The Effects of NSAIDs on Bone Metabolism Following Exercise

Bone Resorption Clinical Trial

Official title:

The Effects of Non-steroidal Anti-inflammatory Drugs on Circulating Markers of Bone Metabolism Following Plyometric Exercise in Humans

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05512013
• Other study ID #: 21-18H
• Status: Completed
• Phase: Phase 1
• Start date: February 15, 2022
• Est. completion date: April 1, 2023

Study information

• Verified date: November 2023
• Source: United States Army Research Institute of Environmental Medicine
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 12
• Est. completion date: April 1, 2023
• Est. primary completion date: April 1, 2023
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 42 Years

Eligibility

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

Related Conditions & MeSH terms

• Bone Injury
• Bone Resorption
• Fractures, Stress
• Stress Fracture

Intervention

Drug:
• Ibuprofen 800 mg
Ibuprofen taken orally 2 hours prior to exercise
• Celecoxib 200mg
Celebrex taken orally 2 hours prior to exercise
• Flurbiprofen 100 mg
Flurbiprofen taken orally 2 hours prior to exercise
• Placebo
Inert placebo taken orally 2 hours prior to exercise

Locations

Country	Name	City	State
United States	United States Army Research Institute of Environmental Medicine	Natick	Massachusetts

Sponsors (1)

Lead Sponsor	Collaborator
United States Army Research Institute of Environmental Medicine

Country where clinical trial is conducted

United States, 

References & Publications (6)

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. — View 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. — View 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. — View 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. — View 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. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Muscle protein synthesis	ribosomal protein S6 (p-RPS6) protein concentration in muscle biopsy tissue	Change from pre-exercise to 3 hours post-exercise
Primary	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
Secondary	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
Secondary	Markers of muscle inflammation	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