NSAIDs Prevent Proper Fracture Healing

Nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly used to treat pain and inflammation in people with chronic musculoskeletal conditions, such as arthritis. People also commonly take NSAIDs after acute injuries, such as fractures – as can frequently occur in people with osteoporosis – or after joint replacement surgery made necessary by advanced arthritis. However, through an Arthritis Foundation-funded project, scientists have determined that taking NSAIDs after suffering a fracture may inhibit your body’s ability to heal.

What Problem Was Studied?
The process of bone fracture healing can be divided into four phases: immediate, early, regenerative, and remodeling. The immediate phase initiates the healing process. The early phase is characterized by inflammation. The regenerative phase occurs when the fracture is bridged with new bone, and the remodeling phase is when the newly generated bone is replaced with mature bone to restore strength and integrity. The early, inflammatory, phase may be critical to successful fracture healing because the chemical signals released during inflammation may be essential in sustaining the healing cascade.

It is common for people with a fracture to take pain relievers, including COX-2 inhibitors or other NSAIDs, for the first couple of weeks following a fracture. However, treatment with NSAIDs has been shown to delay fracture healing in several animal models. NSAIDs achieve their anti-inflammatory effect by inhibiting cyclooxygenase activity, which inhibits prostaglandin synthesis. To determine what effect COX-2 inhibition has on fracture healing, Arthritis Foundation-funded researcher, J. Patrick O’Connor, PhD, and Ann Marie Simon, BS, at the University of Medicine and Dentistry in Newark, N.J., designed an experiment using rats.

What Was Done in the Study?
One thigh bone of 377 rats was broken and the rats were divided randomly into three study groups: one group to test COX-2 dosage on fracture healing; one group to test length of COX-2 treatment on fracture healing; and one group to test the timing of treatment on fracture healing. After eight weeks, the rats were killed and the state of their fractures was analyzed using X-ray scores and mechanical testing of strength.

What Were the Study Results?
Inhibition of fracture healing was detected with all doses of the COX-2 inhibitor tested. The most significant healing impairment was observed when treatment lasted 15 days or longer. Delaying anti-inflammatory treatment until 14 days after the fracture allowed the fractures to heal properly. COX-2 use before the fracture, but not after the fracture, had no negative effect on healing.

What Does This Mean for People With Arthritis?
The authors were able to deduce that NSAID therapy following a fracture may adversely affect healing in humans. COX-2 activity and prostaglandin levels are essential for normal fracture healing to proceed. Inhibiting the early inflammatory phase of the healing process can ultimately impair fracture healing at later times.

O’Connor concluded, “NSAID use probably should be avoided by patients during fracture healing, especially during the immediate and early inflammatory phases of fracture healing. If a person with arthritis who regularly takes NSAIDs, including COX-2 inhibitors, for their pain and inflammation suffers a fracture or undergoes joint replacement surgery, NSAID therapy probably should be avoided for at least two weeks. Other forms of pain relief, such as acetaminophen or narcotic analgesics, could be given in the interim but this should be done in consultation with a physician.”

Simon AM, O’Connor JP. Dose and time-dependent effects of cyclooxygenase-2 inhibition on fracture-healing. J Bone Joint Surg (Am) 2007;89:500-11.

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