Bone Protective Effect of Simvastatin in Experimental Arthritis
JANET L. FUNK, JIANLIANG CHEN, KATHERINE J. DOWNEY, and R. ANDREW CLARK
Methods. Hydrolyzed simvastatin (20 mg/kg/day) was administered subcutaneously to female Lewis rats 4 days before or 8 days after induction of arthritis by intraperitoneal injection of streptococcal cell wall or vehicle. Effects of simvastatin (vs vehicle) on periarticular bone, assessed by bone mineral density (BMD), biochemical markers of bone turnover, and joint histology, were determined. Effects on joint swelling were assessed clinically and histologically.
Results. Simvastatin prevented early and late joint inflammation in association with a decrease in articular macrophage influx. Simvastatin suppressed the periarticular bone destruction occurring late in the course of disease, preserving periarticular BMD and preventing increases in periarticular osteoclasts and serum pyridinoline levels in arthritic animals, while having no effect on these measures in normal animals. Osteocalcin levels, which were decreased in arthritic animals, were unaltered by statin treatment.
Conclusion. Our results suggest that inhibition of HMG-CoA reductase may be therapeutically useful in preserving periarticular bone in RA joints via suppression of inflammation-induced bone resorption. (First Release May 1 2008; J Rheumatol 2008;35:1083-91)
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From the Department of Medicine, University of Arizona, Tucson, Arizona, USA.
Supported by a Medical School Research Grant from Merck and Company, Inc.
J.L. Funk, MD; J. Chen, MD; K.J. Downey, MS; R.A. Clark, MD.
Address reprint requests to Dr. J. Funk, Department of Medicine, University of Arizona, AHSC, Box 24-5218, Tucson, AZ 85724. E-mail: firstname.lastname@example.org
Accepted for publication January 29, 2008.