Dataset Information

The Effect of Nonsteroidal Anti-inflammatory Drugs and Selective COX-2 Inhibitors on Bone Healing.

ABSTRACT: A recently published study, "Risk of Nonunion With Nonselective NSAIDs, COX-2 Inhibitors, and Opioids" by George et al (J Bone Joint Surg Am. 2020;102:1230-1238), assesses whether the use of nonselective nonsteroidal anti-inflammatory drugs (NSAIDs), selective cyclooxygenase 2 (COX-2) enzyme inhibitors, or opioids was associated with a risk of long bone fracture nonunion in Optum's deidentified private health database. This review analyzes the study, including strengths, weaknesses, and areas for future research. The study found an association between COX-2 inhibitor and opioid use with fracture nonunion but not with nonselective NSAID use. Although the literature on this topic is varied, these results are at least partially aligned with several animal studies that show COX-2 inhibitors to be associated with fracture nonunion. The George et al study design has several important limitations, indicating that further research is needed on this topic.

SUBMITTER: White AE

PROVIDER: S-EPMC8361590 | biostudies-literature | 2021 Jul

REPOSITORIES: biostudies-literature

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The Effect of Nonsteroidal Anti-inflammatory Drugs and Selective COX-2 Inhibitors on Bone Healing.

White Alexander E AE Henry Jensen K JK Dziadosz Daniel D

HSS journal : the musculoskeletal journal of Hospital for Special Surgery 20210320 2

A recently published study, "Risk of Nonunion With Nonselective NSAIDs, COX-2 Inhibitors, and Opioids" by George et al (<i>J Bone Joint Surg Am.</i> 2020;102:1230-1238), assesses whether the use of nonselective nonsteroidal anti-inflammatory drugs (NSAIDs), selective cyclooxygenase 2 (COX-2) enzyme inhibitors, or opioids was associated with a risk of long bone fracture nonunion in Optum's deidentified private health database. This review analyzes the study, including strengths, weaknesses, and a ...[more]

PMID: 34421436

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Project description:BackgroundDifferences between gastrointestinal and cardiovascular effects of traditional NSAID or cyclooxygenase-2 selective inhibitor (coxib) are affected by drug, dose, duration, outcome definition, and patient gastrointestinal and cardiovascular risk factors. We calculated the absolute risk for each effect.MethodsWe sought studies with large amounts of information to calculate annualised rates for clearly defined gastrointestinal (complicated upper gastrointestinal perforations, ulcers, or bleeds, but not symptomatic or endoscopic ulcers) and serious cardiovascular outcomes (antiplatelet trial collaborators - APTC - outcome of fatal or nonfatal myocardial infarction or stroke, or vascular death).ResultsMeta-analyses and large randomised trials specifically analysing serious gastrointestinal bleeding or cardiovascular events occurring with five different coxibs had appropriate data. In total there were 439 complicated upper gastrointestinal events in 49,006 patient years of exposure and 948 serious cardiovascular events in 99,400 patient years of exposure. Complicated gastrointestinal events occurred less frequently with coxibs than NSAIDs; serious cardiovascular events occurred at approximately equal rates. For each coxib, the reduction in complicated upper gastrointestinal events was numerically greater than any increase in APTC events. In the overall comparison, for every 1000 patients treated for a year with coxib rather than NSAID, there would be eight fewer complicated upper gastrointestinal events, but one more fatal or nonfatal heart attack or stroke. Three coxib-NSAID comparisons had sufficient numbers of events for individual comparisons. For every 1000 patients treated for a year with celecoxib rather than an NSAID there would be 12 fewer upper gastrointestinal complications, and two fewer fatal or nonfatal heart attacks or strokes. For rofecoxib there would be six fewer upper gastrointestinal complications, but three more fatal or nonfatal heart attacks or strokes. For lumiracoxib there would be eight fewer upper gastrointestinal complications, but one more fatal or nonfatal heart attack or stroke.ConclusionCalculating annualised event rates for gastrointestinal and cardiovascular harm shows that while complicated gastrointestinal events occur more frequently with NSAIDs than coxibs, serious cardiovascular events occur at approximately equal rates. For each coxib, the reduction in complicated upper gastrointestinal events was numerically greater than any increase in APTC events.

