COX-2 INHIBITORS AND FRACTURE HEALING

- by Dr. Robert C. Martin

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Approximately three years ago a new class of drug – Cyclooxygenase 2 inhibitors or Coxibs - was brought to market that replaced the most widely prescribed medications worldwide – NSAIDS – which are often the first choice to manage problems as varied as headaches to menstrual cramps. The use of Cox 2 inhibitor drugs – Celebrex, Bextra, Vioxx - has escalated dramatically since their release with net sales of 6 billion worldwide. Despite their tremendous benefits of Cox 2 inhibitors recent research has shown that these drugs may have side effects just recently discovered.

When Coxibs were developed they seemed to solve a most difficult pharmacological puzzle which was to block only prostaglandins that mediate pain and inflammation leaving other critical prostaglandins alone. Cyclooxygenase is the enzyme that catalyzes or helps facilitate the first two steps in the synthesis of prostaglandins. Prostaglandins, of which there are many types, can be divided into two categories. One category regulates the many “housekeeping” body functions such as the production of the protective lining of the stomach preventing ulcers as well as kidney and liver function. A second category mediates pain, inflammation and temperature. Typically when treating musculoskeletal problems blocking the second type or prostaglandins would be preferred however traditional NSAIDs block the production of all prostaglandins leading to adverse effects for many patients particularly if they take these drugs for many years. These adverse effects can be very serious, such as altered kidney and liver function as well as GI and bleeding problems.

Approximately one third of the money spent on treating arthritis is directed toward the treatment of the adverse effects in the GI tract from traditional NSAIDs.

As a drug that was specifically developed to reduce the risk and incidence of GI ulceration and bleeding, Cox 2 inhibitors have proven to be very effective. As a pain reliever and anti-inflammatory drug Cox 2 inhibitors are widely prescribed in orthopedics for patients with fractures and other muscle, tendon and ligament injuries - Celebrex was even the official anti-inflammatory of the Olympics. Despite their effectiveness in the capacity of pain reliever and anti-inflammatory new research data is suggesting that Cox 2 inhibitors may have some serious unexpected effects on the healing of bone, ligaments, tendons and muscle.

Research done at the University of Medicine and Dentistry New Jersey and published in the Journal of Bone and Mineral Research reported that Cox 2 inhibitors negatively affect the fracture healing process. Whereas for years NSAIDs have been known to marginally slow the rate of fracture healing, ultimately the healed bone achieves optimal strength – equivalent to healing without NSAIDs. In the case of Cox 2 inhibitors fractures not only healed slower but the strength and quality of the bone in the healed areas was not as good. Additionally researchers specifically isolated this effect to the Cox 2 enzyme by studying mice that lack this enzyme.

Another study from UNC Chapel Hill has shown the same effect occurring with tendon and ligament healing.

Does this mean that we should stop taking these medicines, by no means. It does mean that as with all medicines Cox 2 inhibitors have side effects that should be considered and discussed with your doctor when making any treatment decision.