)	0.0 (1.9)	-0.3 (2.0)

3. Primary Outcome

Title	Change From Baseline in Fat-free Mass at 9 Months
Time Frame	Baseline and after 9 months of training

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo Pre and Post Exercise	Ibuprofen Pre and Placebo Post Exercise	Placebo Pre and Ibuprofen Post Exercise
Arm/Group Description	placebo before and after musculoskeletal-loading exercise Placebo: with each exercise session (up to 5 days per week) for 9 months musculoskeletal-loading exercise: Exercise training program designed to increase bone and muscle mass, including weight lifting and weight-bearing exercises such as jumping in place and treadmill walking up to 5 days per week for 9 months	ibuprofen before and placebo after musculoskeletal-loading exercise Ibuprofen: 400 mg with each exercise session (up to 5 days per week) for 9 months Placebo: with each exercise session (up to 5 days per week) for 9 months musculoskeletal-loading exercise: Exercise training program designed to increase bone and muscle mass, including weight lifting and weight-bearing exercises such as jumping in place and treadmill walking up to 5 days per week for 9 months	placebo before and ibuprofen after musculoskeletal-loading exercise Ibuprofen: 400 mg with each exercise session (up to 5 days per week) for 9 months Placebo: with each exercise session (up to 5 days per week) for 9 months musculoskeletal-loading exercise: Exercise training program designed to increase bone and muscle mass, including weight lifting and weight-bearing exercises such as jumping in place and treadmill walking up to 5 days per week for 9 months
Measure Participants	37	51	42
Mean (Standard Deviation) [change in kg]	0.6 (1.1)	0.4 (1.6)	0.6 (1.4)

4. Secondary Outcome

Title	Percentage Change From Baseline in Femoral Neck Bone Mineral Density (BMD) at 9 Months
Time Frame	Baseline and after 9 months of training

Outcome Measure Data

Analysis Population Description

One participant in the "Placebo pre and post exercise" group and two participants in the "Ibuprofen pre and placebo post exercise" group had uninterpretable spine scans.

Arm/Group Title	Placebo Pre and Post Exercise	Ibuprofen Pre and Placebo Post Exercise	Placebo Pre and Ibuprofen Post Exercise
Arm/Group Description	placebo before and after musculoskeletal-loading exercise Placebo: with each exercise session (up to 5 days per week) for 9 months musculoskeletal-loading exercise: Exercise training program designed to increase bone and muscle mass, including weight lifting and weight-bearing exercises such as jumping in place and treadmill walking up to 5 days per week for 9 months	ibuprofen before and placebo after musculoskeletal-loading exercise Ibuprofen: 400 mg with each exercise session (up to 5 days per week) for 9 months Placebo: with each exercise session (up to 5 days per week) for 9 months musculoskeletal-loading exercise: Exercise training program designed to increase bone and muscle mass, including weight lifting and weight-bearing exercises such as jumping in place and treadmill walking up to 5 days per week for 9 months	placebo before and ibuprofen after musculoskeletal-loading exercise Ibuprofen: 400 mg with each exercise session (up to 5 days per week) for 9 months Placebo: with each exercise session (up to 5 days per week) for 9 months musculoskeletal-loading exercise: Exercise training program designed to increase bone and muscle mass, including weight lifting and weight-bearing exercises such as jumping in place and treadmill walking up to 5 days per week for 9 months
Measure Participants	36	49	42
Mean (Standard Deviation) [percentage change in BMD]	0.2 (2.9)	0.2 (2.8)	-0.1 (2.1)

5. Secondary Outcome

Title	Percentage Change From Baseline in Trochanter Bone Mineral Density (BMD) at 9 Months
Time Frame	Baseline and after 9 months of training

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo Pre and Post Exercise	Ibuprofen Pre and Placebo Post Exercise	Placebo Pre and Ibuprofen Post Exercise
Arm/Group Description	placebo before and after musculoskeletal-loading exercise Placebo: with each exercise session (up to 5 days per week) for 9 months musculoskeletal-loading exercise: Exercise training program designed to increase bone and muscle mass, including weight lifting and weight-bearing exercises such as jumping in place and treadmill walking up to 5 days per week for 9 months	ibuprofen before and placebo after musculoskeletal-loading exercise Ibuprofen: 400 mg with each exercise session (up to 5 days per week) for 9 months Placebo: with each exercise session (up to 5 days per week) for 9 months musculoskeletal-loading exercise: Exercise training program designed to increase bone and muscle mass, including weight lifting and weight-bearing exercises such as jumping in place and treadmill walking up to 5 days per week for 9 months	placebo before and ibuprofen after musculoskeletal-loading exercise Ibuprofen: 400 mg with each exercise session (up to 5 days per week) for 9 months Placebo: with each exercise session (up to 5 days per week) for 9 months musculoskeletal-loading exercise: Exercise training program designed to increase bone and muscle mass, including weight lifting and weight-bearing exercises such as jumping in place and treadmill walking up to 5 days per week for 9 months
Measure Participants	36	49	42
Mean (Standard Deviation) [percentage change in BMD]	1.1 (3.1)	0.0 (2.3)	-0.1 (2.7)

