NSAIDs Side Effects: When You Take NSAIDs is Critical

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We know so little about medicine and the body. That’s quite a statement made in the early 21st century when we believe we know so much. However, there isn’t a month that goes by that doesn’t wreck some sacred procedure or medical belief. This month’s medical “Saay Whaaat” is about new NSAID side effects. Taking them at the wrong time of day can harm your healing.


NSAID stands for Non-Steroidal Anti-inflammatory Drug and includes many of the common medications you see in the grocery store like Motrin, Advil, and Aleve. There are also prescription versions like Celebrex, Voltaren, Cataflam, Dolobid, Lodine, and Indocin. They block inflammation which is how they work to help with pain caused by injuries and chronic pain.

We’ve known about NSAID side effects for years. For example, they can cause stomach ulcers and dramatically increase the risk of heart attacks. So this is a drug class that has issues.

It’s been hotly debated in the orthopedic literature whether these drugs hurt bone healing (1). Most studies say yes and some say no, but despite this information, most orthopedic surgeons and family doctors haven’t gotten the memo. For example, I’ve seen countless patients on NSAIDs while they’re healing from fractures or bone surgeries.

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The Doctor Jeckell and Mr. Hyde NSAID

Your body has a natural rhythm called a circadian clock. We’re learning more about how this works every day, but suffice it to say that does certain things at certain set times and messing with the routine can cause problems. Let’s look at a new category of NSAID side effects which has to do with when you take these drugs.

During the day, our bodies are in tissue breakdown mode. In our bones, the cells that break down the bone are active (called osteoclasts). This is because it’s during the day that our body sustains it’s normal wear and tear trauma. At night is when our bodies repair themselves using our own adult stem cells. It turns out that messing with this critical breakdown and repair is not a good idea.

The researchers in this most recent study wanted to research NSAID side effects to determine if these drugs would impact bone healing depending on when they were given (2). Mice with broken tibias were either given NSAID drugs all day or only in the morning with pain medication (not an anti-inflammatory) at night. The first group suffered from severe impairment of bone healing and a dramatically different gene expression profile. Basically, the NSAID only in the morning was the mild-mannered Dr. Jekyll while using an NSAID at night was the monstrous Mr. Hyde.

Why is this Happening?

NSAIDs block inflammation which is required for healing. That’s why we’ve never allowed any of our stem cell or PRP treated patients on NSAIDs for the first 4-6 weeks after a procedure. Healing happens at night. Hence blocking the normal inflammation needed for healing at night is a big problem that causes this new class of NSAID side effects.

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What Can We Learn About NSAID Dosing and Regenerative Medicine?

If a patient must take NSAIDs to function or needs to restart them earlier after the procedure, the best regimen is to take them is in the morning and not at night. During the evening would be the time to take an analgesic like Tylenol or a mild narcotic substitute like Tramadol.

This also brings up the topic of how good sleep is critical to healing. Hence, working on sleep issues before you try a regenerative medicine procedure like PRP or stem cells is critical. Good sleep=good healing.

The upshot? Hopefully, this new study opens the door to more research about how the timing of certain meds impacts healing. After all, when you switch from giving the patient steroid shots or burning nerves to promoting healing, making sure the body is optimized to heal is critical!



(1) Marquez-Lara A, Hutchinson ID, Nuñez F Jr, Smith TL, Miller AN. Nonsteroidal Anti-Inflammatory Drugs and Bone-Healing: A Systematic Review of Research Quality. JBJS Rev. 2016 Mar 15;4(3). doi: 10.2106/JBJS.RVW.O.00055.

(2) Al-Waeli, H., Nicolau, B., Stone, L. et al. Chronotherapy of Non-Steroidal Anti-Inflammatory Drugs May Enhance Postoperative Recovery. Sci Rep 10, 468 (2020). https://doi.org/10.1038/s41598-019-57215-y

Chris Centeno, MD is a specialist in regenerative medicine and the new field of Interventional Orthopedics. Centeno pioneered orthopedic stem cell procedures in 2005 and is responsible for a large amount of the published research on stem cell use for orthopedic applications. View Profile

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