The effect of nonsteroidal anti-inflammatory drugs on
tissue healing.

Chen MR, and Gragoo
JL. Knee Surg Sports Traumatol Arthrosc. 2012; [Epub ahead of print].

(NSAIDS) and selective (COX-2 inhibitors) nonsteroidal anti-inflammatory drugs
are often used during the inflammatory stage of healing because of their
analgesic and anti-inflammatory properties. The use of these drugs, especially
following surgery, is controversial because some pathways of tissue healing may
be disrupted by the drugs in an attempt to gain the desired effect. Therefore,
Chen and Gragoo performed a review of literature to assess the evidence of an
effect of NSAIDS and COX-2 inhibitors on soft tissue and bone healing. The
authors performed a MEDLINE search using the following keywords: “nonsteroidal
anti-inflammatory or cyclooxygenase 2 inhibitor and bone, fracture, tendon, or
ligament and healing.” Studies were excluded if the studied drug, a) was not
available for patients in the United States, b) had only 1 animal study, and c)
was only assessed in an in vitro study or did not examine fracture healing.
Initially, they identified 637 articles but following removal of duplicate
findings and applying the exclusion criteria a total of 44 studies (9 soft
tissue, 35 bone healing; 39 animal, 5 human studies) were analyzed. With
respect to soft tissue healing, the authors identified 3 medications with
enough detail for analysis: indomethacin, piroxicam, and celecoxib. Analysis
revealed that both indomethacin and celecoxib had insufficient evidence to
determine their effects on soft tissues healing; however, piroxicam showed no
detrimental effect on soft tissue healing. Three studies also looked at indomethacin
and celecoxib but with respect to soft tissue-to-bone healing. All of these
studies reported a detrimental effect on soft tissue-to-bone healing. Finally,
29 studies observed bone healing in both animal and human models and identified
7 different drugs (indomethacin, ketorolac, celecoxib, ibuprofen, diclofenac, piroxicam,
“NSAID exposure”). Of these 29 studies only 1 study found any type of
beneficial influence of anti-inflammatory drugs on bone healing, while 32
studies found the effects to be either “no effect” (10), “no
effect/detrimental” (7) or “detrimental” (15). Among these, indomethacin was
suggested to be detrimental to bone healing while piroxicam had evidence that
it was not.

Overall, this review
concluded that the short-term, low dose use of anti-inflammatory medications is
prudent in treatment of sports medicine injuries and following surgery, but
should be avoided if bone healing is needed. While these results seem simple
one must be cautious when deciphering them since the studies included animal
models and human models. Further compounding the results is that the animal
model studies used various animals (rabbits, mice and rats) and evaluated varying
drug dosages. Therefore, a true comparison of the studies’ results was extremely
difficult. With that being said, this does seem to support the current clinical
practice of recommending short-term, low dose use anti-inflammatory medications
to athletes who have suffered soft tissue injuries. In cases where clinicians
are advising patients following surgery, care should be taken to identify what
was done during the procedure to adequately advise patients as certain anti-inflammatory
medications seemed to have a detrimental effect on bone healing. Tell us what
you have found when recommending anti-inflammatory medications to your
patients. Where do you get your dosage recommendations? How much does the
specifics of the injury play a role in your decision whether or not to
recommend anti-inflammatory drugs?

Written by: Kyle
Reviewed by:  Jeffrey Driban

SMR Note: SMR does
not traditionally provide posts for critical or narrative reviews but since
this topic often comes up in discussion we felt it was appropriate to have a
post. Please keep in mind that narrative reviews are not the same level of
evidence as a systematic review. 

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Chen MR, & Dragoo JL (2012). The effect of nonsteroidal anti-inflammatory drugs on tissue healing. Knee Surgery, Sports Traumatology, Arthroscopy PMID: 22744434