6. Secondary Outcome

Title	Percentage Change From Baseline in Sub-trochanter Bone Mineral Density (BMD) at 9 Months
Time Frame	Baseline and after 9 months of training

Outcome Measure Data

Analysis Population Description

One participant in the "Placebo pre and post exercise" group and two participants in the "Ibuprofen pre and placebo post exercise" groups had uninterpretable hip scans.

Arm/Group Title	Placebo Pre and Post Exercise	Ibuprofen Pre and Placebo Post Exercise	Placebo Pre and Ibuprofen Post Exercise
Arm/Group Description	placebo before and after musculoskeletal-loading exercise Placebo: with each exercise session (up to 5 days per week) for 9 months musculoskeletal-loading exercise: Exercise training program designed to increase bone and muscle mass, including weight lifting and weight-bearing exercises such as jumping in place and treadmill walking up to 5 days per week for 9 months	ibuprofen before and placebo after musculoskeletal-loading exercise Ibuprofen: 400 mg with each exercise session (up to 5 days per week) for 9 months Placebo: with each exercise session (up to 5 days per week) for 9 months musculoskeletal-loading exercise: Exercise training program designed to increase bone and muscle mass, including weight lifting and weight-bearing exercises such as jumping in place and treadmill walking up to 5 days per week for 9 months	placebo before and ibuprofen after musculoskeletal-loading exercise Ibuprofen: 400 mg with each exercise session (up to 5 days per week) for 9 months Placebo: with each exercise session (up to 5 days per week) for 9 months musculoskeletal-loading exercise: Exercise training program designed to increase bone and muscle mass, including weight lifting and weight-bearing exercises such as jumping in place and treadmill walking up to 5 days per week for 9 months
Measure Participants	36	49	42
Mean (Standard Deviation) [percentage change in BMD]	0.5 (3.4)	0.0 (2.3)	-0.3 (2.5)

7. Secondary Outcome

Title	Change in Thigh Cross-sectional Muscle Area
Time Frame	Baseline and after 9 months of training

Outcome Measure Data

Analysis Population Description

Because of the costs associated with data analysis for this secondary outcome, we did not pursue the analysis after learning the results of the primary outcome (fat-free mass).

Arm/Group Title	Placebo Pre and Post Exercise	Ibuprofen Pre and Placebo Post Exercise	Placebo Pre and Ibuprofen Post Exercise
Arm/Group Description	placebo before and after musculoskeletal-loading exercise Placebo: with each exercise session (up to 5 days per week) for 9 months musculoskeletal-loading exercise: Exercise training program designed to increase bone and muscle mass, including weight lifting and weight-bearing exercises such as jumping in place and treadmill walking up to 5 days per week for 9 months	ibuprofen before and placebo after musculoskeletal-loading exercise Ibuprofen: 400 mg with each exercise session (up to 5 days per week) for 9 months Placebo: with each exercise session (up to 5 days per week) for 9 months musculoskeletal-loading exercise: Exercise training program designed to increase bone and muscle mass, including weight lifting and weight-bearing exercises such as jumping in place and treadmill walking up to 5 days per week for 9 months	placebo before and ibuprofen after musculoskeletal-loading exercise Ibuprofen: 400 mg with each exercise session (up to 5 days per week) for 9 months Placebo: with each exercise session (up to 5 days per week) for 9 months musculoskeletal-loading exercise: Exercise training program designed to increase bone and muscle mass, including weight lifting and weight-bearing exercises such as jumping in place and treadmill walking up to 5 days per week for 9 months
Measure Participants	0	0	0

8. Secondary Outcome

Title	Bone Turnover Markers
Time Frame	Baseline, and after 4.5 & 9 months of training

Outcome Measure Data

Analysis Population Description

Because of the costs associated with the assays and data analysis of bone turnover markers, we did not pursue data collection after learning of the primary outcomes (changes in BMD).

