NDLI: 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.

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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.

Content Provider	Europe PMC
Author	Redlich, Kurt Görtz, Birgit Hayer, Silvia Zwerina, Jochen Doerr, Nicholas Kostenuik, Paul Bergmeister, Helga Kollias, George Steiner, Günter Smolen, Josef S. Schett, Georg
Copyright Year	2004
Abstract	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.
Related Links	https://europepmc.org/backend/ptpmcrender.fcgi?accid=PMC1602264&blobtype=pdf
ISSN	00029440
Volume Number	164
PubMed Central reference number	PMC1602264
Issue Number	2
PubMed reference number	14742260
Journal	Am J Pathol
e-ISSN	15252191
DOI	10.1016/s0002-9440(10)63144-6
Language	English
Publisher	American Society for Investigative Pathology
Publisher Date	2004-02-01
Access Restriction	Open
Rights License	Copyright © American Society for Investigative Pathology
Content Type	Text
Resource Type	Article
Subject	Pathology and Forensic Medicine

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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

Repair of local bone erosions and reversal of systemic bone loss upon therapy with anti-TNF in combination with OPG or PTH in TNF-mediated arthritis

Repair of local bone erosions and reversal of systemic bone loss upon therapy with anti-TNF in combination with OPG or PTH in TNF-mediated arthritis

Repair of local bone erosions by combined treatment with parathyroid hormone, osteoprotegerin and anti-tumor necrosis factor in tumor necrosis factor-transgenic mice

Repair of local bone erosions and reversal of systemic bone loss upon therapy with anti-TNF in combination with OPG or PTH in TNF-mediated arthritis

Repair of local bone erosions by combined treatment with parathyroid hormone, osteoprotegerin and anti-tumor necrosis factor in tumor necrosis factor-transgenic mice

Repair of local bone erosions by combined treatment with parathyroid hormone, osteoprotegerin and anti-tumor necrosis factor in tumor necrosis factor-transgenic mice

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

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

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.

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