Assessment of 3-month changes in bone microstructure under anti-TNF\u03b1 therapy in patients with rheumatoid arthritis using high-resolution peripheral quantitative computed tomography (HR-pQCT)

Tomohiro Shimizu,Ursula Heilmeier,Thomas M Link,Nattagan Chanchek,Andrew J Burghardt,Jingshan Gong,Jonathan Graf,John B Imboden,Hyo Jin Choi,Xiaojuan Li,Matthew Tanaka

doi:10.1186/s13075-017-1430-x

Abstract

BackgroundAlthough one study showed minimal progression of erosions in patients with rheumatoid arthritis (RA) one year after TNFα inhibition therapy, no studies have investigated very early bone changes after initiation of anti-TNFα treatment. We investigated the effects of 3-month anti-TNFα treatment on bone erosion progression and bone microarchitecture in RA patients using high-resolution peripheral quantitative computed tomography (HR-pQCT).MethodsPatients with RA (n = 27) (17 in the anti-TNFα and 10 in the MTX-only group) underwent assessment of disease activity score in 28 joints (DAS-28), radiographs, 3-T magnetic resonance imaging (MRI) and HR-pQCT of metacarpophalangeal and wrist joints at baseline and 3 months. HR-pQCT-derived erosion volume, joint volume/width and bone microarchitecture were computed and joint destruction was assessed using Sharp and RAMRIS scorings on radiographs and MRI, respectively.ResultsOverall, 73 erosions were identified by HR-pQCT at baseline. Over 3 months, the anti-TNFα group had decreased mean erosion volume; increased erosion volume was observed in one clinical non-responder. The MTX-only group in contrast, trended toward increasing erosion volume despite low disease activity. In the anti-TNFα group, joint-space width and volume of MCP joints decreased significantly and was positively correlated with erosion volume changes (R2 = 0.311, p = 0.013; R2 = 0.527, p = 0.003, respectively). In addition, erosion volume changes were significantly negatively correlated with changes in trabecular bone mineral density (R2 = 0.353, p = 0.020) in this group. We observed significant correlation between percentage change in erosion volume and change in DAS-28 erythrocyte sedimentation rate and C-reactive protein CRP scores (R2 = 0.558, p < 0.001; R2 = 0.745, p < 0.001, respectively) in all patients.ConclusionsUsing HR-pQCT, our data suggest that anti-TNFα treatment prevents erosion progression and deterioration of bone microarchitecture within the first 3 months of treatment, one patient not responding to treatment, had significant progression of bone erosions within this short time period. Patients with low disease activity scores (<3.2) can have continuous HR-pQCT-detectable progression of erosive disease with MTX treatment only. HR-pQCT can be a sensitive, powerful tool to quantify bone changes and monitor RA treatment short term (such as 3 months).

Highlights

One study showed minimal progression of erosions in patients with rheumatoid arthritis (RA) one year after Tumor necrosis factor alpha (TNFα) inhibition therapy, no studies have investigated very early bone changes after initiation of anti-TNFα treatment
Using high-resolution peripheral quantitative computed tomography (HR-pQCT), our data suggest that anti-TNFα treatment prevents erosion progression and deterioration of bone microarchitecture within the first 3 months of treatment, one patient not responding to treatment, had significant progression of bone erosions within this short time period
There were 17 patients on anti-TNFα treatment combined with MTX treatment (6 with moderate, and 11 with high disease activity according to Disease activity score (DAS)-28-erythrocyte sedimentation rate (ESR) at baseline), while 9 patients were on MTX treatment only (MTX-only group) (4 in remission and 5 with low disease activity)

Summary

Introduction

One study showed minimal progression of erosions in patients with rheumatoid arthritis (RA) one year after TNFα inhibition therapy, no studies have investigated very early bone changes after initiation of anti-TNFα treatment. We investigated the effects of 3-month anti-TNFα treatment on bone erosion progression and bone microarchitecture in RA patients using high-resolution peripheral quantitative computed tomography (HR-pQCT). Tumor necrosis factor alpha (TNFα) is a proinflammatory cytokine involved in the pathogenesis of RA It induces the production and release of other proinflammatory cytokines (IL-1, IL-6, IL-8), and stimulates osteoclast activation in bone, eventually leading to bone erosions [3]. Anti-TNFα treatments have been shown to prevent erosion progression compared to a treatment with methotrexate (MTX) alone [4,5,6,7]. Either the radiography-based modified Sharp scores [4,5,6,7] or magnetic resonance imaging (MRI) was used to determine erosion progression [8, 9]

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