RESEARCH - The decrease of soluble RAGE levels in RA patients following HRT is associated with increased BMD and diminished bone/cartilage turnover

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Rheumatology Advance Access published online on May 4, 2009

Rheumatology, doi:10.1093/rheumatology/kep079

The decrease of soluble RAGE levels in rheumatoid arthritis patients

following hormone replacement therapy is associated with increased

bone mineral density and diminished bone/cartilage turnover: a

randomized controlled trial

Rille Pullerits1,*, Helena Forsblad d'Elia1,*, Andrej Tarkowski1, and

Hans Carlsten1

1Department of Rheumatology and Inflammation Research, University of

Gothenburg, Gothenburg, Sweden

Abstract

Objective. The aim of the study was to prospectively investigate the

effects of HRT on serum soluble receptor for advanced glycation end

product (sRAGE) levels in RA patients and to determine whether sRAGE

production is related to bone/cartilage metabolism.

Methods. Eighty-eight post-menopausal RA patients were randomized to

receive vitamin D3 and calcium supplementation with or without HRT

(oestradiol plus noretisterone acetate). The levels of total sRAGE in

sera were measured before, 1 and 2 years after treatment initiation.

Potential associations between sRAGE levels, bone/cartilage metabolic

markers and BMD were investigated.

Results. Patients receiving HRT displayed significantly decreased

levels of serum sRAGE at 1 and 2 years as compared with levels at

study entry. The increase in serum oestradiol was associated with the

decline in sRAGE levels. Importantly, sRAGE levels at baseline

significantly correlated with bone/cartilage turnover markers

including C-terminal propeptide of type I procollagen, carboxyterminal

telopeptide of type I collagen and cartilage oligomeric matrix

protein, and the decrease of sRAGE levels paralleled with diminished

concentration of these molecules. BMD in hip and femoral neck and

progression of Larsen score at 1 year were associated with baseline

sRAGE levels. The decline in sRAGE levels significantly correlated

with an increase in total BMD following 2 years of treatment in

patients receiving HRT but not in the control group.

Conclusion. Our findings suggest that HRT decreases the levels of

endogenous sRAGE in post-menopausal RA patients implicating its role

in sRAGE regulation. In addition, serum sRAGE was associated with BMD

and markers of bone/cartilage metabolism. These data suggest that

sRAGE is involved directly or indirectly in bone metabolism.

http://rheumatology.oxfordjournals.org/cgi/content/abstract/kep079v1?papetoc

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