TocilizumabV1, Main, Exploration, bibRecord, 003B91

Early effects of IL-6 receptor inhibition on bone homeostasis: a pilot study in women with rheumatoid arthritis

Identifieur interne : 003B91 ( Main/Exploration ); précédent : 003B90; suivant : 003B92

Early effects of IL-6 receptor inhibition on bone homeostasis: a pilot study in women with rheumatoid arthritis

Auteurs : E. Terpos [Grèce] ; K. Fragiadaki [Grèce] ; M. Konsta [Grèce] ; C. Bratengeier [Autriche] ; A. Papatheodorou [Grèce] ; P. P. Sfikakis [Grèce]

Source :

Clinical and experimental rheumatology : (Testo stampato) [ 0392-856X ] ; 2011.

RBID : Pascal:12-0100652

Descripteurs français

Pascal (Inist)
- Polyarthrite rhumatoïde, Tocilizumab, Interleukine 6, Os, Homéostasie, Femme, Ligand RANKL, Rhumatologie, Chronique, Immunomodulateur, Immunodépresseur.
Wicri :
- topic : Femme.

English descriptors

KwdEn :
- Bone, Chronic, Homeostasis, Immunomodulator, Immunosuppressive agent, Interleukin 6, Receptor activator Nfkb ligand, Rheumatoid arthritis, Rheumatology, Tocilizumab, Woman.

Abstract

Objective A critical role of interleukin-6 (IL-6) in bone homeostasis has been suggested in experimental studies. We examined whether inhibition of IL-6 receptor in patients with rheumatoid arthritis (RA) results in early alterations of circulating markers of bone remodelling. Methods Circulating levels of osteoprotegerin, receptor activator of nuclear factor-kappaB ligand (RANKL), Wnt signalling pathway inhibitors Dickkopf-1 (Dkk-1) and sclerostin, markers of bone resorption (C-terminal cross-linking telopeptide of collagen type-I (CTX), tartrate-resistant acid phosphatase isoform-5b) and bone formation (bone-specific alkaline-phosphatase, osteocalcin) were examined in 22 women with active RA before and after two monthly infusions of tocilizumab (8mg/kg each); 'healthy', non-osteopenic, 1:1 age-matched women served as controls. Results At baseline, osteoprotegerin/RANKL ratio in patients was lower than controls by 5-fold; circulating osteoprotegerin correlated negatively with corresponding 28-joint-count disease activity scores and circulating RANKL correlated positively with C-reactive protein. Also, Dkk-1, sclerostin, CTX and osteocalcin levels were higher in RA than controls. After two months, osteoprotegerin/RANKL ratio increased, Dkk-1 decreased and sclerostin increased comparing to baseline; other markers did not change significantly. Increases of osteoprotegerin/RANKL ratio were more prominent in 10 patients who achieved remission or low disease activity after tocilizumab than in 12 patients who did not. In contrast, the significant alterations of both Wnt inhibitors were comparable between these patient subgroups. Conclusions Anti-IL-6 therapy induced suppression of the inflammatory response affects rapidly the disrupted bone homeostasis in active RA. An additional, possibly specific, effect of IL-6 receptor inhibition on bone remodelling in humans should be further examined.

Affiliations:

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Le document en format XML

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<series><title level="j" type="main">Clinical and experimental rheumatology : (Testo stampato)</title>
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<profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Bone</term>
<term>Chronic</term>
<term>Homeostasis</term>
<term>Immunomodulator</term>
<term>Immunosuppressive agent</term>
<term>Interleukin 6</term>
<term>Receptor activator Nfkb ligand</term>
<term>Rheumatoid arthritis</term>
<term>Rheumatology</term>
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<term>Femme</term>
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<term>Chronique</term>
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<front><div type="abstract" xml:lang="en">Objective A critical role of interleukin-6 (IL-6) in bone homeostasis has been suggested in experimental studies. We examined whether inhibition of IL-6 receptor in patients with rheumatoid arthritis (RA) results in early alterations of circulating markers of bone remodelling. Methods Circulating levels of osteoprotegerin, receptor activator of nuclear factor-kappaB ligand (RANKL), Wnt signalling pathway inhibitors Dickkopf-1 (Dkk-1) and sclerostin, markers of bone resorption (C-terminal cross-linking telopeptide of collagen type-I (CTX), tartrate-resistant acid phosphatase isoform-5b) and bone formation (bone-specific alkaline-phosphatase, osteocalcin) were examined in 22 women with active RA before and after two monthly infusions of tocilizumab (8mg/kg each); 'healthy', non-osteopenic, 1:1 age-matched women served as controls. Results At baseline, osteoprotegerin/RANKL ratio in patients was lower than controls by 5-fold; circulating osteoprotegerin correlated negatively with corresponding 28-joint-count disease activity scores and circulating RANKL correlated positively with C-reactive protein. Also, Dkk-1, sclerostin, CTX and osteocalcin levels were higher in RA than controls. After two months, osteoprotegerin/RANKL ratio increased, Dkk-1 decreased and sclerostin increased comparing to baseline; other markers did not change significantly. Increases of osteoprotegerin/RANKL ratio were more prominent in 10 patients who achieved remission or low disease activity after tocilizumab than in 12 patients who did not. In contrast, the significant alterations of both Wnt inhibitors were comparable between these patient subgroups. Conclusions Anti-IL-6 therapy induced suppression of the inflammatory response affects rapidly the disrupted bone homeostasis in active RA. An additional, possibly specific, effect of IL-6 receptor inhibition on bone remodelling in humans should be further examined.</div>
</front>
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<country name="Autriche"><region name="Vienne (Autriche)"><name sortKey="Bratengeier, C" sort="Bratengeier, C" uniqKey="Bratengeier C" first="C." last="Bratengeier">C. Bratengeier</name>
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Early effects of IL-6 receptor inhibition on bone homeostasis: a pilot study in women with rheumatoid arthritis

Early effects of IL-6 receptor inhibition on bone homeostasis: a pilot study in women with rheumatoid arthritis

Source :

Descripteurs français

English descriptors

Abstract

Links toward previous steps (curation, corpus...)

Le document en format XML

Pour manipuler ce document sous Unix (Dilib)

Pour mettre un lien sur cette page dans le réseau Wicri