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Prevention of bone mineral density loss in patients with rheumatoid arthritis treated with anti-TNFalpha therapy.

Marotte H, Miossec P - Biologics (2008)

Bottom Line: In vitro, TNFa reduces osteoblast activity and increases osteoclast activity through RANKL-RANK pathway.Thus, anti-TNFalpha prevents the BMD loss in RA patients.Future studies are needed to address if TNFa blockers have an effect on bone fractures.

View Article: PubMed Central - PubMed

Affiliation: Clinical Immunology Unit, Departments of Immunology and Rheumatology, University of Lyon, and Unité Mixte Hospices Civils de Lyon-bioMérieux, Hôpital Edouard Hérriot, Lyon, France.

ABSTRACT
This review focuses on recent advances in the effect of anti-TNFalpha therapy on bone metabolism and bone mineral density (BMD) in rheumatoid arthritis (RA). RA is a chronic disease characterized by inflammation of the synovial joint, cartilage degradation, and subsequent bone destruction. Bone damage is often manifested as erosions, localized juxta-articular bone loss, or generalized bone loss. Thus, blockade of TNFa not only serves to block inflammation, but also halts the erosive nature of RA and generalized/localized juxta-articular bone loss. Here, we review recent findings showing that anti-TNFa therapy is also effective on halting systemic bone loss. In vitro, TNFa reduces osteoblast activity and increases osteoclast activity through RANKL-RANK pathway. In arthritis animal models, an imbalance between bone formation and resorption is observed. In humans, this coupling of destruction is restored by anti-TNFalpha therapy early on, but only for a few months. Thus, anti-TNFalpha prevents the BMD loss in RA patients. In summary, TNFa blockade is not only able to prevent joint destruction, but it is also able to prevent bone loss in RA patients. Future studies are needed to address if TNFa blockers have an effect on bone fractures.

No MeSH data available.


Related in: MedlinePlus

Increasing the balance of receptor activator of nuclear factor κB ligand (RANKL)-receptor activator of nuclear factor κB (RANK) induced by tumor necrosis factor alpha (TNFα).Abbreviations: OPG, osteoprotegerin; +, stimulation; −, inhibition.
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f1-btt-2-663: Increasing the balance of receptor activator of nuclear factor κB ligand (RANKL)-receptor activator of nuclear factor κB (RANK) induced by tumor necrosis factor alpha (TNFα).Abbreviations: OPG, osteoprotegerin; +, stimulation; −, inhibition.

Mentions: For almost a decade, anti-TNFα therapy has established a new standard in RA therapy, creating new objectives for disease remission on both the clinical and radiological level. Currently, three anti-TNFα drugs are commercially available and have been successfully used in halting both joint inflammation and destruction in RA patients (Charles et al 1999; Maini et al 1999; Weinblatt et al 1999; Genovese et al 2002; Lipsky et al 2000; Keystone et al 2004; Smolen et al 2005). Furthermore TNFα plays a central role not only in RA, but also in common osteoporosis. In fact, TNFα has been shown to increase bone resorption in systemic osteoporosis related to oestrogen deficiency (Pacifici and Avioli 1993). In addition, transgenic mice expressing soluble TNFα receptor to neutralize TNFα, were protected from oestrogen deficiency-related bone loss (Ammann et al 1997). Thus, blockade of TNFα not only serves to block inflammation, but also halts the erosive nature of RA and generalized/localized juxta-articular bone loss. Here, we review recent findings showing that anti-TNFα therapy is also effective on halting systemic bone loss.


Prevention of bone mineral density loss in patients with rheumatoid arthritis treated with anti-TNFalpha therapy.

Marotte H, Miossec P - Biologics (2008)

Increasing the balance of receptor activator of nuclear factor κB ligand (RANKL)-receptor activator of nuclear factor κB (RANK) induced by tumor necrosis factor alpha (TNFα).Abbreviations: OPG, osteoprotegerin; +, stimulation; −, inhibition.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2727908&req=5

f1-btt-2-663: Increasing the balance of receptor activator of nuclear factor κB ligand (RANKL)-receptor activator of nuclear factor κB (RANK) induced by tumor necrosis factor alpha (TNFα).Abbreviations: OPG, osteoprotegerin; +, stimulation; −, inhibition.
Mentions: For almost a decade, anti-TNFα therapy has established a new standard in RA therapy, creating new objectives for disease remission on both the clinical and radiological level. Currently, three anti-TNFα drugs are commercially available and have been successfully used in halting both joint inflammation and destruction in RA patients (Charles et al 1999; Maini et al 1999; Weinblatt et al 1999; Genovese et al 2002; Lipsky et al 2000; Keystone et al 2004; Smolen et al 2005). Furthermore TNFα plays a central role not only in RA, but also in common osteoporosis. In fact, TNFα has been shown to increase bone resorption in systemic osteoporosis related to oestrogen deficiency (Pacifici and Avioli 1993). In addition, transgenic mice expressing soluble TNFα receptor to neutralize TNFα, were protected from oestrogen deficiency-related bone loss (Ammann et al 1997). Thus, blockade of TNFα not only serves to block inflammation, but also halts the erosive nature of RA and generalized/localized juxta-articular bone loss. Here, we review recent findings showing that anti-TNFα therapy is also effective on halting systemic bone loss.

Bottom Line: In vitro, TNFa reduces osteoblast activity and increases osteoclast activity through RANKL-RANK pathway.Thus, anti-TNFalpha prevents the BMD loss in RA patients.Future studies are needed to address if TNFa blockers have an effect on bone fractures.

View Article: PubMed Central - PubMed

Affiliation: Clinical Immunology Unit, Departments of Immunology and Rheumatology, University of Lyon, and Unité Mixte Hospices Civils de Lyon-bioMérieux, Hôpital Edouard Hérriot, Lyon, France.

ABSTRACT
This review focuses on recent advances in the effect of anti-TNFalpha therapy on bone metabolism and bone mineral density (BMD) in rheumatoid arthritis (RA). RA is a chronic disease characterized by inflammation of the synovial joint, cartilage degradation, and subsequent bone destruction. Bone damage is often manifested as erosions, localized juxta-articular bone loss, or generalized bone loss. Thus, blockade of TNFa not only serves to block inflammation, but also halts the erosive nature of RA and generalized/localized juxta-articular bone loss. Here, we review recent findings showing that anti-TNFa therapy is also effective on halting systemic bone loss. In vitro, TNFa reduces osteoblast activity and increases osteoclast activity through RANKL-RANK pathway. In arthritis animal models, an imbalance between bone formation and resorption is observed. In humans, this coupling of destruction is restored by anti-TNFalpha therapy early on, but only for a few months. Thus, anti-TNFalpha prevents the BMD loss in RA patients. In summary, TNFa blockade is not only able to prevent joint destruction, but it is also able to prevent bone loss in RA patients. Future studies are needed to address if TNFa blockers have an effect on bone fractures.

No MeSH data available.


Related in: MedlinePlus