Home

Current Issue

Archives

Guidelines for Authors & Reviewers

Classified Ads

Links

Search PubMed

Subscriptions

Subscriber Registration

Guidelines for Website Users

JRheum Update Service

Contact Info

JANET L. FUNK, JIANLIANG CHEN, KATHERINE J. DOWNEY, and R. ANDREW CLARK

ABSTRACT.

Objective. Emerging evidence suggests that clinically important antiinflammatory effects of HMG-CoA reductase inhibition may extend beyond cardiovascular disease to other inflammatory disorders, such as rheumatoid arthritis (RA). Protective bone-specific anabolic and antiresorptive effects of HMG-CoA reductase inhibitors have also been evaluated in normal and osteoporotic bone. The specific effect of statins on inflammation-induced bone loss has not previously been a focus of evaluation. We investigated whether simvastatin, a potent HMG-CoA reductase inhibitor, alters bone turnover in an animal model of RA, thus preventing periarticular bone loss.

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. (J Rheumatol First Release May 1 2008)

Key Indexing Terms:

BONE
ARTHRITIS
SIMVASTATIN
HMG-COA REDUCTASE
JOINT

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: jfunk@u.arizona.edu

Accepted for publication January 29, 2008.