Project description:BackgroundNonsteroidal anti-inflammatory drugs (NSAIDs) are commonly used to mitigate pain and inflammation associated with musculoskeletal conditions; however, there is conflicting data on the adverse effects of these drugs on tissue and bone healing. The objective of this study was to investigate the effect of NSAIDs on the healing of knee, soft tissue, and bone.MethodsA systematic literature search was conducted across PubMed/MEDLINE, Excerpta Medical Database (Embase)/Ovid, and the Cochrane Central Register of Controlled Trials databases. Clinical, animal, and in vitro studies on the effect of NSAIDs on knee healing were included. Risk of bias assessment was performed using the Cochrane bias assessment tool and Methodological Index for Non-Randomized Studies scoring system for included clinical studies, and the Systematic Review Center for Laboratory Animal Experimentation assessment tool for all included animal studies. General study population characteristics, interventions used, NSAIDs utilized, outcome measures, and study results were analyzed using descriptive statistics.ResultsFifteen articles met the inclusion criteria. Of the 15 studies, there were three clinical, ten animal, and two in vitro studies. In clinical studies, nonselective cyclooxygenase (COX) inhibitors and selective COX-2 inhibitors did not cause a significant increase in failure of anterior cruciate ligament (ACL) reconstructions or meniscal repairs with NSAID administration pre-, peri-, or post-operatively in comparison to placebo or no NSAID administration. Among animal studies assessing COX-2 inhibitor effects on soft tissue, healing was impaired (2/4), delayed but unaffected (1/4), or unaffected (1/4). In animal studies assessing COX-1 inhibitors, ligament healing was either increased (1/4), unaffected (2/4), or impaired (1/4). Meanwhile, administration of non-selective COX inhibitors in animals did not affect soft tissue (3/3) and cartilage (1/1) healing. Two in vitro studies identified a negative outcome on patellar tendon and ACL cell proliferation or viability after non-selective COX inhibition and variable results after selective COX-2 inhibition.ConclusionsAnimal studies on postoperative NSAID use after knee surgery suggest that administration of selective and nonselective COX-2 inhibitors may impair healing of soft tissue, bone and tendon-to-bone; however, further clinical studies are needed to better characterize dose and duration dependent risks of NSAIDs.

Project description:Background and objectivesThere have been doubts about the association between nonsteroidal anti-inflammatory drug use and worsening kidney function, and whether there is a difference between risks of individual nonsteroidal anti-inflammatory drugs is presently unclear. Therefore, this study aimed to evaluate the association between nonsteroidal anti-inflammatory drug exposure and the risk of incident eGFR <60 ml/min per 1.73 m2 and compare the risks between nonsteroidal anti-inflammatory drug subtypes in the Chinese population.Design, setting, participants, & measurementsFrom 2008 to 2017, a total of 1,982,488 subjects aged 18 years or older with baseline eGFR ≥60 ml/min per 1.73 m2 were enrolled in this retrospective cohort study. Multivariable Cox proportional hazards regression adjusted for each patient's baseline characteristics was adopted to examine the association between nonsteroidal anti-inflammatory drug and incident eGFR <60 ml/min per 1.73 m2 or eGFR decline ≥30% with reference to baseline.ResultsAfter a median follow-up duration of 6.3 (interquartile range, 3.3-9.4) years, 271,848 cases (14%) of incident eGFR <60 ml/min per 1.73 m2 and 388,386 (21%) events of eGFR decline ≥30% were recorded. After adjusting for each patient's baseline characteristics, nonsteroidal anti-inflammatory drug treatment was shown to be associated with a significantly higher risk of incident eGFR <60 ml/min per 1.73 m2 (hazard ratio, 1.71; 95% confidence interval, 1.67 to 1.75) and eGFR decline ≥30% (hazard ratio, 1.93; 95% confidence interval, 1.89 to 1.96) when compared with no nonsteroidal anti-inflammatory drug, with etoricoxib exhibiting the highest risk of eGFR<60 ml/min per 1.73 m2 (hazard ratio, 3.12; 95% confidence interval, 2.69 to 3.62) and eGFR decline ≥30% (hazard ratio, 3.11; 95% confidence interval, 2.78 to 3.48) and ibuprofen displaying the lowest risk of eGFR<60 ml/min per 1.73 m2 (hazard ratio, 1.12; 95% confidence interval, 1.02 to 1.23) and eGFR decline ≥30% (hazard ratio, 1.32; 95% confidence interval, 1.23 to 1.41).ConclusionsNonsteroidal anti-inflammatory drug exposure was associated with higher risks of incident eGFR <60 ml/min per 1.73 m2 and eGFR decline ≥30%. Highest risk was observed in etoricoxib users, and lowest risk was with ibuprofen.PodcastThis article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2021_04_28_CJN18501120.mp3.

Dataset Information

The Effect of Nonsteroidal Anti-inflammatory Drugs and Selective COX-2 Inhibitors on Bone Healing.

Publications

The Effect of Nonsteroidal Anti-inflammatory Drugs and Selective COX-2 Inhibitors on Bone Healing.

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