30 November 2008

NSAIDs, Your Bones, and Surgery

Fractures and Surgery:
Non-steroidal anti-inflammatory drugs are a large class of compounds that inhibit cyclo-oxygenase and thus the formation of prostaglandins, which are involved in bone metabolism. However, the effect of these drugs on bone metabolism is often overlooked. They inhibit osteoblasts at the endosteal bone surface and also reduce both the immune response and the inflammatory response. PGs have been shown to elicit and participate in inflammatory responses, increase osteoclast activity and subsequent bone resorption, and increase osteoblast activity and new bone formation. This apparent integral role for PGs in the process of bone healing, coupled with the knowledge that NSAIDs act by inhibiting the production of PGs, results in an understanding of the likely mechanism through which NSAIDs impart their deleterious effects on bone healing. By inhibiting the COX enzymes and the subsequent production of PGs, NSAIDs not only achieve their desired anti-inflammatory effects but also inhibit the increased production of PGs that is necessary for bone healing to occur.
On studies strong argues, the harmful effects of NSAIDs on bone: 'Despite animal studies which have highlighted the harmful effects of these drugs on the healing of fractures and spinal fusion, they continue to be used commonly for the relief of postoperative pain in the absence of well designed human trials. A random survey of the type of analgesia received by patients undergoing hip arthroplasties on our elective orthopaedic ward showed that 95% (18/19) were being treated with these drugs.' Based on this site ibuprofen has been shown to have an irreversible effect on the healing of fractures. Also the inhibitory effect of these drugs on fracture healing is greater the longer the duration of use.

Hip Surgery:
Another site argues that NSAIDs are good after hip surgery due to prevention of abnormal bone formation. 'Abnormal bone formation in the muscles around the hip occurs after about one third of all hip replacements. Use of an NSAID (apart from low dose aspirin) around the time of surgery reduces the risk of such bone developing by between one half and two thirds with little risk of side effects from treatment. Prevention of abnormal bone formation is likely to reduce the risk of long-term pain, stiffness and disability after hip replacement. However, the effects of treatment on these outcomes needs to be proved in a large-scale trial.'
It seems that NSAIDs have the ability to inhibit bone formation. This could be a good thing after hip surgery or a bad thing after a fracture or spinal fusion. However, more studies are needed.

http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=1113091
http://www.cochrane.org/reviews/en/ab001160.html

6 comments:

KristinaK495 said...

In all your research have you come across any recommendations of drugs to use in place of NSAIDs (in the bad case of fracture or spinal fusion)?

christinew7630 said...

That was a great review of NSAIDS and bone growth. In medical school we often sent patients home with NSAIDS following a fracture or orthopedic surgery. In the 10 years since graduation I have seen a strong trend in not using NSAIDS following frcature or surgery....it seems the orthopedic physicians are paying attention.

LisaB495 said...

The site where I gathered the information recomended that if NSAIDs are used, they should be prescribed in the lowest possible dose for the shortest time, or an agent such as indomethacin might be a better choice, since it has been shown to have a reversible inhibitory effect on bone healing. Indomethacin is a non-steroidal anti-inflammatory drug commonly used to reduce fever, pain, stiffness, and swelling. It works by inhibiting the production of prostaglandins, molecules known to cause these symptoms.

MelissaM7630 said...

This is really interesting given how often NSAIDS are prescribed after surgery. It definitely seems like more studies are warranted in this area to determine when and when not to use NSAIDS after surgery.

Is there any comparable work being done in animals that might lend more insight to humans?

wayala said...

I found this very interesting since NSAIDs are among the most common pain relievers but also the most controversial since NSAIDS prevent the creation of prostaglandins. Going off tangent a bit: about 1% of the general population is allergic to NSAIDS and aspirin. Unfortunately my mom falls in the this small range of people. Since my mom is allergic to NSAIDS and acetaminophens, doctors always have a hard time prescribing her a pain reliever. In most cases Tylenol is considered the drug of choice for her, though she always has to be monitored for the first full dose of the medication. In extreme cases where she cant tolerate Tylenol, she is good to go on morphine.

LisaB495 said...

There is conflicting opinions about giving NSAIDs after surgery and it depends on the type of surgery. On the same topic, orthopaedic surgery, I found the article I first referenced that suggested not giving NSAIDs after a fracture. Another endorced giving NSAIDs after hip surgery to prevent unwanted bone growth. Clearly more research is needed.
As for your question, I found an article that suggests studies in rodents provide no evidence of adverse side effects on bone formation and that human evidence is limited. To read the full piece go to:
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=1114076