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

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 (R 2 = 0.311, p = 0.013; R 2 = 0.527, p = 0.003, respectively). In addition, erosion volume changes were significantly negatively correlated with changes in trabecular bone mineral density (R 2 = 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 (R 2 = 0.558, p < 0.001; R 2 = 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).

Bone changes assessed with High-Resolution peripheral Quantitative Computed Tomography (HR-pQCT) in early inflammatory arthritis: a 12-month cohort study

“…[38] Biologic DMARD-treated patients were more likely to demonstrate improvement in HR-pQCT outcomes, which is consistent with previous findings demonstrating decreases in erosion volumes under biologic therapies. [13,14,16] However, we did not observe any association with HR-pQCT outcomes and disease activity. The threshold for defining a significant change was based on precision of the outcomes at the 95% confidence level.…”

“…The initial disease course in RA is highly heterogenous; [11] predicting who may benefit from aggressive therapy is important to reduce medical risk and cost, as well as preserve function and productivity. [12] While HR-pQCT has been used to demonstrate repair effects at the group level, [13][14][15][16] to our knowledge, whether there is utility in monitoring progression with HR-pQCT in the early course of inflammatory arthritis has not been determined. Further, whether established risk factors for aggressive disease, including seropositivity, number of swollen joints and radiographic evidence of erosions [17][18][19][20] are also associated with progression of outcomes measured by HR-pQCT is not known.…”

High-Resolution Peripheral Quantitative Computed Tomography for Bone Evaluation in Inflammatory Rheumatic Disease

“…This study was conducted enrolling patients with RA and a mean disease duration of more than 5 years who were receiving either a TNF inhibitor (TNFi) in combination with methotrexate or methotrexate alone. While no significant changes in MRI outcome measures were observed, a significant increase in erosion volume assessed by HR-pQCT was observed for the methotrexate-treated patients, and those on combination therapy with treatment response had a demonstrated decrease in erosion volume (42). In this same study, joint space did decrease significantly in patients in combination therapy only.…”

“…Fifteen studies have reported longitudinal changes in the number and/or size of erosions. Of these, three investigated PsA (14,49,66), 10 investigated patients with RA (6,10,15,29,42,46,58,59,64,65), and one study examined ACPA+ individuals without arthritis (62). Seven studies investigated intervention with different therapies either as an open-label study or secondary analysis in a randomized controlled trial.…”

Structural Changes over a Short Period Are Associated with Functional Assessments in Rheumatoid Arthritis

“…Our group previously found that semiautomatic quantitative measurements of synovitis and bone marrow edema (BME) lesions in the wrist of patients with RA using 3 Tesla (3T) MRI showed excellent reproducibility and significant correlations with the standard RAMRIS score 18,19 . In addition to MRI, high-resolution peripheral quantitative computed tomography (HR-pQCT) is an emerging tool that provides a highly sensitive and reliable method to assess structural bone damage and joint space volume in patients with RA [20][21][22][23][24][25] . Therefore, combining MRI and HR-pQCT may help even more in evaluating structural and inflammatory joint abnormalities.…”