Arthritis induces early bone high turnover, structural degradation and mechanical weakness.

Antony Nicodemus Antoniou,Bruno Vidal,Maria Fátima Vaz,Inês Cavaleiro,Helena Canhão,Ana Catarina Vale,José Américo Almeida Brito,João Eurico Fonseca,Rita Cascão

doi:10.1371/journal.pone.0117100

Abstract

BackgroundWe have previously found in the chronic SKG mouse model of arthritis that long standing (5 and 8 months) inflammation directly leads to high collagen bone turnover, disorganization of the collagen network, disturbed bone microstructure and degradation of bone biomechanical properties. The main goal of the present work was to study the effects of the first days of the inflammatory process on the microarchitecture and mechanical properties of bone.MethodsTwenty eight Wistar adjuvant-induced arthritis (AIA) rats were monitored during 22 days after disease induction for the inflammatory score, ankle perimeter and body weight. Healthy non-arthritic rats were used as controls for compar-ison. After 22 days of disease progression rats were sacrificed and bone samples were collected for histomorphometrical, energy dispersive X-ray spectroscopical analysis and 3-point bending. Blood samples were also collected for bone turnover markers.ResultsAIA rats had an increased bone turnover (as inferred from increased P1NP and CTX1, p = 0.0010 and p = 0.0002, respectively) and this was paralleled by a decreased mineral content (calcium p = 0.0046 and phos-phorus p = 0.0046). Histomorphometry showed a lower trabecular thickness (p = 0.0002) and bone volume (p = 0.0003) and higher trabecular sepa-ration (p = 0.0009) in the arthritic group as compared with controls. In addition, bone mechanical tests showed evidence of fragility as depicted by diminished values of yield stress and ultimate fracture point (p = 0.0061 and p = 0.0279, re-spectively) in the arthritic group.ConclusionsWe have shown in an AIA rat model that arthritis induc-es early bone high turnover, structural degradation, mineral loss and mechanical weak-ness.

Highlights

Rheumatoid arthritis (RA) is a chronic immune-mediated inflammatory disease, which affects around 1% of the world-population[1]
We have previously found in the chronic SKG mouse model of arthritis that long standing (5 and 8 months) inflammation directly leads to high collagen bone turnover, disorganization of the collagen network, disturbed bone microstructure and degradation of bone biomechanical properties
adjuvant-induced arthritis (AIA) rats had an increased bone turnover and this was paralleled by a decreased mineral content

Summary

Introduction

Rheumatoid arthritis (RA) is a chronic immune-mediated inflammatory disease, which affects around 1% of the world-population[1]. Remodelling of bone is a continuous process by which osteoclasts resorb bone tissue and osteoblasts produce new bone matrix that is subsequently mineralised. Biochemical markers of this bone turnover are produced and released into circulation, providing a read-out of kinetics and the balance between bone loss and formation. Bone-resorbing osteoclasts release carboxy-terminal collagen cross-linking telopeptides (CTX-I), a marker for bone degradation, which is produced by cathepsin K that is involved in systemic bone resorption [3]. During bone formation, collagen is synthesized by osteoblasts in the form of procollagen This precursor contains a short signal sequence and terminal extension peptides: amino-terminal propeptide (PINP) and carboxy-terminal propeptide. The main goal of the present work was to study the effects of the first days of the inflammatory process on the microarchitecture and mechanical properties of bone.

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