Clinical trial NCT05512013: The Effects of NSAIDs on Bone Metabolism Following Exercise
Official title: The Effects of Non-steroidal Anti-inflammatory Drugs on Circulating Markers of Bone Metabolism Following Plyometric Exercise in Humans
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Bone Resorption
Stress Fracture
Bone Injury
Lead sponsor: United States Army Research Institute of Environmental Medicine
Sponsor class: FED
First posted: 2022-08-23
Enrollment: 12
Sex: ALL
Minimum age (years): 18
Maximum age (years): 42
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: 4 trial, block randomized crossover design. Three NSAIDs and one placebo trial.
Primary purpose: BASIC_SCIENCE

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

* Must currently exercise at least 2 times per week
* Must be willing to discontinue the use of nutritional supplements, alcohol and nicotine during each study period (4 trials of 5 consecutive days each), unless approved by PI
* Must be willing to refrain from taking NSAIDs and similar medications during the course of the study (other than those given by the study team)
* Weigh at least 110 lbs and have a hemoglobin of 12.5 g/dL or higher

Exclusion Criteria:

* Known allergic reaction to any NSAID type medication
* History of gastrointestinal disorders/discomfort associated with or which may be aggravated with NSAID use
* History or known gastric ulcer
* History of endocrine disorders (e.g., diabetes, uncontrolled thyroid dysfunction, hypoparathyroidism, or hyperparathyroidism)
* History of bone-modifying disorder (e.g., osteogenesis imperfecta, osteoporosis, or rickets)
* Diagnosed bone fracture within last 6 months
* History of cardiovascular or renal diseases
* Pregnant or lactation in the last 6 months
* Currently taking or history of routine use of medications known to affect bone or calcium metabolism (e.g., thiazide diuretics, bisphosphonates, oral steroids)
* History of back or shoulder injury which may be aggravated by exercise
* Blood donation within 8 weeks of the study
* Current physical illness or injury limiting physical activity
* Known allergy to lidocaine

Primary outcomes:
measure: Change from baseline circulating marker of bone formation
timeFrame: Change from pre-exercise to 4 hours post-exercise
Secondary outcomes:
measure: Change from baseline circulating marker of bone resorption
timeFrame: Change from pre-exercise to 4 hours post-exercise
measure: Markers of muscle inflammation
timeFrame: Change from pre-exercise to 3 hours post-exercise
Other outcomes:
measure: Muscle protein synthesis
timeFrame: Change from pre-exercise to 3 hours post-exercise
Locations:
city: Natick
country: United States
facility: United States Army Research Institute of Environmental Medicine
state: Massachusetts
Study officials:
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.