RESEARCH - Low cytochrome P450 activity may trigger steroid-induced osteonecrosis

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Low cytochrome P450 activity may trigger steroid-induced osteonecrosis

11/26/2006

By: Reuters Health

NEW YORK (Reuters Health), Nov 26 - Patients with low activity of hepatic

cytochrome P450 (CYP) 3A are at increased risk for corticosteroid-induced

osteonecrosis of the femoral head (ONFH), Japanese researchers report.

ONFH, which typically causes pain and disability at the hip joint, affects

up to 20,000 people in the U.S. annually. Previous reports have shown that

regular corticosteroid use increases the risk of this disease in a

dose-dependent fashion.

Since corticosteroids are primarily metabolized by CYP3A, low activity of

this enzyme complex might increase plasma levels of the steroid, potentially

increasing the risk of ONFH.

Dr. Yasunori, from Osaka City University in Japan, and colleagues

investigated this possibility by measuring CYP3A activity in 26 patients

with steroid-induced ONFH, 29 patients with alcohol-related ONFH, and 75

without ONFH control subjects undergoing orthopedic surgery. Hepatic CYP3A

activity was estimated by measuring the clearance of intravenous midazolam.

The researchers' findings appear in the October issue of Clinical

Pharmacology and Therapeutics.

Hepatic CYP3A activity was significantly lower in patients with

steroid-induced ONFH compared with the other groups (p < 0.001). The

presence of low CYP3A activity raised the risk of steroid-induced ONFH by

9.08-fold.

" It may be possible to reduce the risk of ONFH by adjusting the dose of

corticosteroids to match the capacity of individual patients to metabolize

these drugs, " Dr. Yasunori's team concludes. " To further validate this

method, an additional prospective study to eliminate steroid-induced ONFH is

planned. "

Last Updated: 2006-11-24 15:00:27 -0400 (Reuters Health)

Clin Pharmacol Ther 2006;80:396-402.

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