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Cited by 110Bone Metabolism and DiseasesRheumatoid Arthritis Research and TherapiesBone health and treatments

Zoledronic acid protects against local and systemic bone loss in tumor necrosis factor-mediated arthritis.

Herrak, Petra, Görtz, Birgit, Hayer, Silvia, Redlich, Kurt, Reiter, Erika, Gasser, Jürg, Bergmeister, Helga, Kollias, Giorgos +2 more·2004·Arthritis & Rheumatism
DOI 10.1002/art.20384
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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.

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Authors
Herrak, P., Görtz, B., Hayer, S., Redlich, K., Reiter, E., Gasser, J., Bergmeister, H., Kollias, G., Smolen, J. S., & Schett, G.
Affiliations
  • University of Vienna (AT)
  • Novartis (Switzerland) (CH)
  • Alexander Fleming Biomedical Sciences Research Center (GR)
ORCID
Venue
Arthritis & Rheumatism
Publisher
Wiley
Published
2004-07
Volume
50
Issue
7
Pages
2327-2337
ISSN
  • 0004-3591 (ISSN-L)
  • 1529-0131
DOI
10.1002/art.20384
OpenAlex
W2049896159
Cited by
110
References
37
Citations by year
2025: 1 · 2023: 1 · 2021: 3 · 2020: 3 · 2019: 6 · 2018: 2 · 2017: 1 · 2016: 1 · 2015: 6 · 2014: 6 · 2013: 2 · 2012: 5
FWCI
5.44
Type
journal article
Language
en
Open access
closed
Licence
onlinelibrary.wiley.com/termsAndConditions#vor (vor, 5 d)
Locations
  • Arthritis & Rheumatism (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • Center of Molecular Medicine of the Austrian Federal Ministry for Education, Science and Culture
  • City of Vienna
  • Austrian National Bank (8715)
  • Austrian Ministry of Sciences
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bone Metabolism and Diseases
  • Health Sciences › Medicine › Rheumatology › Rheumatoid Arthritis Research and Therapies
  • Health Sciences › Medicine › Oncology › Bone health and treatments
Keywords
zoledronic acid, bisphosphonates, rheumatoid arthritis, TNF-α, bone erosion, osteoclasts, bone loss, calcitonin, anti-TNF therapy, cartilage damage, trabecular bone, bone resorption
MeSH terms
Infliximab, Zoledronic Acid, Animals, Antibodies, Monoclonal, Arthritis, Arthrography, Bone and Bones, Bone Resorption, Calcitonin, Cartilage, Articular, Diphosphonates, Hindlimb, Humans, Imidazoles, Joints, Mice, Transgenic, Osteoclasts, Osteogenesis, Tomography, X-Ray Computed, Tumor Necrosis Factor-alpha, Bone Density, Mice

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