Repair of Bone Erosion in Rheumatoid Arthritis by Denosumab: A High‐Resolution Peripheral Quantitative Computed Tomography Study

Yue, Jiang; Griffith, James F.; Fan, Xiaoxi; Shi, Lin; Wang, Defeng; Shen, Jiayun; Wong, Priscilla; Li, Edmund K.; Li, Martin; Li, Tena K; Zhu, Tracy Y.; Hung, Vivian Wing Yin; Qin, Ling; Tam, Lai‐Shan

doi:10.1002/acr.23133

Cited by 68 publications

(52 citation statements)

References 40 publications

(59 reference statements)

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“…Monitoring these individual small cortical interruptions might be useful in understanding the pathogenesis of RA and might also be of value for evaluating the progression of structural damage or responsiveness to treatment in individual patients with RA. Previous research demonstrated, for example, repair processes of existing large pathological interruptions with HR‐pQCT in those patients using tumor necrosis factor inhibitors, interleukin‐6, or receptor activator of nuclear factor kappa B ligand (RANKL) blockers …”

Section: Discussionmentioning

confidence: 99%

Assessment of Cortical Interruptions in the Finger Joints of Patients With Rheumatoid Arthritis Using HR-pQCT, Radiography, and MRI

Peters

Tubergen

Scharmga

et al. 2018

Journal of Bone and Mineral Research

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Small cortical interruptions may be the first sign of an erosion, and more interruptions can be found in patients with rheumatoid arthritis (RA) compared with healthy subjects. First, we compared the number and size of interruptions in patients with RA with healthy subjects using high-resolution peripheral quantitative CT (HR-pQCT). Second, we investigated the association between structural damage and inflammatory markers on conventional radiography (CR) and MRI with interruptions on HR-pQCT. Third, the added value of HR-pQCT over CR and MRI was investigated. The finger joints of 39 patients with RA and 38 healthy subjects were examined through CR, MRI, and HR-pQCT. CRs were scored using the Sharp/Van der Heijde method. MRI images were analyzed for the presence of erosions, bone marrow edema, and synovitis. HR-pQCT images were analyzed for the number, surface area, and volume of interruptions using a semiautomated algorithm. Descriptives were calculated and associations were tested using generalized estimating equations. Significantly more interruptions and both a larger surface area and the volume of interruptions were detected in the metacarpophalangeal joints of patients with RA compared with healthy subjects (median, 2.0, 1.42 mm , and 0.48 mm versus 1.0, 0.69 mm , and 0.23 mm , respectively; all p < 0.01). Findings on CR and MRI were significantly associated with more and larger interruptions on HR-pQCT (prevalence ratios [PRs] ranging from 1.03 to 7.74; all p < 0.01) in all subjects, and were consistent in patients with RA alone. Having RA was significantly associated with more and larger interruptions on HR-pQCT (PRs, 2.33 to 5.39; all p < 0.01), also after adjustment for findings on CR or MRI. More and larger cortical interruptions were found in the finger joints of patients with RA versus healthy subjects, also after adjustment for findings on CR or MRI, implying that HR-pQCT imaging may be of value in addition to CR and MRI for the evaluation of structural damage in patients with RA. © 2018 The Authors. Journal of Bone and Mineral Research Published by Wiley Periodicals Inc.

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Section: Discussionmentioning

confidence: 99%

Assessment of Cortical Interruptions in the Finger Joints of Patients With Rheumatoid Arthritis Using HR-pQCT, Radiography, and MRI

Peters

Tubergen

Scharmga

et al. 2018

Journal of Bone and Mineral Research

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“…The details of the methodology have been published before . Briefly, the second metacarpal head (MC2) of the non‐dominant hand were examined by HR‐pQCT (XtremeCT; Scanco Medical AG, Bruttisellen, Switzerland) at baseline and at 12 months.…”

Section: Methodsmentioning

confidence: 99%

“…Briefly, the second metacarpal head (MC2) of the non‐dominant hand were examined by HR‐pQCT (XtremeCT; Scanco Medical AG, Bruttisellen, Switzerland) at baseline and at 12 months. The MC2 is the most frequently affected metacarpal head in RA when assessed by ultrasound or micro‐CT . Therefore, assessment was confined to the MC2 region to optimize time efficiency and minimize motion artefact.…”

