Ibuprofen may not be a runner’s friend.

**I must preface this blog by stating that I am not a physician or medical doctor, but am well versed in medical and scientific research as it applies to a population (as opposed to an individual). I received my Master’s of Public Health from Brown University in the field of Epidemiology and Public Policy. I am currently at UAB, working on my doctoral dissertation in the field of the epidemiology of dengue fever in the Americas. Note that neither of these are sports-related. Also note that this is a VERY brief review. I spent all of an hour searching for articles and another hour typing this up. I just wanted to very briefly share the following information with my fellow athletes. If you have an injury, you’ll now be a little more informed when asking your doctor what meds you should take during your recovery and rehab.
Small note: the lovely Meg has pointed out to me that there is some confusion among experts as to whether acetaminophen (aka paracetamol or Tylenol) is or is not an NSAID. For the purposes of this blog, I am considering acetaminophen an NSAID, as it has the same effect on prostaglandin.

In my crew days back in college, I took a lot of ibuprofen. My doctor advised me that I could take up to 2400mg a day, usually 800mg ever six hours, for 10-14 days for an acute injury and do no damage to my system. In fact, she encouraged it, stating that ibuprofen reduces inflammation which leads to faster healing. There is plenty of evidence stating that NSAIDs (non-steroidal anti-inflammatory drugs, such as acetaminophen (Tylenol), ibuprofen (Advil, Motrin) and naproxen (Aleve)) are a wonderful component for recovery from soft tissue or muscular damage, which I’m sure you all already know.

Unfortunately, and completely unknown to even me before this year (a self-admitted addict when it comes to knowing about things like this), there is increasing evidence suggesting that NSAIDs, especially ibuprofen might actually inhibit bone, tendon and ligament healing. Here, I’ll present to you some over-all themes, but as I do, keep in mind these two facts: (1) animal studies may be more easily controlled, but it’s hard to transfer information from a rat to a human and (2) current human studies have a lot of issues due to confounding factors.

**Warning: Public Health Lesson** What are confounding factors? These are factors that might hide a real link between an exposure and an outcome. Let me give you an example. If you knew nothing about cigarettes, you could theoretically (but wrongly) argue that alcohol causes lung cancer. Think about it: people who drink are more likely to smoke or be at bars around people who smoke; people who smoke or are often around smoke get lung cancer. If you’d never heard of cigarettes, you wouldn’t know to measure for them, leading to your false assumption. So in the case of NSAIDs increasing the risk of fracture, there could be something that we’re missing, a random hypotheses that comes to mind is people who have more muscle pain – and therefore take more NSAIDs – are more likely to get fractures because their muscles are less flexible, which puts more stress on bones leading to and reducing healing in a stress fracture. So in this case, the NSAID use itself wouldn’t be the cause, they’d just be correlated.  “Correlation does not equal causation” is a phrase thrown around a lot in public health.

Now on to the current body of evidence:

Results from animal studies show that NSAIDs may adversely affect fracture healing. This suggests that taking an NSAID after a fracture has occurred appear to lead to an increase in healing time:

“Animal studies have shown that NSAIDs, including indomethacin, aspirin, and ibuprofen, can all effect healing of a variety of fractures, including those affecting the rat forelimb, vertebra or femur.” – Wheeler and Batt (2011, in the British Journal of Sports Medicine)

Another study, done by Harder and An (2003, in the Journal of Clinical Pharmacology), wrote a concise review of the biological mechanisms by which NSAIDs would inhibit bone healing. If you’re really interested, this is a wonderful article. I highly recommend it to fellow biology and medicine nerds (it’s a little heavy on medical and biochemistry lingo. If the words ‘prostaglandin’, ‘osteoblasts’ and ‘COX-2 inhibitors’ are completely foreign to you, I suggest avoiding the article unless you like headaches and have a Stedman’s sitting by). Their general conclusion:

