Repair of local bone erosions and reversal of systemic bone loss upon therapy with anti-tumor necrosis factor in combination with osteoprotegerin or parathyroid hormone in tumor necrosis factor-mediated arthritis
| Autor: | Kurt Redlich, George Kollias, Helga Bergmeister, Günter Steiner, Paul J. Kostenuik, Silvia Hayer, Nicholas Doerr, Georg Schett, Jochen Zwerina, Josef S. Smolen, Birgit Görtz |
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| Rok vydání: | 2004 |
| Předmět: |
musculoskeletal diseases
medicine.medical_specialty Parathyroid hormone Arthritis Osteoclasts Receptors Cytoplasmic and Nuclear Inflammation Mice Transgenic Bone resorption Bone and Bones Receptors Tumor Necrosis Factor Pathology and Forensic Medicine Bone remodeling Mice Osteoprotegerin Osteoclast Internal medicine medicine Animals Humans Bone Resorption Glycoproteins Osteoblasts business.industry Tumor Necrosis Factor-alpha Osteoblast medicine.disease Arthritis Experimental medicine.anatomical_structure Endocrinology Parathyroid Hormone Drug Therapy Combination medicine.symptom business Regular Articles |
| Zdroj: | The American journal of pathology. 164(2) |
| ISSN: | 0002-9440 |
| Popis: | Local bone erosion and systemic bone loss are hallmarks of rheumatoid arthritis and cause progressive disability. Tumor necrosis factor (TNF) is a key mediator of arthritis and acts catabolically on bone by stimulating bone resorption and inhibiting bone formation. We hypothesized that the concerted action of anti-TNF, which reduces inflammation and parathyroid hormone (PTH), which stimulates bone formation, or osteoprotegerin (OPG), which blocks bone resorption and could lead to repair of local bone erosions and reversal of systemic bone loss. To test this, human TNF-transgenic mice with established erosive arthritis and systemic bone loss were treated with PTH, OPG, and anti-TNF, alone or in combination. Local bone erosions almost fully regressed, on combined treatment with anti-TNF and PTH and/or OPG, suggesting repair of inflammatory skeletal lesions. In contrast, OPG and anti-TNF alone led to arrest of bone erosions but did not achieve repair. Treatment with PTH alone had no influence on the progression of bone erosions. Local bone erosions all showed signs of new bone formation such as the presence of osteoblasts, osteoid formation, and mineralization. Furthermore, systemic bone loss was completely reversed on combined treatment and this effect was mediated by osteoblast stimulation and osteoclast blockade. In summary, we conclude that local joint destruction and systemic inflammatory bone loss because of TNF can regress and that repair requires a combined approach by reducing inflammation, blocking bone resorption, or stimulating bone formation. |
| Databáze: | OpenAIRE |
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