Osteoporosis: A Paradox in Ankylosing Spondylitis

Abstract

Ankylosing spondylitis is a chronic and severe inflammatory disease of the axial skeleton and the joints. Inflammation is associated with trabecular bone loss leading to osteoporosis but also with corcal new bone formation leading to progressive ankylosis of the spine and sacroiliac joints. This results in an apparent paradox of bone formation and loss taking place at sites closesly located to each other. Osteoporosis can be explained by the impact of inflammation of the bone remodeling cycle. In contrast, new bone formation has been linked to aberrant acvaon of bone morphogenec protein and Wnt signaling. In this commentary, we review recent data on this bone paradox and highlight recent advances including the effect of current drug therapies and the idenfication of new therapeutic targets.

Bone morphogenetic proteins in inflammation, glucose homeostasis and adipose tissue energy metabolism

“…In such rheumatoid conditions bone loss is related to inflammation-associated osteoporosis and new bone formation, as has been often seen in patients with AS. That can be explained by different biological mechanisms steering on the one hand at the bone remodeling cycle and, on the other, to new bone formation originating from the enthesis [47]. These first steps result in a local production of different BMPs by various cell types including inflammatory cells like in peripheral blood mononuclear cells [48] where upregulation of gene expression for BMP2, -4 and -7…”

Juvenile Spondyloarthritis

“…In contrast, new bone formation has been linked to aberrant activation of bone morphogenic protein (BMP) and Wingless-type like (WNT) signaling. (Figure 1 and Figure 2) (Lories, Derese et al 2005;Lories, Luyten et al 2009;Carter and Lories 2011). By contrast, tumor necrosis factor (TNF) does not appear to be the direct trigger for osteophyte formation in AS (Schett and Rudwaleit 2010).…”

Lessons from Genomic Profiling in AS

“…Bone formation and bone loss take place at sites closely located to each other presenting an "apparent paradox", which is reflected in the changes in bone and cartilage metabolism occurring in the AS disease process (Carter & Lories, 2011). Ossification is the hallmark of AS and has been linked to aberrant activation of bone morphogenic protein (BMP) and wingless (WNT) signaling.…”