Inflammation and new bone formation: The long lasting debate in axial spondyloarthritis

The complex relation of inflammation to new bone formation in patients with Axial Spondyloarthritis (aSpA) still represents an interesting debate [1]. The two main reasons for this argue focus on having the absence of a good therapeutic efficacy of low or moderate doses of glucocorticoids and Disease Modifying Anti- Rheumatic Drugs (DMARDs) as the first cause; and secondly, the discrepancy in having a dramatic efficacy of Tumor Necrosis Factor (TNF) blockers in active Ankylosing Spondylitis (AS) patients while not being able to prevent new bone formation in the spine. As there is more than inflammation in the relation with new bone formation, other key players are involved in the escalation of both processes and form important links or cofactors in this connection. Across the different subtypes of Spondyloarthritis (SpA), the pathophysiology of axial disease may be quite different from that of the peripheral disease. Genetic risk variants of HLA– B27, interleukin-23 receptor (IL-23R), IL-1A, IL-12B and other factors suggest a partially distinct genetic background. Moreover, whether axial immunopathology is similar between different SpA subtypes or phases of the disease remains mysterious [2]. In a previous study, IL-23 was significantly higher in Inflammatory Bowel Disease (IBD) patients with peripheral arthritis and/or aSpA [3]. The molecular pathways including Bone Morphogenic Proteins (BMPs), Wnt [4, 5], as well as hedgehog proteins that mechanically trigger new bone formation are not yet fully understood. Interestingly, previous bone degradation is not required for the generation of local bone formation [2]. Oxidative stress and lipid peroxidation are accelerated in untreated patients with active AS [6]. Lipid mediators as prostaglandin E 2 may support osteoblast differentiation and fosters new bone formation in SpA due to the proinflammatory effect which is reflected by the high responsiveness to NSAIDs [2]. Cartilage degeneration, indicated by cartilage thinning, enhanced chondrocyte apoptosis, and proteoglycan loss, and subchondral bone thinning, promoted by invasion of the subchondral bone plate by a fibrous tissue originating from the bone marrow, are hallmarks of joint remodeling in AS [7]. These various added factors may provide an indirect explanation for this long lasting question about the relationship between inflammation and new bone formation in aSpA. In view of the argue on the 2 main hypotheses explaining a certain dissociation between inflammation and new bone formation [1], a multistep process has been claimed [8] assuming that all