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Nonsteroidal Anti-Inflammatory Drug Prescriptions Are Associated With Increased Stress Fracture Diagnosis in the US Army Population.

ABSTRACT: Stress fractures are common in military personnel and endurance athletes, and nonsteroidal anti-inflammatory drug (NSAID) use is widespread in these populations. NSAIDs inhibit prostaglandin synthesis, which blunts the anabolic response of bone to physical activity and could therefore increase risk of stress fracture. The objective of this study was to determine whether prescribed NSAIDs were associated with stress fracture diagnoses among US Army soldiers. We also aimed to establish whether acetaminophen, an analgesic alternative to NSAIDs, was associated with stress fracture risk. A nested case-control study was conducted using data from the Total Army Injury and Health Outcomes Database from 2002 to 2011 (n?=?1,260,168). We identified soldiers with a diagnosis of stress fracture (n?=?24,146) and selected 4 controls per case matched on length of military service (n?=?96,584). We identified NSAID and acetaminophen prescriptions 180 to 30 days before injury (or match date). We also identified soldiers who participated in basic combat training (BCT), a 10-week period of heightened physical activity at the onset of Army service. Among these individuals, we identified 9088 cases and 36,878 matched controls. Conditional logistic regression was used to calculate incident rate ratios (RR) for stress fracture with adjustment for sex. NSAID prescription was associated with a 2.9-fold increase (RR?=?2.9, 95% confidence interval [CI] 2.8-2.9) and acetaminophen prescription with a 2.1-fold increase (RR?=?2.1, 95% CI 2.0-2.2) in stress fracture risk within the total Army population. The risk was more than 5-fold greater in soldiers prescribed NSAIDs (RR?=?5.3, 95% CI 4.9-5.7) and more than 4-fold greater in soldiers prescribed acetaminophen (RR?=?4.4, 95% CI 3.9-4.9) during BCT. Our results reveal an association between NSAID and acetaminophen prescriptions and stress fracture risk, particularly during periods of heightened physical activity. Prospective observational studies and randomized controlled trials are needed to support these findings before clinical recommendations can be made. © 2018 American Society for Bone and Mineral Research.

SUBMITTER: Hughes JM

PROVIDER: S-EPMC6936225 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature

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Nonsteroidal Anti-Inflammatory Drug Prescriptions Are Associated With Increased Stress Fracture Diagnosis in the US Army Population.

Hughes Julie M JM McKinnon Craig J CJ Taylor Kathryn M KM Kardouni Joseph R JR Bulathsinhala Lakmini L Guerriere Katelyn I KI Popp Kristin L KL Bouxsein Mary L ML Proctor Susan P SP Matheny Ronald W RW

Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research 20181210 3

Stress fractures are common in military personnel and endurance athletes, and nonsteroidal anti-inflammatory drug (NSAID) use is widespread in these populations. NSAIDs inhibit prostaglandin synthesis, which blunts the anabolic response of bone to physical activity and could therefore increase risk of stress fracture. The objective of this study was to determine whether prescribed NSAIDs were associated with stress fracture diagnoses among US Army soldiers. We also aimed to establish whether ace ...[more]

PMID: 30352135

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Project description:ImportanceConcern about the renal effects of nonsteroidand al anti-inflammatory drugs (NSAIDs) among young, healthy adults has been limited, but more attention may be warranted given the prevalent use of these agents.ObjectiveTo test for associations between dispensed NSAIDs and incident acute kidney injury and chronic kidney disease while controlling for other risk factors.Design, setting, and participantsThis retrospective, longitudinal cohort study used deidentified medical and administrative data on 764?228 active-duty US Army soldiers serving between January 1, 2011, and December 31, 2014. Analysis was conducted from August 1 to November 30, 2018. All individuals new to Army service were included in the analysis. Persons already serving in January 2011 were required to have at least 7 months of observable time to eliminate those with kidney disease histories.ExposuresMean total defined daily doses of prescribed NSAIDs dispensed per month in the prior 6 months.Main outcomes and measuresIncident outcomes were defined by diagnoses documented in health records and a military-specific digital system.ResultsAmong the 764?228 participants (655 392 [85.8%] men; mean [SD] age, 28.6 [7.9] years; median age, 27.0 years [interquartile range, 22.0-33.0 years]), 502?527 (65.8%) were not dispensed prescription NSAIDs in the prior 6 months, 137 108 (17.9%) were dispensed 1 to 7 mean total defined daily doses per month, and 124?594 (16.3%) received more than 7 defined daily doses per month. There were 2356 acute kidney injury outcomes (0.3% of participants) and 1634 chronic kidney disease outcomes (0.2%) observed. Compared with participants who received no medication, the highest exposure level was associated with significantly higher adjusted hazard ratios (aHRs) for acute kidney injury (aHR, 1.2; 95% CI, 1.1-1.4) and chronic kidney disease (aHR, 1.2; 95% CI, 1.0-1.3), with annual outcome excesses per 100?000 exposed individuals totaling 17.6 cases for acute kidney injury and 30.0 cases for chronic kidney disease.Conclusions and relevanceModest but statistically significant associations were noted between the highest observed doses of NSAID exposure and incident kidney problems among active young and middle-aged adults.

Project description:BACKGROUND:Lipid transfer protein (LTP), an abundant protein in fruits, vegetables, and nuts, is a common food allergen in Mediterranean areas causing diverse allergic reactions. Approximately 40% of food-related anaphylaxis induced by LTPs requires nonsteroidal anti-inflammatory drugs (NSAIDs) as a triggering cofactor. OBJECTIVE:We sought to better understand the determinants of NSAID-dependent and NSAID-independent LTP-induced anaphylaxis (LTP-A). METHODS:Selection of patients was based on a proved clinical history of NSAID-dependent or NSAID-independent anaphylaxis to LTPs, positive skin prick test response to LTPs, and serum LTP IgE. Whole-transcriptome (RNA sequencing) analysis of blood cells from 14 patients with NSAID-related LTP-A (NSAID-LTP-A), 7 patients with LTP-A, and 13 healthy control subjects was performed to identify distinct gene expression signatures. RESULTS:Expression of genes regulating gastrointestinal epithelial renewal was altered in both patient sets, particularly in those with LTP-A, who also presented with gene expression profiles characteristic of an inflammatory syndrome. These included altered B-cell pathways, increased neutrophil activation markers, and increased reactive oxygen species levels. Increased expression of the IgG receptor (CD64) in patients with LTP-A was mirrored by the presence of LTP-specific IgG1 and IgG3. Conversely, patients with NSAID-LTP-A were characterized by reduced expression of IFN-?-regulated genes and IFN-? levels, as well as upregulated expression of adenosine receptor 3 (ADORA3) and genes related to adenosine metabolism. CONCLUSIONS:Gene ontology analysis suggests disturbances in gut epithelial homeostasis in both groups with LTP-A, with potential integrity breaches in patients with LTP-A that might explain their distinct inflammatory signatures. Differential regulation in patients with LTP-A and those with NSAID-LTP-A of the IFN-? pathway, IgG receptors, and ADORA3 might provide the pathogenic basis of their distinct responses.

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Nonsteroidal Anti-Inflammatory Drug Prescriptions Are Associated With Increased Stress Fracture Diagnosis in the US Army Population.

Publications

Nonsteroidal Anti-Inflammatory Drug Prescriptions Are Associated With Increased Stress Fracture Diagnosis in the US Army Population.

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