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Tumor necrosis factor alpha-mediated joint destruction is inhibited by targeting osteoclasts with osteoprotegerin
Kurt Redlich1, Silvia Hayer, Andrea Maier
1University of Vienna, Vienna, Austria.
Objective:
To study the effects of osteoclast-targeted therapies, such as osteoprotegerin (OPG) and pamidronate, on joint inflammation and bone destruction using a tumor necrosis factor alpha (TNF alpha)-transgenic mouse model.
Methods:
Mice were placed into 5 groups that received either OPG, pamidronate, a combination of both agents, infliximab as a positive control, or phosphate buffered saline as a negative control. Treatment was initiated at the onset of arthritis, continued over 6 weeks, and thereafter, the clinical, radiologic, and histologic outcomes were assessed.
Results:
A significant improvement in clinical symptoms, as assessed by the reduction of paw swelling, was only found in the infliximab group, whereas all other treatment groups failed to show significant improvement. However, when assessing structural damage with radiographic analysis, a significant retardation of joint damage was evident in animals treated with OPG (55% reduction of erosions), pamidronate (50% reduction of erosions) the combination therapy of OPG and pamidronate (64% reduction of erosions), and with infliximab (66% reduction of erosions). Confirming these data, quantitative histologic analysis revealed a significant reduction in the size of bone erosions in all treatment groups (OPG 56%, pamidronate 53%, OPG and pamidronate 81%, and infliximab 46%) compared with the control group. Furthermore, a significant reduction of osteoclast numbers was seen in animals treated with OPG alone or in combination with pamidronate as well as in animals treated with infliximab.
Conclusion:
These data suggest that OPG alone or in combination with bisphosphonates is an effective therapeutic tool for the prevention of TNF alpha-mediated destruction of bone by reducing the number of bone-resorbing cells in the inflammatory tissue.
Insights
Osteoprotegerin (OPG) and pamidronate effectively reduced bone erosion and osteoclast numbers in a mouse model of TNF alpha-mediated arthritis. Clinical symptoms did not significantly improve, but structural joint damage was prevented.
Area of Science:
- Rheumatology
- Immunology
- Pharmacology
Background:
- Tumor necrosis factor alpha (TNF alpha) plays a key role in inflammatory arthritis.
- Osteoclast-targeted therapies aim to mitigate bone destruction in inflammatory joint diseases.
Purpose of the Study:
- To evaluate the efficacy of osteoprotegerin (OPG) and pamidronate in preventing joint inflammation and bone destruction.
- To assess these therapies in a tumor necrosis factor alpha (TNF alpha)-transgenic mouse model of arthritis.
Main Methods:
- Mice with TNF alpha-induced arthritis were treated with OPG, pamidronate, a combination, infliximab (positive control), or saline (negative control) for 6 weeks.
- Clinical, radiographic, and histologic outcomes were assessed to evaluate treatment effects.
Main Results:
- Infliximab improved clinical symptoms (paw swelling), but OPG and pamidronate did not.
- All tested therapies significantly reduced bone erosions and joint damage radiographically and histologically.
- OPG, pamidronate, and infliximab treatments significantly reduced osteoclast numbers in the affected joints.
Conclusions:
- Osteoprotegerin (OPG) alone or combined with bisphosphonates is effective in preventing TNF alpha-mediated bone destruction.
- These therapies work by reducing the number of bone-resorbing osteoclasts in inflammatory tissues.