- Meeting abstract
Zoledronic acid protects from local and systemic bone loss in TNF-mediated arthritis
Arthritis Res Ther volume 6, Article number: 85 (2004)
Increased osteoclast activity is a key factor for bone loss in rheumatoid arthritis (RA). This suggests that osteoclast-targeted therapies could effectively prevent skeletal damage in RA. Zoledronic acid (ZA) is one of the most potent agents to block osteoclast function. We therefore investigated whether ZA can inhibit inflammatory bone loss.
Human 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.
Synovial inflammation was not affected by ZA. In contrast, bone erosion was retarded by single administration (-60%) and almost completely blocked by repeated administration (-95%) of ZA. Cartilage damage was partly inhibited (-40%), and synovial osteoclast counts were significantly reduced upon ZA treatment. Systemic bone mass dramatically increased in hTNFtg mice upon ZA administration, which was due to an increase of trabecular number and connectivity. In addition, bone resorption parameters were significantly lowered after ZA. Calcitonin had no effect on synovial inflammation, bone erosions, 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.
ZA appears an effective tool with which to protect bone from arthritic damage. In addition to anti-inflammatory drug therapy, modern bisphosphonates are promising candidates to maintain joint integrity and to reverse systemic bone loss in arthritis.
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Zwerina, J., Herrak, P., Goertz, B. et al. Zoledronic acid protects from local and systemic bone loss in TNF-mediated arthritis. Arthritis Res Ther 6 (Suppl 1), 85 (2004). https://doi.org/10.1186/ar1127
- Zoledronic Acid
- Bone Erosion
- Cartilage Damage
- Synovial Inflammation