Zoledronic acid may protect against local & systemic bone loss in patients with arthritis

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Zoledronic acid protects against local and systemic bone loss in tumor

necrosis factor-mediated arthritis

http://www3.interscience.wiley.com/cgi-bin/abstract/109086366/ABSTRACT

Abstract

Objective

Increased osteoclast activity is a key factor in bone loss in rheumatoid

arthritis (RA). This suggests that osteoclast-targeted therapies could

effectively prevent skeletal damage in patients with RA. Zoledronic acid

(ZA) is one of the most potent agents for blocking osteoclast function.

We therefore investigated whether ZA can inhibit the bone loss

associated with chronic inflammatory conditions.

Methods

Human tumor necrosis factor (TNF)-transgenic (hTNFtg) mice, which

develop severe destructive arthritis as well as osteoporosis, were

treated with phosphate buffered saline, single or repeated doses of ZA,

calcitonin, or anti-TNF, at the onset of arthritis.

Results

Synovial inflammation was not affected by ZA. In contrast, bone erosion

was retarded by a single dose of ZA (-60%) and was almost completely

blocked by repeated administration of ZA (-95%). Cartilage damage was

partly inhibited, and synovial osteoclast counts were significantly

reduced with ZA treatment. Systemic bone mass dramatically increased in

hTNFtg mice after administration of ZA, which was attributable to an

increase in trabecular number and connectivity. In addition, bone

resorption parameters were significantly lowered after administration of

ZA. Calcitonin had no effect on synovial inflammation, bone erosion,

cartilage damage, or systemic bone mass. Anti-TNF entirely blocked

synovial inflammation, bone erosion, synovial osteoclast formation, and

cartilage damage but had only minor effects on systemic bone mass.

Conclusion

ZA appears to be an effective tool for protecting bone from arthritic

damage. In addition to their role in antiinflammatory drug therapy,

modern bisphosphonates are promising candidates for maintaining joint

integrity and reversing systemic bone loss in patients with arthritis.

Petra Herrak 1, Birgit Görtz 1, Silvia Hayer 1, Kurt Redlich 1,

Reiter 1, Jürg Gasser 2, Helga Bergmeister 3, Giorgos Kollias 4, f

S. Smolen 1, Georg Schett 1 *

1University of Vienna, Vienna, Austria

2Novartis, Basel, Switzerland

3Institute of Biological Sciences, University of Vienna, Vienna, Austria

4Institute of Immunology, Fleming Biomedical Sciences Research

Center, Vari, Greece

email: Georg Schett (georg.schett@...)

*Correspondence to Georg Schett, Department of Internal Medicine III,

Division of Rheumatology, University of Vienna, Währinger Gürtel 18-20,

A-1090 Vienna, Austria

Drs. Herrak and Görtz contributed equally to this work.

Funded by:

Center of Molecular Medicine of the Austrian Federal Ministry for

Education, Science and Culture

City of Vienna

Austrian National Bank; Grant Number: 8715

Austrian Ministry of Sciences