Arm/Group Title	Placebo Pre and Post Exercise	Ibuprofen Pre and Placebo Post Exercise	Placebo Pre and Ibuprofen Post Exercise
Arm/Group Description	placebo before and after musculoskeletal-loading exercise Placebo: with each exercise session (up to 5 days per week) for 9 months musculoskeletal-loading exercise: Exercise training program designed to increase bone and muscle mass, including weight lifting and weight-bearing exercises such as jumping in place and treadmill walking up to 5 days per week for 9 months	ibuprofen before and placebo after musculoskeletal-loading exercise Ibuprofen: 400 mg with each exercise session (up to 5 days per week) for 9 months Placebo: with each exercise session (up to 5 days per week) for 9 months musculoskeletal-loading exercise: Exercise training program designed to increase bone and muscle mass, including weight lifting and weight-bearing exercises such as jumping in place and treadmill walking up to 5 days per week for 9 months	placebo before and ibuprofen after musculoskeletal-loading exercise Ibuprofen: 400 mg with each exercise session (up to 5 days per week) for 9 months Placebo: with each exercise session (up to 5 days per week) for 9 months musculoskeletal-loading exercise: Exercise training program designed to increase bone and muscle mass, including weight lifting and weight-bearing exercises such as jumping in place and treadmill walking up to 5 days per week for 9 months
Measure Participants	0	0	0

9. Secondary Outcome

Title	Expression of Selected Proteins and Genes Associated With Muscle Build-up and Breakdown
Time Frame	Baseline and after 9 months of training

Outcome Measure Data

Analysis Population Description

Because of the costs associated with gene and protein expression techniques and data reduction, we did not pursue this secondary outcome after learning the results of the primary outcome (change in fat-free mass).

Arm/Group Title	Placebo Pre and Post Exercise	Ibuprofen Pre and Placebo Post Exercise	Placebo Pre and Ibuprofen Post Exercise
Arm/Group Description	placebo before and after musculoskeletal-loading exercise Placebo: with each exercise session (up to 5 days per week) for 9 months musculoskeletal-loading exercise: Exercise training program designed to increase bone and muscle mass, including weight lifting and weight-bearing exercises such as jumping in place and treadmill walking up to 5 days per week for 9 months	ibuprofen before and placebo after musculoskeletal-loading exercise Ibuprofen: 400 mg with each exercise session (up to 5 days per week) for 9 months Placebo: with each exercise session (up to 5 days per week) for 9 months musculoskeletal-loading exercise: Exercise training program designed to increase bone and muscle mass, including weight lifting and weight-bearing exercises such as jumping in place and treadmill walking up to 5 days per week for 9 months	placebo before and ibuprofen after musculoskeletal-loading exercise Ibuprofen: 400 mg with each exercise session (up to 5 days per week) for 9 months Placebo: with each exercise session (up to 5 days per week) for 9 months musculoskeletal-loading exercise: Exercise training program designed to increase bone and muscle mass, including weight lifting and weight-bearing exercises such as jumping in place and treadmill walking up to 5 days per week for 9 months
Measure Participants	0	0	0

Adverse Events

Arm/Group Title	Placebo Pre and Post Exercise		Ibuprofen Pre and Placebo Post Exercise		Placebo Pre and Ibuprofen Post Exercise
Arm/Group Description	placebo before and after musculoskeletal-loading exercise Placebo: with each exercise session (up to 5 days per week) for 9 months musculoskeletal-loading exercise: Exercise training program designed to increase bone and muscle mass, including weight lifting and weight-bearing exercises such as jumping in place and treadmill walking up to 5 days per week for 9 months		ibuprofen before and placebo after musculoskeletal-loading exercise Ibuprofen: 400 mg with each exercise session (up to 5 days per week) for 9 months Placebo: with each exercise session (up to 5 days per week) for 9 months musculoskeletal-loading exercise: Exercise training program designed to increase bone and muscle mass, including weight lifting and weight-bearing exercises such as jumping in place and treadmill walking up to 5 days per week for 9 months		placebo before and ibuprofen after musculoskeletal-loading exercise Ibuprofen: 400 mg with each exercise session (up to 5 days per week) for 9 months Placebo: with each exercise session (up to 5 days per week) for 9 months musculoskeletal-loading exercise: Exercise training program designed to increase bone and muscle mass, including weight lifting and weight-bearing exercises such as jumping in place and treadmill walking up to 5 days per week for 9 months
All Cause Mortality
	Placebo Pre and Post Exercise		Ibuprofen Pre and Placebo Post Exercise		Placebo Pre and Ibuprofen Post Exercise
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Placebo Pre and Post Exercise		Ibuprofen Pre and Placebo Post Exercise		Placebo Pre and Ibuprofen Post Exercise
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/37 (0%)		0/51 (0%)		0/42 (0%)
Other (Not Including Serious) Adverse Events
	Placebo Pre and Post Exercise		Ibuprofen Pre and Placebo Post Exercise		Placebo Pre and Ibuprofen Post Exercise
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/37 (0%)		1/51 (2%)		0/42 (0%)
Renal and urinary disorders
change in estimated glomerular filtration rate (eGFR)	0/37 (0%)	0	1/51 (2%)	1	0/42 (0%)	0

Limitations/Caveats

The study did not include a no-exercise control group. The variability in the BMD responses was greater than expected. The results may be specific to ibuprofen and not to other NSAIDs.

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Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.