The Effects of NSAIDs on Bone Metabolism Following Exercise

Phase 1

Completed

• Conditions: Bone Resorption; Stress Fracture; Bone Injury
• Interventions: Drug: Ibuprofen 800 mg; Drug: Flurbiprofen 100 mg; Drug: Celecoxib 200mg; Drug: Placebo

• Registration Number: NCT05512013
• Lead Sponsor: United States Army Research Institute of Environmental Medicine

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.

Study Timeline

• Study Start: 2022-02-15
• Study First Submitted: 2022-08-16
• Study First Submitted QC: 2022-08-19
• Study First Posted: 2022-08-23
• Primary Completion: 2023-04-01
• Study Completion: 2023-04-01
• Status Verified: 2023-11
• Last Update Submitted: 2023-11-28
• Last Update Posted: 2023-11-29

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 12

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

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Ibuprofen	Ibuprofen 800 mg	Participants will consume a single dose of ibuprofen prior to a plyometric exercise bout
Flurbiprofen	Flurbiprofen 100 mg	Participants will consume a single dose of flurbiprofen prior to a plyometric exercise bout
Celecoxib	Celecoxib 200mg	Participants will consume a single dose of celecoxib prior to a plyometric exercise bout
Placebo	Placebo	Participants will consume a single dose of an inert placebo prior to a plyometric exercise bout

Primary Outcome Measures

Name	Time	Method
Change from baseline circulating marker of bone formation	Change from pre-exercise to 4 hours post-exercise	Concentration (pg/mL) of serum N-terminal propeptide of type 1 collagen (P1NP)

Secondary Outcome Measures

Name	Time	Method
Change from baseline circulating marker of bone resorption	Change from pre-exercise to 4 hours post-exercise	Concentration (pg/mL) of serum C-terminal propeptide of type I collagen (CTX)
Markers of muscle inflammation	Change from pre-exercise to 3 hours post-exercise	Interlukin-6 (IL-6), Interlukin-10 (IL-10), and tissue necrosis factor (TNF-a) messenger ribonucleic acid (mRNA) concentration in muscle biopsy tissue

Trial Locations

Locations (1)

United States Army Research Institute of Environmental Medicine; 🇺🇸 Natick, Massachusetts, United States