Radiographic progression is associated with resolution of systemic inflammation in patients with axial spondylarthritis treated with tumor necrosis factor α inhibitors: A study of radiographic progression, inflammation on magnetic resonance imaging, and c

Pedersen, Susanne Juhl; Sørensen, Inge Juul; Lambert, Robert G.; Hermann, Kay-Geert A.; Garnero, Patrick; Johansen, Julia S.; Madsen, Ole Rintek; Hansen, Annette; Hansen, Michael Sejer; Thamsborg, Gorm; Andersen, Lis Smedegaard; Majgaard, Ole; Loft, Anne Gitte; Erlendsson, Jon; Asmussen, Karsten; Jurik, Anne Grethe; Møller, Jakob M.; Hasselquist, Maria; Mikkelsen, Dorrit; Østergaard, Mikkel

doi:10.1002/art.30627

Cited by 85 publications

(67 citation statements)

References 42 publications

(46 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Interestingly, we have recently observed that in an organ culture model of mouse enthesis, TNFa inhibits tissue non-specific alkaline phosphatase (TNAP) activity and mineralization [6], indicating that TNF-a actually inhibits ossification in entheses as it does during developmental ossification. Recent MRI studies have shown that resolution of inflammation after anti-TNF treatment is associated with increased syndesmophyte formation, supporting the notion that TNF-a stimulates ossification early and indirectly, while later, it is inhibitory [7]. Strikingly, TNF-a seems to play the same kind of dual role during fracture healing.…”

Section: Introductionmentioning

confidence: 78%

Autocrine stimulation of osteoblast activity by Wnt5a in response to TNF-α in human mesenchymal stem cells

Briolay

Lencel²,

Bessueille

et al. 2013

Biochemical and Biophysical Research Communications

View full text Add to dashboard Cite

a b s t r a c tAlthough anti-tumor necrosis factor (TNF)-a treatments efficiently block inflammation in ankylosing spondylitis (AS), they are inefficient to prevent excessive bone formation. In AS, ossification seems more prone to develop in sites where inflammation has resolved following anti-TNF therapy, suggesting that TNF-a indirectly stimulates ossification. In this context, our objectives were to determine and compare the involvement of Wnt proteins, which are potent growth factors of bone formation, in the effects of TNF-a on osteoblast function. In human mesenchymal stem cells (MSCs), TNF-a significantly increased the levels of Wnt10b and Wnt5a. Associated with this effect, TNF-a stimulated tissue-non specific alkaline phosphatase (TNAP) and mineralization. This effect was mimicked by activation of the canonical bcatenin pathway with either anti-Dkk1 antibodies, lithium chloride (LiCl) or SB216763. TNF-a reduced, and activation of b-catenin had little effect on expression of osteocalcin, a late marker of osteoblast differentiation. Surprisingly, TNF-a failed to stabilize b-catenin and Dkk1 did not inhibit TNF-a effects. In fact, Dkk1 expression was also enhanced in response to TNF-a, perhaps explaining why canonical signaling by Wnt10b was not activated by TNF-a. However, we found that Wnt5a also stimulated TNAP in MSCs cultured in osteogenic conditions, and increased the levels of inflammatory markers such as COX-2. Interestingly, treatment with anti-Wnt5a antibodies reduced endogenous TNAP expression and activity. Collectively, these data suggest that increased levels of Dkk1 may blunt the autocrine effects of Wnt10b, but not that of Wnt5a, acting through non-canonical signaling. Thus, Wnt5a may be potentially involved in the effects of inflammation on bone formation.

show abstract

Section: Introductionmentioning

confidence: 78%

Autocrine stimulation of osteoblast activity by Wnt5a in response to TNF-α in human mesenchymal stem cells

