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Effect of NSAIDs on Bone Healing Rates: A Meta-analysis

Wheatley, Benjamin M. MD; Nappo, Kyle E. MD; Christensen, Daniel L. MD; Holman, Ann M. MLS; Brooks, Daniel I. PhD; Potter, Benjamin K. MD

JAAOS - Journal of the American Academy of Orthopaedic Surgeons: April 1, 2019 - Volume 27 - Issue 7 - p e330-e336
doi: 10.5435/JAAOS-D-17-00727
Research Article

Introduction: NSAIDs inhibit osteogenesis and may result in delayed union or nonunion. The purpose of this meta-analysis was to determine whether their use leads to delayed union or nonunion.

Methods: We systematically reviewed the literature reporting the effect of NSAIDs on bone healing. We included studies of pediatric and adult patients NSAID exposure and healing bone. The outcomes of interest were delayed union, nonunion, or pseudarthrosis with at least six months of follow-up. A maximum likelihood random-effects model was used to conduct meta-analysis and meta-regression.

Results: NSAID exposure increased delayed union or nonunion (odds ratio [OR], 2.07; confidence interval [CI], 1.19 to 3.61). No effect was noted in pediatrics (OR, 0.58; CI, 0.27 to 1.21) or low dose/short duration of exposure (OR, 1.68; CI, 0.63 to 4.46).

Conclusion: Analysis of the literature indicates a negative effect of NSAIDs on bone healing. In pediatric patients, NSAIDs did not have a significant effect. The effect may be dose or time dependent because low-dose/short-duration exposure did not affect union rates.

From the Division of Orthopaedic Surgery (Dr. Wheatley, Dr. Nappo, Dr. Christensen, and Dr. Potter), Uniformed Services University, Walter Reed Department of Surgery, the Darnall Medical Library (Ms. Holman), Walter Reed National Military Medical Center, and the Department of Research Programs (Dr. Brooks), Walter Reed National Military Medical Center, Bethesda, MD.

Correspondence to Dr. Potter:

Dr. Christensen or an immediate family member has stock or stock options held in Conformis. Dr. Potter or an immediate family member serves as an unpaid consultant to Zimmer Biomet and serves as a board member, owner, officer, or committee member of the Society of Military Orthopaedic Surgeons. None of the following authors nor any immediate family member has received anything of value from or has stock or stock options held in a commercial company or institution related directly or indirectly to the subject of this article: Dr. Wheatley, Dr. Nappo, Ms. Holman, and Dr. Brooks.

Written work prepared by employees of the Federal Government as part of their official duties is, under the U.S. Copyright Act, a “work of the United States Government” for which copyright protection under Title 17 of the United States Code is not available. As such, copyright does not extend to the contributions of employees of the Federal Government.
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