Abstract
Bone morphogenetic proteins (BMPs) are members of the transforming growth factor-beta superfamily and were originally identified as proteins that induce a full cascade of endochondral bone formation in vivo and ectopically. We hypothesized that the BMP signaling pathway could also play a role in the process of ankylosis that characterizes ankylosing spondylitis and related spondyloarthritides. By over expression of noggin, a BMP antagonist, in a dedicated mouse model of joint ankylosis, we provided evidence for this hypothesis. Our current studies focus on the relationship between stromal cell activation and inflammation, a link that is essential in ankylosing spondylitis. Emerging functional and genetic evidence further corroborates the essential role of BMPs in these processes. BMPs can trigger different downstream signaling cascades, in particular Smad and p38 signaling. Inhibition of p38 signaling in vivo in the spontaneous ankylosing enthesitis model appears to accelerate ankylosis while inhibiting in vitro chondrogenesis. Genetic analysis of intercrosses between the susceptible DBA/1 strain and the H2 identical Balb/c strain point towards a region containing the BMP type Ib receptor as a factor determining genetic susceptibility. Recent clinical data suggest that levels of BMPs are higher in patients with progressive ankylosis in comparison with patients that show no structural progression of disease. Taken together, these data support our hypothesis that BMP signaling is a therapeutic target in ankylosing spondylitis.
Highlights
The “Bone Involvement in Arthritis” International Meeting was first held in Venice, in 2004, with the objective of bringing together distinguished international experts in the fields of bone metabolism and rheumatic diseases to discuss emerging knowledge regarding the interplay between rheumatic diseases and the bone tissue
Given the dramatic implications of these rare adverse events (AEs), a drug-free holiday should be considered in patients treated for more than 5 years with BPs, after an accurate evaluation of risks and benefits
Denosumab have been shown to produce a sustained increase of bone mineral density over 8 years of treatment, and to reduce the risk of new fragility fracture up to 5 years of continuous treatment
Summary
The “Bone Involvement in Arthritis” International Meeting was first held in Venice, in 2004, with the objective of bringing together distinguished international experts in the fields of bone metabolism and rheumatic diseases to discuss emerging knowledge regarding the interplay between rheumatic diseases and the bone tissue. Several pharmacological agents [bisphosphonates (BPs), SERMs, teriparatide, PTH 1-84, strontium ranelate, denosumab] have been approved worldwide for the prevention of fragility fractures in patients at risk. Some concerns have been raised about long-term safety of BPs, due to “unexpected” rare adverse events (AEs) potentially associated with their use (atypical fractures, ONJ and esophageal cancer).
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
