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

Hughes, Julie M.; McKinnon, Craig J.; Taylor, Kathryn M.; Kardouni, Joseph R.; Bulathsinhala, Lakmini; Guerriere, Katelyn I.; Popp, Kristin L.; Bouxsein, Mary L.; Proctor, Susan P.; Matheny, Ronald W.

doi:10.1002/jbmr.3616

Cited by 29 publications

(23 citation statements)

References 49 publications

(97 reference statements)

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“…In a case-control study of the entire US Army population between 2002 and 2011, prescribed NSAIDs were associated with a nearly 3-fold increased risk of stress fracture. 21 In this study, soldiers prescribed NSAIDs during rigorous initial military training had a 5.3-fold greater risk for stress fracture compared to soldiers in initial military training who were not prescribed NSAIDs. 21 The increased risk of stress fracture with NSAID prescription during initial military training, a period of heightened physical activity, indicated a significant negative impact of NSAID use on stress fracture risk.…”

Section: Nsaids and Stress Fracture Riskmentioning

confidence: 70%

“…21 In this study, soldiers prescribed NSAIDs during rigorous initial military training had a 5.3-fold greater risk for stress fracture compared to soldiers in initial military training who were not prescribed NSAIDs. 21 The increased risk of stress fracture with NSAID prescription during initial military training, a period of heightened physical activity, indicated a significant negative impact of NSAID use on stress fracture risk. This has important implications for other populations who may increase physical training for athletic and fitness goals.…”

Section: Nsaids and Stress Fracture Riskmentioning

confidence: 70%

“…As NSAIDs are often used for pain relief, studies are also needed to identify potential analgesic substitutes, such as NSAIDs with a nitric oxide donor 71 or acetaminophen, which has been associated with lower stress fracture risk than NSAIDs. 21 Other potentially fruitful lines of research include determining the effects of NSAIDs on the targeted remodeling pathway, establishing the appropriate timing of NSAID administration before or after exercise, and identifying dose-response relationships between various NSAIDs and stress fracture risk. Finally, studies that identify the degree to which NSAIDs inhibit recovery from stress fracture will inform management and treatment algorithms that best support bone repair.…”

Section: Summary and Future Directionsmentioning

confidence: 99%

“…11,12 Other factors thought to predispose individuals to stress fracture include rapid increases in training volume, inherent bone and muscle properties, gait biomechanics, previous exercise history, sustained negative energy intake, and sex hormone and menstrual disturbances. 4,7,[13][14][15] Historical [16][17][18][19] and recent studies 6,20,21 reveal another emerging risk factor for stress fractures-non-steroidal anti-inflammatory drugs (NSAIDs). NSAIDs are some of the most commonly used analgesic drugs in the world.…”

Section: Introductionmentioning

confidence: 99%

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Emerging evidence that adaptive bone formation inhibition by non-steroidal anti-inflammatory drugs increases stress fracture risk

Staab

Kolb

Tomlinson

et al. 2021

Exp Biol Med (Maywood)

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There is mounting evidence suggesting that the commonly used analgesics, non-steroidal anti-inflammatory drugs (NSAIDs), may inhibit new bone formation with physical training and increase risk of stress fractures in physically active populations. Stress fractures are thought to occur when bones are subjected to repetitive mechanical loading, which can lead to a cycle of tissue microdamage, repair, and continued mechanical loading until fracture. Adaptive bone formation, particularly on the periosteal surface of long bones, is a concurrent adaptive response of bone to heightened mechanical loading that can improve the fatigue resistance of the skeletal structure, and therefore may play a critical role in offsetting the risk of stress fracture. Reports from animal studies suggest that NSAID administration may suppress this important adaptive response to mechanical loading. These observations have implications for populations such as endurance athletes and military recruits who are at risk of stress fracture and whose use of NSAIDs is widespread. However, results from human trials evaluating exercise and bone adaptation with NSAID consumption have been less conclusive. In this review, we identify knowledge gaps that must be addressed to further support NSAID-related guidelines intended for at-risk populations and individuals.

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Section: Nsaids and Stress Fracture Riskmentioning

confidence: 70%

Section: Nsaids and Stress Fracture Riskmentioning

confidence: 70%

Section: Summary and Future Directionsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Emerging evidence that adaptive bone formation inhibition by non-steroidal anti-inflammatory drugs increases stress fracture risk

Staab

Kolb

Tomlinson

et al. 2021

Exp Biol Med (Maywood)

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“…Thus, runners seem to obtain some benefit from NSAIDs, 28 but there is concern for SF and other bone injuries. A study by Hughes et al 29 found that NSAID prescription increased risk for SFs more than 3-fold in soldiers during periods of regular activity and more than 5-fold during periods of more heightened physical activity. These results are believed to be due to de- creased bone anabolism in response to loading after taking NSAIDS, possibly due to attenuation of prostaglandin production.…”

Section: Discussionmentioning

confidence: 99%

Risk Factors for Stress Fractures in Female Runners: Results of a Survey

Johnston

Jakavick

Mancuso

et al. 2021

International Journal of Sports Physical Therapy

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Background BackgroundFew studies compare women with and without stress fractures and most focus on younger, elite runners. Hypothesis/Purpose Hypothesis/PurposeCompare risk factors between female runners with and without a stress fracture history. Study Design Study DesignCase control Methods MethodsAn online survey targeting women age ≥18 years was distributed primarily via social media. Questions included demographics, running details, cross training, nutrition, injury history, medical/menstrual history, and medications. Women with stress fracture histories answered questions about location, number, and changes made. Data were compared between groups using t-tests, chi-square tests, or Fisher's exact tests. Multivariable logistic regression models simultaneously investigated associations of multiple factors using backward variable selection. Results ResultsData from 1648 respondents were analyzed. Mean age was 40 years, and 25.4% reported stress fractures. Significant differences were found between groups for days/week running, mileage/week, running pace, years running, having a coach, cycling or swimming, calorie consumption for activity, other running injuries, medical history, medication/supplement intake, age at menarche, and going ≥6 months without a menstrual period. Odds of having a stress fracture were increased with osteopenia (OR 4.14), shin splints (OR 3.24), tendon injuries (OR 1.49), running >20 miles/week (OR 1.74-1.77) compared to 11-20 miles/week, having a coach (OR 1.86), and cycling (OR 1.15). Women running 11:00-11:59 minutes/mile or slower were less likely to have a stress fracture compared to those running 9:00-9:59 minutes/mile (OR 0.43-0.54). The odds of having a stress fracture were 1.43 times higher for going ≥ 6 months without a menstrual period. Use of calcium, probiotics, and vitamin D increased odds. Post fracture, common changes made were with cross training (49%), mileage (49%), and strength training (35%). Conclusions ConclusionsMultiple intrinsic and extrinsic factors were identified for female runners who sustained one or more stress fracture during running. Prospective studies are warranted to infer a cause and effect relationship amongst these variables and stress fracture risk.

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