“Although beneficial effects of NSAIDs are far reaching, like all other medications, unwanted side effects exist. Among these, an inhibitory effect on bone healing has been well documented in animal studies and in vitro investigations in particular. By first elucidating the steps involved in the bone-healing process, the mechanism through which NSAIDs serve to inhibit bone healing becomes clearer…. [Prostaglandins] fulfill an important position in the course of bone healing. It is not surprising, therefore, that the decreased production of [prostaglandins] elicited by NSAIDs could potentially impair the bone-healing process… Only with continued investigation can the answers to these questions and many others hope to be elucidated.” – Harder and An (2003)

A study by Radi & Khan (2005, in the journal Inflammation Research) echo this statement [COX-2 inhibitors are prescription anti-inflammatory drugs, like Vioxx and Celebrex]:

“At this time, large-scale, robust clinical study data do not exist, limiting the relevant assessment of experimental data to humans…. [T]his assessment suggests potential involvement of [prostaglandins] in the healing process of [bone, tendon, and ligament] tissues via modulation by non-selective NSAIDs and selective COX-2 inhibitors.” – Radi & Khan (2005)

There are a lot of other animal or in vitro studies out there, but they get super science-y. So if you’re a science fan, check out this one, or this one, or this one, or this one, or this one, or just go to PubMed and go crazy. If you’re not a science super-nerd. Feel free to ignore them.

When it comes to human studies, results are inconsistent, neither proving or disproving the relationship. These suggest that taking an NSAID after a fracture has occurred might lead to an increase in healing time:

“Studies on patients treated after sustaining a variety of traumatic fractures, including Colles-type, tibia, clavicle, non-union of the femoral diaphysis, and acetabular, produced inconsistent results, with one study showing no difference and the remainder showing delayed healing or an increased risk of non-union.” – Wheeler and Batt (2011)

Additionally, the Wheeler and Batt (2011) review of current literature showed conflicting evidence in the risk of fracture for someone already taking NSAIDs. However, these studies are slightly more complicated, due to confounding factors (such as previous bone density, diet, and level of exercise).

So, Laura, enough with the science. What does this all mean for me and my injury!? Well, dear reader, I can’t really tell you that. I’m not a doctor. Your doctor will know the answer to that. Call your doctor. Doctors are happy to help out. Doctors are awesome.

But for now, I’ll tell you what all this science means to me: ibuprofen is not the wonderfully useful and completely harmless (for a generally healthy lass like myself) drug. Since my possible stress fracture in my foot, I now handle my ibuprofen and Tylenol and Aleve differently. By differently, I mean I’m avoiding it as much as possible. Even if I heal one day more quickly because I’m not taking it, that’s one more day I’ll be running.

Again, I just wanted you all to know about this, since as of a few months ago I’d never heard that simple ibuprofen might actually be hurting me.

In conclusion: Ask your doctor about treating your injuries! Not me. But I encourage you to bring this up with your doctor if you think you might have a serious bone (or tendon/ligament) issue.

[I am not a medical doctor and cannot treat your individual injuries. You all got that point, right?]

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2 Responses to Ibuprofen may not be a runner’s friend.

  1. Amanda Dickey says:

    So it seems, then, that these bone and tendon injuries could just be attributed to each individual person solely healing at different rates? It all may be simply due to a combination of lifestyle habits and genetics and not NSAIDS. Which to me, makes all these studies possibly inconclusive about whether or not you can really trust what they say. I would say these test are debateable for definate information…but thanks for sharing anyhow. 🙂

    • laura says:

      Oh definitely debatable. They have reasonably proven that NSAIDs reduce production of prostaglandins, which are required to rebuild collagen (a primary component in bone, ligament, and tendon). But they don’t have a perfect study showing that this translates to a population level outcome.
      The 2011 review only found 12 human studies that test anything like this (this includes the studies that tested if someone on NSAIDs was more likely to get a stress fracture), and you’re not going to prove this with 12 small studies and it’s impossible to prove a negative.

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