Briolay

Lencel²,

Bessueille

et al. 2013

Biochemical and Biophysical Research Communications

View full text Add to dashboard Cite

show abstract

“…Lumbar spine BMD may be falsely elevated due to the presence of syndesmophytes, especially in patients with advanced AS. In addition, TNFi use can increase syndesmophytes in the short term (31). However, patients receiving TNFi also had BMD increases in the hip, which is unaffected by syndesmophytes.…”

mentioning

confidence: 98%

Meta‐Analysis of Tumor Necrosis Factor Inhibitors and Glucocorticoids on Bone Density in Rheumatoid Arthritis and Ankylosing Spondylitis Trials

Siu

Haraoui

Bissonnette

et al. 2015

Arthritis Care & Research

View full text Add to dashboard Cite

Objective. To examine the impact of antirheumatic drugs on bone mineral density (BMD) in rheumatoid arthritis (RA), ankylosing spondylitis (AS), psoriatic arthritis (PsA), and psoriasis using a systematic review. Methods. Electronic databases were systematically searched for randomized controlled trials. Studies were grouped based on disease, treatment, and site of BMD measurement. Change in BMD (DBMD) from baseline to end of study was recorded. Standardized mean difference (SMD) of DBMD between treatment and controls was standardized for meta-analyses and 95% confidence intervals (95% CIs) were calculated. Results. Treatment effects on BMD were not the primary outcomes of the trials. Thirteen studies were eligible (11 RA, 2 AS, 0 PsA, and 0 psoriasis). For RA, significantly less hand bone loss was seen with tumor necrosis factor inhibitors (TNFi; SMD DBMD 0.33 [95% CI 0.13, 0.53], P 5 0.001, I 2 5 0%) and glucocorticoids (SMD DBMD 0.51 [95% CI 0.20, 0.81], P 5 0.001, I 2 5 0%). TNFi had no significant effect on lumbar spine and hip BMD. Glucocorticoids were associated with a negative effect on lumbar spine (SMD DBMD 20.30 [95% CI 20.55,20.04], P 5 0.02, I 2 5 52%), but not hip BMD. For AS, a significant increase in BMD was seen with TNFi at the lumbar spine (SMD DBMD 0.96 [95% CI 0.64, 1.27], P < 0.001, I 2 5 16%) and hip (SMD DBMD 0.38 [95% CI 0.13, 0.62], P 5 0.003, I 2 5 0%). Data were insufficient to perform meta-analyses in PsA and psoriasis or for other antirheumatic drugs. Conclusion. In RA, TNFi and glucocorticoids appeared to attenuate hand bone loss. TNFi did not impact lumbar spine and hip BMD and glucocorticoids had negative effects on lumbar spine and no effect on hip BMD. In AS, TNFi was associated with improved lumbar spine and hip BMD.

show abstract

“…The presence of erosion may not tell us much about disease activity, but as we already know that the presence of a syndesmophyte is a predictor of damage progression 16 , and if erosion predicts syndesmophytosis, then spinal erosion could turn out to be an earlier predictor of the same outcome. It has been shown that resolution of inflammation with anti-TNF therapy may be associated with development of new syndesmophytes 17,18,19,20 , and so it may be reasonably expected that an accelerated osteoproliferative phase would include the disappearance of erosion, as suggested in this article. Whether this progresses to ankylosis remains to be seen.…”

Section: Rheumatologymentioning

confidence: 85%

Magnetic Resonance Imaging of Vertebral Erosion in Spondyloarthritis

Lambert

2013

J Rheumatol

View full text Add to dashboard Cite

Radiographic progression is associated with resolution of systemic inflammation in patients with axial spondylarthritis treated with tumor necrosis factor α inhibitors: A study of radiographic progression, inflammation on magnetic resonance imaging, and c

Cited by 85 publications

References 42 publications

Autocrine stimulation of osteoblast activity by Wnt5a in response to TNF-α in human mesenchymal stem cells

Autocrine stimulation of osteoblast activity by Wnt5a in response to TNF-α in human mesenchymal stem cells

Meta‐Analysis of Tumor Necrosis Factor Inhibitors and Glucocorticoids on Bone Density in Rheumatoid Arthritis and Ankylosing Spondylitis Trials

Magnetic Resonance Imaging of Vertebral Erosion in Spondyloarthritis

Contact Info

Product

Resources

About