Bone healing optimized: Take your NSAIDs at the right time

Bone healing is a long process that often requires the use of pain meds to manage pain. However, there is evidence that the use of non-steroidal anti-inflammatory drugs(NSAIDs) can impair the healing process.

A new study indicates that it’s not the use of NSAIDs, per se, that impacts bone healing. Instead, it’s the use of NSAIDs at the wrong time that can delay or lead to incomplete healing.

Interestingly, in addition to altering pain sensitivity, NSAIDs appear to also upregulate genes that control the circadian clock. In this blog we’ll cover this study, why timing is so important, and how you can use this information to your advantage.

Bone healing: NSAIDs during the day vs the night

Chronopharmacology is the use of timing to affect the efficacy or side effects of pharmaceutical drugs. It works by timing the use of drugs to coincide with the patient’s circadian rhythm to boost efficacy and decrease side effects.

In this study, they used a mouse model of bone fracture to assess pain sensitivity and healing. There were 3 groups:

  • A control group receiving no NSAIDs
  • An “active” group receiving NSAIDs only during the active period
  • An “inactive” group receiving NSAIDs only during the inactive period

Active vs inactive is an important consideration because mice are nocturnal while we are diurnal.

The study found that mice receiving NSAIDs during their active period had less pain and healed better than the other groups. Gene expression at the injury site was assessed to determine differences between the conditions.

There was a more than 1.5-fold increased expression of the core clock gene PER2 in the active group. Additionally, there was an upregulation in genes related to bone healing in the active group.

All in all, taking NSAIDs during the active period decreased pain and increased bone healing. This was likely due to the synchronization of drug use with the circadian rhythm.

How to get the same bone healing benefits

To get the same benefits from this study, you should take NSAIDs during the day and analgesics during the night. The improved healing in this study is likely due to synchronizing NSAID use with the master circadian clock.

Cortisol is a major output of the master circadian clock. Like NSAIDs, it also inhibits the cyclooxygenase(COX) pathways. These pathways create inflammatory cytokines, so timing inhibition with our naturally produced COX inhibitor boosts healing.

It’s important to point out that getting these same benefits isn’t simply a matter of timing these drugs in the morning. Our environmental exposure to time-setting cues sets our circadian rhythm. In order to build a strong circadian rhythm, you have to pay attention to things such as:

  • Light exposure
  • Feeding/fasting cycle
  • Stress exposure
  • Sleep hygiene
  • Exercise/physical activity

The mice in this study were raised in a circadian lab that controls these variables. So in order for your to get the same benefits, you need to control the same variables. Under ideal conditions, factors that affect bone healing follow this rhythm:

Bone healing circadian gene expression

If you’re not practicing good circadian principles, the map of your healing pathways will be off. In other words, your recovery won’t be optimized.


Timing the use of pharmaceutical drugs leads to enhanced efficacy and decreased side effects. This study found that the use of NSAIDs during the active period of mice enhanced bone healing compared to not taking NSAIDs or taking them during the inactive period.

This effect was mediated, at least in part, to improving the circadian rhythm. In humans, this means taking NSAIDs during the day and avoiding them at night. But to get these benefits, it’s essential to practice good circadian principles.

I’ve discussed the basics of this in a blog you can find here and a video on the Hack Your Gut Facebook page.

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