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Cited by 155Inflammatory mediators and NSAID effectsBone Metabolism and DiseasesBone fractures and treatments

The DOI matches its Crossref record; 60 of the 60 references it cites were found in a registry or an index.

The Mechanisms of the Inhibitory Effects of Nonsteroidal Anti‐Inflammatory Drugs on Bone Healing: A Concise Review

Harder, Adam T., An, Yuehuei H.·2003·The Journal of Clinical Pharmacology
DOI 10.1177/0091270003256061
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Abstract

Nonsteroidal anti-inflammatory drug (NSAID) use continues to expand at a remarkable rate due both to the broad spectrum of clinical applications for these medications and to the relatively recent introduction of the popular COX-2-selective inhibitors. The use of NSAIDs is particularly prevalent in patients with a variety of musculoskeletal conditions and injuries. Reports of impaired bone healing associated with NSAID use, therefore, are a particular cause for concern. Animal and in vitro studies have demonstrated impaired bone healing in the presence of traditional NSAIDs, as measured by a variety of different parameters. More recently, initial studies investigating the effects of COX-2-selective inhibitors on bone healing have yielded similar results. With mounting evidence that NSAIDs do in fact interfere with proper bone healing in various animal models, questions have arisen regarding the potential mechanism through which NSAIDs produce this outcome and whether these results can be translated to clinical settings. A likely pathway for these observed effects results from an understanding of the steps involved in bone healing itself. These steps include an inflammatory response, bone resorption, and new bone formation. Investigations over the past several decades have elucidated a role for prostaglandins (PGs) in each of these areas. Specifically, PGs have been shown to elicit and participate in inflammatory responses, increase osteoclast activity and subsequent bone resorption, and increase osteoblast activity and new bone formation. This apparent integral role for PGs in the process of bone healing, coupled with the knowledge that NSAIDs act by inhibiting the production of PGs, results in an understanding of the likely mechanism through which NSAIDs impart their deleterious effects on bone healing. By inhibiting the COX enzymes and the subsequent production of PGs, NSAIDs not only achieve their desired anti-inflammatory effects but also inhibit the increased production of PGs that is necessary for bone healing to occur. Despite this understanding of the potential mechanism through which NSAIDs inhibit bone healing in a laboratory setting, few studies exist that show whether these inhibitory effects are also evident clinically. Thus, further studies will need to decipher whether similar inhibitory effects occur in a clinical setting.

Overview

Integrity signals

Registry

Crossref · 10.1177/0091270003256061

Cites

60 of 60 references verified0 citation errors · 0 not checkable

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Citations

Cites

1 retracted

Research works printed but not linked: 5

  1. Katzung BG, 1998, Pharmacology
  2. 1981, National Disease and Therapeutic Index
  3. Kumar V, 1997, Basic Pathology
  4. High W, 1989, Effects of prostaglandin E2 on fracture healing in adult dogs, J Bone Miner Res, 4, 404S
  5. Schelling SH, 1980, Role of the osteoclast in prostaglandin E2‐stimulated bone resorption, Lab Invest, 42, 290

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Metadata

Authors
Harder, A. T., & An, Y. H.
Affiliations
Medical University of South Carolina (US)
Corresponding author
An, Yuehuei H.
Venue
The Journal of Clinical Pharmacology
Publisher
Wiley
Published
2003-08
Volume
43
Issue
8
Pages
807-815
ISSN
  • 0021-9754 (ISSN-L)
  • 0091-2700
  • 1552-4604
DOI
10.1177/0091270003256061
OpenAlex
W1966052052
Cited by
155
References
59
Citations by year
2026: 2 · 2025: 4 · 2024: 2 · 2023: 6 · 2022: 4 · 2021: 6 · 2020: 5 · 2019: 7 · 2018: 7 · 2017: 10 · 2016: 9 · 2015: 5 · 2014: 10 · 2013: 4 · 2012: 6
FWCI
0.87
Type
journal article
Language
en
Open access
closed
Licence
onlinelibrary.wiley.com/termsAndConditions#vor (vor, 3507 d)
Locations
  • The Journal of Clinical Pharmacology (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Pharmacology (medical) › Inflammatory mediators and NSAID effects
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bone Metabolism and Diseases
  • Health Sciences › Medicine › Orthopedics and Sports Medicine › Bone fractures and treatments
Keywords
nonsteroidal anti-inflammatory drugs, bone regeneration, COX-2 inhibitors, prostaglandins, bone resorption, osteoclasts, osteoblasts, inflammation, fracture healing
MeSH terms
Animals, Anti-Inflammatory Agents, Non-Steroidal, Bone and Bones, Humans, Wound Healing, Cyclooxygenase Inhibitors

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Data sources

Bibliographic data: Semantic Scholar, OpenAlex, Crossref.

Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).

Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.