The effect of tocilizumab on bone mineral density, serum levels of Dickkopf-1 and bone remodeling markers in patients with rheumatoid arthritis

Briot, Karine; Rouanet, Stéphanie; Schaeverbeke, Thierry; Etchepare, Fabien; Gaudin, Philippe; Perdriger, Aleth; Vray, Muriel; Steinberg, Ghislaine; Roux, Christian

doi:10.1016/j.jbspin.2014.10.015

Cited by 55 publications

(44 citation statements)

References 26 publications

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“…Our study showed a decrease in the levels of DKK-1 at 6 months of treatment, which is consistent with recently published by Briot et al 20 . In this article, patients with active RA treated with tocilizumab experienced a decrease in DKK1 concentrations and a decrease in formation markers.…”

Section: Discussionsupporting

confidence: 94%

Cambios inducidos en DKK1 en pacientes con artritis reumatoide que inician tratamiento con terapia biológica

Palma-Sánchez¹,

Haro-Martínez²,

Muñoz³

et al. 2016

Rev Osteoporos Metab Miner

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Introduction: The aim of this study is to assess the relationship among inflammatory charge, cardiovascular risk and bone metabolism in patients with rheumatoid arthritis initiating biological therapy treatment. Patients and methods: This is a prospective cohort study conducted in patients diagnosed with active rheumatoid arthritis (RA) assessed in the Rheumatology Unit and initiating biological therapy. Patients will be selected consecutively, with preliminary data on 14 patients. We present preliminary data from 14 patients. Results: Reduced Dickkopf-1 (DKK1) concentrations after commencing biological therapy were detected (baseline: 53.12±60.43 pg/ml vs 6 months 13.5±23.2 pg/ml, p=0.307) but without statistical significance. Changes were found in markers for bone remodeling with increased osteocalcin levels and CTX which were not statistically significant either. Conclusions: We observed a nonsignificant decrease in DKK1 serum in patients with active RA treated with biologic therapy. Expanding the scope of study subjects and pending biochemical determinations will allow us, in the near future, to establish more precisely this link and the relationship of DKK1, bone remodeling, biological therapy and cardiovascular disease in RA patients.

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Section: Discussionsupporting

confidence: 94%

Cambios inducidos en DKK1 en pacientes con artritis reumatoide que inician tratamiento con terapia biológica

Palma-Sánchez¹,

Haro-Martínez²,

Muñoz³

et al. 2016

Rev Osteoporos Metab Miner

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“…Regarding the effect of bDMARD therapy on the Wnt signaling in RA, most of the relevant studies were conducted with TNFα inhibitors [32,39] or an IL-6 receptor (IL-6R) inhibitor, tocilizumab [18,19], and they showed a decrease in the serum level of Dkk-1 in RA patients undergoing these bDMARD treatments. A reduction in the serum level of Dkk-1 may result from the inhibition of the TNFα-and IL-6-dependent induction of Dkk-1 by TNFα inhibitors or anti-IL-6 monoclonal antibody.…”

Section: Discussionmentioning

confidence: 99%

“…Wnt signaling is involved in osteoclastogenesis regulation; the canonical Wnt/β-catenin signaling pathway leads to an upregulation of OPG and a down-regulation of RANKL [14,33]. TNF inhibitors [14,44] or IL-6R inhibitor [14,18,19] increased both the expression of OPG and the OPG/RANKL ratio, possibly due to a promotion of Wnt signaling following a decrease in DKK-1. Similarly, abatacept may elevate the serum level of OPG because it promotes Wnt signaling as described above.…”

Section: Discussionmentioning

confidence: 99%

“…Among the underlying mechanisms, important roles are played by the interaction of immune responses mediated by proinflammatory cytokines such as tumor necrosis factor (TNF), interleukin (IL)-6 and IL-17, and bone biomarkers such as receptor activator of nuclear factor kappa-B ligand (RANKL), osteoprotegerin (OPG), dickkopf-1 (Dkk-1), and sclerostin (SOST) [12][13][14][15]. Effects of bDMARDs including TNF inhibitors [16,17] and IL-6 inhibitors [18][19][20] on bone biomarkers in patients with RA have been reported, but the effect of abatacept on bone biomarkers in patients with RA has not been investigated. Here, we measured the serum levels of five bone biomarkers (Dkk-1, SOST, osteocalcin [OC], osteopontin [OPN], and OPG) using a multiplex bead assay (bone panel) in RA patients treated with abatacept.…”

