Effect of NSAIDs on Bone Healing Rates: A Meta-analysis
Eleven pages on PainSci cite Wheatley 2019: 1. Pain & Injury Survival Tips 2. Icing for Injuries, Tendinitis, and Inflammation 3. The Complete Guide to IT Band Syndrome 4. The Insomnia Guide for Chronic Pain Patients 5. The Complete Guide to Patellofemoral Pain Syndrome 6. The Complete Guide to Muscle Strains 7. Voltaren Gel: Does It Work? 8. Guide to Repetitive Strain Injuries 9. Achilles Tendinitis Treatment Science 10. The Science of Pain-Killers
PainSci notes on Wheatley 2019:
This is a meta-analysis of 16 trials, showing that common over-the-counter pain-killers interfere with bone healing. Chronic overuse roughly doubles the risk that a fracture will heal slowly or not at all (“non-union,” a very serious complication).
The effect was not evident in children or in lower doses or temporary usage — this bad news applies only to adults taking too much of the stuff for too long. Unfortunately, a lot of people do that! The pain-killers in question are the non-steroidal anti-inflammatory drugs or NSAIDs like aspirin, ibuprofen, and naproxen — already notorious for several other significant side effects, and yet still widely overused.
original abstract †Abstracts here may not perfectly match originals, for a variety of technical and practical reasons. Some abstacts are truncated for my purposes here, if they are particularly long-winded and unhelpful. I occasionally add clarifying notes. And I make some minor corrections.
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.
related content
- “Effects of anti-inflammatory (NSAID) treatment on human tendinopathic tissue,” Heinemeier et al, J Appl Physiol (1985), 2017.
- “Oral Ibuprofen Interferes with Cellular Healing Responses in a Murine Model of Achilles Tendinopathy,” Bittermann et al, J Musculoskelet Disord Treat, 2018.
This page is part of the PainScience BIBLIOGRAPHY, which contains plain language summaries of thousands of scientific papers & others sources. It’s like a highly specialized blog. A few highlights:
- Topical glyceryl trinitrate (GTN) and eccentric exercises in the treatment of mid-portion achilles tendinopathy (the NEAT trial): a randomised double-blind placebo-controlled trial. Kirwan 2024 Br J Sports Med.
- Placebo analgesia in physical and psychological interventions: Systematic review and meta-analysis of three-armed trials. Hohenschurz-Schmidt 2024 Eur J Pain.
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- Cannabidiol (CBD) products for pain: ineffective, expensive, and with potential harms. Moore 2023 J Pain.
- Moderators of the effect of therapeutic exercise for knee and hip osteoarthritis: a systematic review and individual participant data meta-analysis. Holden 2023 The Lancet Rheumatology.