Introduction
Up to 100,000 fractures do not heal properly each year; either through nonunion, delayed union, or symptomatic pseudarthrosis. These instances may cause complications such as additional surgeries, pain, prolonged immobilization, increased physician visits which can all be time consuming and expensive. There are multiple risk factors that have been identified as possibly affecting the rate of bone healing. Older age, female sex, fracture characteristics, fracture location, and patient co-morbidities are nonmodifiable risk factors. Some of the many modifiable risk factors are alcohol and tobacco consumption, nutritional status, and medications. Nonsteroidal Anti-inflammatory drugs (NSAIDs) are one of the medications thought to effect bone healing, but past research has been controversial.
How are NSAIDs thought to effect bone healing?
Prostaglandins are believed to play a part in bone healing and metabolism because the concentration of Prostaglandin E2 (PGE2) is thought to control osteoblast behavior through the relative expression of the receptor activator of nuclear factor kappa-B ligand and osteoprotegerin. These are regulated through the enzymes cyclooxygenase (COX)-1 and (COX)-2 which are inhibited by NSAIDs. This inhibition causes a decreased in PGE2 which is thought to cause the delayed bone healing.
In the article titles: Effect of NSAIDs on Bone Healing Rates: A Meta-analysis; the authors analyzed 16 research articles to determine the whether the use of NSAIDs increased the risk of delayed union or nonunion after a fracture, osteotomy, or fusion surgery.
The articles were all analyzed together as well as in subgroups. The following conclusions were made by the authors:
- Analyzing all studies together; without subgroups
- NSAIDs increased the risk of delayed union or nonunion healing.
- Subgroup: only studies including pediatric studies
- NSAIDs did not result in an increased risk of delayed union or nonunion healing.
- Limitations: Small study pool (4 studies)
- Subgroup: only studies including adult studies
- NSAIDs increased the risk of delated union or nonunion healing
- Subgroup: adult only with long bone involvement
- NSAIDs increased the risk of delated union or nonunion healing
- Subgroup: adult only with spine involvement
- NSAIDs increased the risk of delated union, nonunion healing, or pseudarthrosis
- Limitations: Small study pool (5 studies)
- Subgroup: low dose NSAIDs or short duration of NSAID use
- Low dose was defined as <125 mg/d of diclofenac, 150 mg/d of indomethacin, or 120 mg/d of ketorolac.
- Short duration was defined as <2 weeks of NSAID use.
- NSAIDs did not result in an increased risk of delayed union or nonunion healing.
- Limitations: Small study pool (4 studies) and inconsistent findings between studies (2 found an increased risk while the other 2 found no effect).
- Author thoughts:
- For lower dose NSAIDs, the authors believed that there may be less potency and/or less prosoglandin suppression which may allow fracture healing to continue at a slower rate
- For short duration, the authors believed the bone healing is able to continue as usual after withdrawal of NSAIDs.
Limitations
- As mentioned earlier, there are multiple factors that contribute to bone healing, with age being one of them. In the study, the authors found the effect of NSAIDs on delayed union or nonunion was directly related to patient age. Therefore, it is difficult to determine if the age of study participants also played a role in the results. The authors stated age was difficult to analyze as a continuous variable due to there being a large age gap between the ages of 18 to 35 years throughout the studies and the mean age of adult studies being on the higher end.
- Limited availability of randomized control trials
- Heterogeneity (diversity of subjects) of analyzed studies made them difficult to compare
For more information regarding this topic or the research presented, please see the article referenced below. Here at physical therapy first, we understand how unique everyone’s rehabilitation is. When starting care here, you will begin with an initial evaluation in order to determine an individualized rehabilitative program for you. Give us a call or visit the website to schedule an appointment!
Reference:
Wheatley BM, Nappo KE, Christensen DL, Holman AM, Brooks DI, Potter BK. Effect of NSAIDs on Bone Healing Rates: A Meta-analysis. J Am Acad Orthop Surg. 2019 Apr 1;27(7):e330-e336. doi: 10.5435/JAAOS-D-17-00727. PMID: 30260913.