Section: Introductionmentioning

confidence: 99%

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Association between serum bone biomarker levels and ultrasonographic response in abatacept-treated rheumatoid arthritis patients

Kawashiri

Endo

Nishino

et al. 2020

Preprint

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Background To evaluate the effect of treatment on bone biomarkers and explore whether bone biomarkers are associated with therapeutic response in rheumatoid arthritis (RA) patients treated with abatacept. Methods We enrolled 59 RA patients treated with abatacept from a multicenter prospective ultrasound cohort study of patients who received biologic or targeted synthetic disease-modifying antirheumatic drug (DMARD) therapy. We evaluated the patients' clinical disease activity and musculoskeletal ultrasound (MSUS) scores. The serum concentrations of five bone biomarkers were evaluated (dickkopf-1 [Dkk-1], sclerostin [SOST], osteocalcin [OC], osteopontin [OPN], and osteoprotegerin [OPG]) by multiplex bead assays at baseline, 3, and 6 months: the change over 6 months was defined as the Δ value. 'Power Doppler (PD) responder' was defined as a patient whose Δtotal PD score over 6 months was greater than the median change. Results Abatacept significantly improved clinical disease activity as well as the MSUS score over 6 months. Serum OPG was significantly elevated at 6 months after the introduction of abatacept (p = 0.016). The ΔSOST and ΔOPG values were negatively correlated with the Δtotal PD score (rs = − 0.31, p < 0.05 and rs = − 0.34, p < 0.01, respectively). The serum Dkk-1 at baseline was significantly lower in the PD responders (n = 30) compared to the non-PD responders (n = 29) (p = 0.026). A multivariate logistic regression analysis showed that the serum Dkk-1 at baseline (odds ratio 0.50, p = 0.043) was an independent predictor of PD responder status. Conclusion Serum levels of bone biomarkers may be useful for predicting RA patients' ultrasonographic response to abatacept.

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“…This suggests that systemic IL-6 may be important for explaining the lung-bone inflammatory axis. Ant-IL-6 therapies, such as tocilizumab, have been successful in the treatment of rheumatoid arthritis (47,48). IL-6 has also been shown to impact RANKL expression and influence osteoclastogenesis (18).…”

Section: Interleukin 6 Involvement In Osteoclastogenesismentioning

confidence: 99%

The Effect of Inhalant Organic Dust on Bone Health

Carrington

Poole

2018

Curr Allergy Asthma Rep

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An agriculture organic dust extract inhalation animal model has recently linked lung injury-induced inflammation to systemic bone loss. This process is dependent upon lipopolysaccharide and the toll-like receptor 4 (TLR4) signaling pathway. Downstream systemic interleukin-6 is a key mediator that subsequently activates osteoclastogenesis. Age is a host factor that impacted bone disease with younger mice demonstrating increased susceptibility to bone loss following inhalant exposures as compared to older mice. Supplemental dietary vitamin D was shown to prevent organic dust-induced bone loss, but not lung disease, in animals. Recent animal studies provide new mechanistic insight into the lung-bone inflammatory axis. Host factors, diet, and lipopolysaccharide/TLR4 signaling pathways play a significant role in explaining how inhalant organic dust exposures impact bone health. These investigations might lead to specific targeted therapeutic approaches.

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The effect of tocilizumab on bone mineral density, serum levels of Dickkopf-1 and bone remodeling markers in patients with rheumatoid arthritis

Cited by 55 publications

References 26 publications

Cambios inducidos en DKK1 en pacientes con artritis reumatoide que inician tratamiento con terapia biológica

Cambios inducidos en DKK1 en pacientes con artritis reumatoide que inician tratamiento con terapia biológica

Association between serum bone biomarker levels and ultrasonographic response in abatacept-treated rheumatoid arthritis patients

The Effect of Inhalant Organic Dust on Bone Health

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