Bone protective effect of simvastatin in experimental arthritis

Janet L Funk, Jianliang Chen, Katherine J. Downey, R. Andrew Clark

Research output: Contribution to journalArticle

33 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)1083-1091
Number of pages9
JournalJournal of Rheumatology
Volume35
Issue number6
StatePublished - Jun 2008

Fingerprint

Experimental Arthritis
Simvastatin
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Bone and Bones
Joints
Arthritis
Hydroxymethylglutaryl CoA Reductases
Rheumatoid Arthritis
Bone Remodeling
Bone Density
Inflammation
Anabolic Agents
Osteitis
Osteocalcin
Osteoclasts
Bone Resorption
Intraperitoneal Injections
Cell Wall
Histology
Anti-Inflammatory Agents

Keywords

  • Arthritis
  • Bone
  • HMG-CoA reductase
  • Joint
  • Simvastatin

ASJC Scopus subject areas

  • Rheumatology
  • Immunology

Cite this

Funk, J. L., Chen, J., Downey, K. J., & Clark, R. A. (2008). Bone protective effect of simvastatin in experimental arthritis. Journal of Rheumatology, 35(6), 1083-1091.

Bone protective effect of simvastatin in experimental arthritis. / Funk, Janet L; Chen, Jianliang; Downey, Katherine J.; Clark, R. Andrew.

In: Journal of Rheumatology, Vol. 35, No. 6, 06.2008, p. 1083-1091.

Research output: Contribution to journalArticle

Funk, JL, Chen, J, Downey, KJ & Clark, RA 2008, 'Bone protective effect of simvastatin in experimental arthritis', Journal of Rheumatology, vol. 35, no. 6, pp. 1083-1091.
Funk, Janet L ; Chen, Jianliang ; Downey, Katherine J. ; Clark, R. Andrew. / Bone protective effect of simvastatin in experimental arthritis. In: Journal of Rheumatology. 2008 ; Vol. 35, No. 6. pp. 1083-1091.
@article{2750f77c464d4a849ba7f757512e937f,
title = "Bone protective effect of simvastatin in experimental arthritis",
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.",
keywords = "Arthritis, Bone, HMG-CoA reductase, Joint, Simvastatin",
author = "Funk, {Janet L} and Jianliang Chen and Downey, {Katherine J.} and Clark, {R. Andrew}",
year = "2008",
month = "6",
language = "English (US)",
volume = "35",
pages = "1083--1091",
journal = "Journal of Rheumatology",
issn = "0315-162X",
publisher = "Journal of Rheumatology",
number = "6",

}

TY - JOUR

T1 - Bone protective effect of simvastatin in experimental arthritis

AU - Funk, Janet L

AU - Chen, Jianliang

AU - Downey, Katherine J.

AU - Clark, R. Andrew

PY - 2008/6

Y1 - 2008/6

N2 - 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.

AB - 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.

KW - Arthritis

KW - Bone

KW - HMG-CoA reductase

KW - Joint

KW - Simvastatin

UR - http://www.scopus.com/inward/record.url?scp=44949177577&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=44949177577&partnerID=8YFLogxK

M3 - Article

C2 - 18464303

AN - SCOPUS:44949177577

VL - 35

SP - 1083

EP - 1091

JO - Journal of Rheumatology

JF - Journal of Rheumatology

SN - 0315-162X

IS - 6

ER -