Section: Methodsmentioning

confidence: 99%

Circulating miR‐99b‐5p as a novel predictor of erosion progression on high‐resolution peripheral quantitative computed tomography in early rheumatoid arthritis: A prospective cohort study

et al. 2019

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Objectives To compare micro RNA (miRNA) expression: (a) between healthy individuals and early rheumatoid arthritis (ERA) patients with and without erosion on high‐resolution peripheral quantitative computed tomography (HR‐pQCT) at baseline; and (b) to explore whether these miRNAs could inform a signature predictive of erosion progression despite treatment with conventional synthetic disease‐modifying antirheumatic drugs (csDMARDs). Methods The second metacarpophalangeal head (MCP2) was scanned by HR‐pQCT at baseline and 1 year in 117 ERA patients. We performed global profiling of 377 miRNAs in 10 ERA patients with and without erosion on HR‐pQCT at baseline and six healthy controls. Validation of the miRNAs of interest were conducted using TaqMan® quantitative real‐time polymerase chain reaction in the validation ERA cohort (n = 117) at baseline. Correlation between the candidate miRNAs and erosion progression over 1 year were also assessed. Results In the 377 screened miRNAs, 94 (60.6%) miRNAs were upregulated in patients with erosions, with 13 (8.4%) upregulated more than 2‐fold. Sixty‐one (39.4%) miRNAs were downregulated in patients with erosions, with 6 (3.9%) downregulated more than 2‐fold. Expression of miR‐143‐3p, miR‐145‐5p and miR‐99b‐5p were significantly higher in the plasma of ERA patients with erosions compared with those without erosions. Logistic regression analysis revealed that the baseline expression of miR‐99b‐5p was an independent predictor of erosion progression at month 12 (Exp [B] = 4.257, 95% CI 1.178‐15.386, P = 0.027). Conclusions Differential expressions of circulating miR‐143‐3p, miR‐145‐5p and miR‐99b‐5p in the plasma of ERA patients may characterize a severe form of the disease. MiR‐99b‐5p, in particular, may serve as a possible predictor for erosion progression.

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“…Several studies documented a potent effect of DMab on bone erosion and bone mineral density (BMD) in RA (Table 1). In addition, high-resolution quantitative computed tomography studies performed on RA patients revealed partial bone repair (decrease depth, width and volume of erosions) was noted after 6 months of treatment with DMab but not alendronate (110). …”

Section: Dmab In Ramentioning

confidence: 99%

Denosumab: targeting the RANKL pathway to treat rheumatoid arthritis

Chiu

Ritchlin

2016

Expert Opinion on Biological Therapy

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Introduction Rheumatoid arthritis (RA) is a chronic inflammatory disorder characterized by focal pathologic bone resorption due to excessive activity of osteoclasts (OC). Receptor activator of nuclear factor kappa B ligand (RANKL) is essential for the proliferation, differentiation, and survival of OC. Denosumab (DMab) is a humanized monoclonal antibody that binds to RANKL with high affinity and blocks its subsequent association with its receptor RANK on the surface of OC precursors. Area Covered The authors review the molecular and cellular mechanisms underlying therapeutic applications of DMab, provide recent highlights on pharmacology, efficacy and safety of DMab, and discuss the potential of DMab as a novel therapeutic option for the treatment of rheumatoid arthritis. Expert opinion Clinical results suggest that DMab is efficient both in systemic and articular bone loss in RA with limited side effects. Diminished bone erosion activity was also noted in RA patients on corticosteroids and bisphosphonates. Combination of DMab with an anti-TNF agent was not associated with increased infection rates. Collectively, these data indicate that DMab, in combination with methotrexate and possibly other conventional synthetic Disease Modifying Anti-Rheumatic Drugs (csDMARDs), is an effective, safe and cost-effective option for the treatment of RA.

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Repair of Bone Erosion in Rheumatoid Arthritis by Denosumab: A High‐Resolution Peripheral Quantitative Computed Tomography Study

Cited by 68 publications

References 40 publications

Assessment of Cortical Interruptions in the Finger Joints of Patients With Rheumatoid Arthritis Using HR-pQCT, Radiography, and MRI

Assessment of Cortical Interruptions in the Finger Joints of Patients With Rheumatoid Arthritis Using HR-pQCT, Radiography, and MRI

Circulating miR‐99b‐5p as a novel predictor of erosion progression on high‐resolution peripheral quantitative computed tomography in early rheumatoid arthritis: A prospective cohort study

Denosumab: targeting the RANKL pathway to treat rheumatoid arthritis

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