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The purpose of this study is to determine the effects of a single dose of non-steroidal anti-inflammatory drugs on post-exercise markers of bone and muscle metabolism.
This protocol intends to determine how consuming a single dose of a non-steroidal anti-inflammatory drug (NSAID) affects circulating bone metabolism biomarkers and markers of damage skeletal muscle in response to a bout of plyometric exercise. This will be accomplished using a four trial, placebo-controlled crossover design with trials examining ibuprofen, celecoxib, flurbiprofen and placebo. These particular NSAIDs were chosen because of their widespread use in military populations and differing molecular mechanisms, which could cause differing effects on bone and muscle. Two hours after of consuming a single dose of an NSAID, participants will perform 10 sets of 10 plyometric jumps to induce a mechanical loading stimulus the bone and muscle tissues. Blood, urine, and muscle biopsy samples will be collected before and up to four hours after exercise. Biomarkers representing bone and muscle metabolism will determine the magnitude of adaptive responses to plyometric exercise while using NSAIDs.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Ibuprofen | Experimental | Participants will consume a single dose of ibuprofen prior to a plyometric exercise bout |
|
| Celecoxib | Experimental | Participants will consume a single dose of celecoxib prior to a plyometric exercise bout |
|
| Flurbiprofen | Experimental | Participants will consume a single dose of flurbiprofen prior to a plyometric exercise bout |
|
| Placebo | Placebo Comparator | Participants will consume a single dose of an inert placebo prior to a plyometric exercise bout |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Ibuprofen 800 mg | Drug | Ibuprofen taken orally 2 hours prior to exercise |
|
| Measure | Description | Time Frame |
|---|---|---|
| Change from baseline circulating marker of bone formation | Concentration (pg/mL) of serum N-terminal propeptide of type 1 collagen (P1NP) | Change from pre-exercise to 4 hours post-exercise |
| Measure | Description | Time Frame |
|---|---|---|
| Change from baseline circulating marker of bone resorption | Concentration (pg/mL) of serum C-terminal propeptide of type I collagen (CTX) | Change from pre-exercise to 4 hours post-exercise |
| Markers of muscle inflammation |
| Measure | Description | Time Frame |
|---|---|---|
| Muscle protein synthesis | ribosomal protein S6 (p-RPS6) protein concentration in muscle biopsy tissue | Change from pre-exercise to 3 hours post-exercise |
Inclusion Criteria:
Exclusion Criteria:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| United States Army Research Institute of Environmental Medicine | Natick | Massachusetts | 01760 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 33641442 | Background | Staab JS, Kolb AL, Tomlinson RE, Pajevic PD, Matheny RW Jr, Hughes JM. Emerging evidence that adaptive bone formation inhibition by non-steroidal anti-inflammatory drugs increases stress fracture risk. Exp Biol Med (Maywood). 2021 May;246(9):1104-1111. doi: 10.1177/1535370221993098. Epub 2021 Feb 27. | |
| 25642444 | Background |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| ICF | No | No | Yes | Informed Consent Form | Jul 27, 2022 | Aug 16, 2022 | ICF_000.pdf |
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| ID | Term |
|---|---|
| D001862 | Bone Resorption |
| D015775 | Fractures, Stress |
| ID | Term |
|---|---|
| D001847 | Bone Diseases |
| D009140 | Musculoskeletal Diseases |
| D050723 | Fractures, Bone |
| D014947 | Wounds and Injuries |
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| ID | Term |
|---|---|
| D007052 | Ibuprofen |
| D000068579 | Celecoxib |
| D005480 | Flurbiprofen |
| ID | Term |
|---|---|
| D010666 | Phenylpropionates |
| D000146 | Acids, Carbocyclic |
| D002264 | Carboxylic Acids |
| D009930 | Organic Chemicals |
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4 trial, block randomized crossover design. Three NSAIDs and one placebo trial.
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| Celecoxib 200mg | Drug | Celebrex taken orally 2 hours prior to exercise |
|
|
| Flurbiprofen 100 mg | Drug | Flurbiprofen taken orally 2 hours prior to exercise |
|
|
| Placebo | Drug | Inert placebo taken orally 2 hours prior to exercise |
|
Interlukin-6 (IL-6), Interlukin-10 (IL-10), and tissue necrosis factor (TNF-a) messenger ribonucleic acid (mRNA) concentration in muscle biopsy tissue
| Change from pre-exercise to 3 hours post-exercise |
| Jankowski CM, Shea K, Barry DW, Linnebur SA, Wolfe P, Kittelson J, Schwartz RS, Kohrt WM. Timing of Ibuprofen Use and Musculoskeletal Adaptations to Exercise Training in Older Adults. Bone Rep. 2015 Jan 1;1:1-8. doi: 10.1016/j.bonr.2014.10.003. |
| 20200939 | Background | Kohrt WM, Barry DW, Van Pelt RE, Jankowski CM, Wolfe P, Schwartz RS. Timing of ibuprofen use and bone mineral density adaptations to exercise training. J Bone Miner Res. 2010 Jun;25(6):1415-22. doi: 10.1002/jbmr.24. |
| 33876259 | Background | Wherry SJ, Wolfe P, Schwartz RS, Kohrt WM, Jankowski CM. Ibuprofen taken before exercise blunts the IL-6 response in older adults but does not alter bone alkaline phosphatase or c-telopeptide. Eur J Appl Physiol. 2021 Aug;121(8):2187-2192. doi: 10.1007/s00421-021-04691-8. Epub 2021 Apr 19. |
| 26289996 | Background | Brewer CB, Bentley JP, Day LB, Waddell DE. Resistance exercise and naproxen sodium: effects on a stable PGF2alpha metabolite and morphological adaptations of the upper body appendicular skeleton. Inflammopharmacology. 2015 Dec;23(6):319-27. doi: 10.1007/s10787-015-0248-x. Epub 2015 Aug 20. |
| 30998998 | Background | Park J, Fertala A, Tomlinson RE. Naproxen impairs load-induced bone formation, reduces bone toughness, and diminishes woven bone formation following stress fracture in mice. Bone. 2019 Jul;124:22-32. doi: 10.1016/j.bone.2019.04.009. Epub 2019 Apr 15. |
| D000096926 |
| Benzenesulfonamides |
| D013449 | Sulfonamides |
| D000577 | Amides |
| D001555 | Benzene Derivatives |
| D006841 | Hydrocarbons, Aromatic |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D013450 | Sulfones |
| D013457 | Sulfur Compounds |
| D011720 | Pyrazoles |
| D001393 | Azoles |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D011422 | Propionates |
| D000144 | Acids, Acyclic |
| D001713 | Biphenyl Compounds |