Progress in Spondylarthritis. Mechanisms of new bone formation in spondyloarthritis

Department of Musculoskeletal Sciences, Division of Rheumatology, Laboratory for Skeletal Development and Joint Disorders, Katholieke Universiteit Leuven, Belgium.
Arthritis research & therapy (Impact Factor: 3.75). 05/2009; 11(2):221. DOI: 10.1186/ar2642
Source: PubMed


Targeted therapies that neutralize tumour necrosis factor are often able to control the signs and symptoms of spondyloarthritis. However, recent animal model data and clinical observations indicate that control of inflammation may not be sufficient to impede disease progression toward ankylosis in these patients. Bone morphogenetic proteins and WNTs (wingless-type like) are likely to play an important role in ankylosis and could be therapeutic targets. The relationship between inflammation and new bone formation is still unclear. This review summarizes progress made in our understanding of ankylosis and offers an alternative view of the relationship between inflammation and ankylosis.

Download full-text


Available from: Kurt de Vlam
  • Source
    • "At these sites, the new bone is added by a process of endochondral ossification that recapitulates the cellular mechanisms of bone growth that occur during skeletal growth and development in which new bone is formed by replacement of a cartilaginous matrix. Syndesmophytes, which are one of the radiographic hallmarks of the SpAs, represent examples of ossification at the margins of vertebral bodies that are formed via the process of endochondral ossification [10]. Local production of bone growth factors, including TGF-β and BMPs, which play a role in endochonral bone formation during development and post-natally in fracture repair, have been implicated in this process [10–14]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: The seronegative spondyloarthopathies (SpA) share certain common articular and peri-articular features that differ from rheumatoid arthritis (RA) and other forms of inflammatory arthritis. These include the tendency of the SpAs to involve the axial skeleton in addition to the diarthrodial joints, and the prominent involvement of the extra-articular entheses (sites of ligamentous and tendon insertion), which are not common sites of primary pathology in RA and other inflammatory arthropathies. The differential anatomic sites of bone pathology in the SpAs in comparison to the other forms of arthritis suggest that the underlying pathogenic processes and cellular and molecular mechanisms that account for the peri-articular bone pathology involve different underlying disease mechanisms. This review will highlight the molecular and cellular processes that are involved in the pathogenesis of the skeletal pathology in the SpAs, and provide evidence that many of the factors involved in regulation of bone cell function exhibit potent immune-regulatory activity, providing support for the general concept of osteoimmunology.
    Full-text · Article · Jul 2013 · Current Rheumatology Reports
  • Source
    • "Ankylosing spondylitis (AS) is a chronic inflammatory disease characterized by a diverse spectrum of clinical manifestations, including the alteration of joint architecture, joint fusions, and functional impairment in the sacroiliac and spine joint [1], [2]. The exact pathogenesis and the etiology of AS are not fully understood. "
    [Show abstract] [Hide abstract]
    ABSTRACT: The interleukin-23 receptor (IL-23R) has been shown to be associated with ankylosing spondylitis (AS) in many different populations. This study examined whether IL-23R polymorphisms were associated with susceptibility to this disease in a Chinese Han population. Three single-nucleotide polymorphisms (SNP), rs7517847, rs11209032, and rs17375018, were genotyped in 291 AS patients and 312 age-, sex-, and ethnically matched healthy controls using a polymerase chain reaction (PCR) restriction fragment length polymorphism (RFLP) assay. The genotype and allele frequencies of rs17375018, rs7517847, and rs11209032 were not different between the patients with AS and the healthy controls. On the one hand, stratification analysis indicated that the rs17375018 GG genotype and the G allele were increased in AS patients who were HLA-B27 positive (corrected p = 0.024, odds ratio [OR] 2.35, 95% CI 1.30-4.24; p c = 0.006, OR 1.98, 95% CI 1.28-3.07, respectively). On the other hand, the analysis according to clinical characteristics showed a significantly increased prevalence of the homozygous rs17375018 GG genotype and the G allele in patients with AS and uveitis compared with the controls (p c = 0.024 and p c = 0.024, respectively). In addition, haplotype analysis performed with the SHEsis platform revealed no significant difference concerning the haplotypes between AS patients and healthy controls. In this study, the results suggested that the rs17375018 of IL23R was positively associated with HLA-B27-positive AS and that the rs17375018 GG of IL-23R was associated with AS concomitant with uveitis. We found no evidence for an association between the other two SNPs of IL-23R and AS.
    Full-text · Article · Jun 2013 · PLoS ONE
  • Source
    • "Ankylosing spondylitis (AS) is a rheumatic disease characterized by chronic inflammation and new bone formation leading to bone remodeling, primarily in the axial skeleton [1]. Bone remodeling in AS is a dynamic process involving numerous molecules interconnected within the multilevel positive and negative feedback networks [2]. The link between inflammation and bone remodeling has not been fully explained. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Background Clinical activity of ankylosing spondylitis (AS) predicts the natural course of the disease and the response to treatment. Several molecules are involved in new bone formation resulting in structural damage in patients with AS. However, the link between the clinical and molecular phenomena has not yet been fully established. The aim of the study was to investigate the relation between markers of bone remodeling and inflammation with clinical activity and structural damage in AS. Methods We assessed the serum levels of sclerostin, Dickkopf-1 protein, Wingless protein-3a, bone morphogenic protein-7, matrix metalloproteinase-3, osteoprotegerin, bone alkaline phosphatase and inflammatory markers in 50 AS patients with high disease activity (BASDAI ≥ 4), 28 with low disease activity (BASDAI <4), and 23 healthy controls. Cervical and lumbar spine x-rays were performed in 46 patients to measure structural damage (mSASSS). Results Sclerostin level was significantly greater in high disease activity patients than in controls. Wingless protein-3a and Dikkopf-1 protein levels were significantly lower in high activity group compared to low activity group and controls. Negative correlation was found between sclerostin and Dikkopf-1 protein in high activity group (R = −0.28, P = 0.048). The median mSASSS values were not different between patient groups. Conclusions Higher disease activity in AS may not be per se associated with greater new bone formation.
    Full-text · Article · Mar 2013 · BMC Musculoskeletal Disorders
Show more