Longitudinal assessment of bone loss using quantitative ultrasound in a blood‐induced arthritis rabbit model

Wang, K. C.; Amirabadi, Afsaneh; Moineddin, Rahim; Jong, Roland; Tomlinson, Christopher; Doria, A.

doi:10.1111/hae.12743

Cited by 5 publications

(5 citation statements)

References 33 publications

(52 reference statements)

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“…Application of in vivo US in animal models of HA is a new area of investigation, with only few publications [15][16][17]. In the present study, US revealed joint pathology 14 days after induction of one or two joint bleeds, including oedema (soft tissue swelling), ligament swelling and disruption of the fat pad.…”

Section: Discussionmentioning

confidence: 48%

Visualization of haemophilic arthropathy in F8^−/− rats by ultrasonography and micro‐computed tomography

et al. 2016

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Section: Discussionmentioning

confidence: 48%

Visualization of haemophilic arthropathy in F8^−/− rats by ultrasonography and micro‐computed tomography

et al. 2016

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“…The following observed results also indicated pathogenesis similar to human RA. Thus, the choice of a rabbit model is suitable for research [ 23 ]. The lower price, suitable feeding, and molding were other factors influencing our experimental methods.…”

Section: Discussionmentioning

confidence: 99%

Value of Contrast-Enhanced Ultrasonography in Evaluating Rheumatoid Arthritis: Preliminary Research Based on an Animal Model

Gong

Huang

et al. 2021

Med Sci Monit

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Background The aim of this study was to evaluate the effectiveness of grayscale ultrasound (GSUS), power Doppler imaging (PDI), and contrast-enhanced ultrasonography (CEUS) in early rheumatoid arthritis (RA) diagnosis through animal experiments. Material/Methods A rabbit RA model was constructed. The animals were randomly divided into 2 groups, namely, the RA model group and the control group. GSUS, PDI, and CEUS were performed in the model group during early RA and were compared with pathology of synovial biopsies. The consistency of 3 types of ultrasonography was evaluated in tandem with pathological grading. Results 23 rabbits in the RA model group completed the experiment. GSUS showed that the synovial thickening of grades 1, 2 and 3 occurred in 12, 19, and 15 joints, respectively. The sensitivity, specificity, and accuracy of PDI in the diagnosis of knee joint synovitis in RA grades 1, 2, and 3 were 80.56% (29/36), 60.00% (6/10), and 76.09% (35/46), respectively, while those with CEUS were 94.44% (34/36), 90.00% (9/10), and 93.47% (43/46), respectively. The differences in diagnostic sensitivity, specificity, and accuracy of the 2 methods were statistically significant. Additionally, the thickness of the synovium measured with GSUS precontrast was greater than that of postcontrast. Conclusions RA evaluated with GSUS is often more hypertrophied than when evaluated with CEUS, while evaluation by PDI is less hypertrophied than that by CEUS. However, from a practical view point, GSUS and PDI are of sufficient practical value, except for in a few special cases.

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“…As described in previous studies [18, 28, 34, 35], for 8 weeks, intra-articular autologous blood injections were administered twice per week to create mild arthropathy in both knees of each rabbit in Group A. Intra-articular autologous blood injections were administered twice per week for 16 weeks to create severe arthropathy in both knees of each rabbit in Groups B and C (Fig. 1).…”

Section: Methodsmentioning

confidence: 99%

What is the Effect of Bevacizumab on Cartilage and Synovium in a Rabbit Model of Hemophilic Arthropathy?

Mert

Bılgıç

Şenol

et al. 2023

Clin Orthop Relat Res

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Background Hemophilic arthropathy can cause recurrent hemarthroses and severe damage to the synovium and articular cartilage. Previous studies have shown that vascular endothelial growth factor (VEGF) plays an essential role in neoangiogenesis. Bevacizumab, a monoclonal VEGF inhibitor, is used clinically to prevent angiogenesis. However, its effects on hemophilic arthropathy are unknown. Questions/purposes Using a hemophilic arthropathy rabbit model, we asked: Does an intra-articular injection of bevacizumab (1) inhibit VEGF, (2) decrease signal intensity in dynamic contrast-enhanced MRI (DCE-MRI) as an assessment of capillary permeability and neoangiogenesis, (3) reduce cartilage damage, (4) reduce synovial changes, and (5) affect macroscopic changes during the development of hemophilic arthropathy? Methods Twenty-five male New Zealand rabbits were divided into four groups. Eight knees from four rabbits were used as the control group. We used an established animal model for hemophilic arthropathy in the remaining 21 rabbits. Animals were assigned randomly to three groups with seven rabbits in each group. One group was used to establish mild arthropathy, and the other two were used to establish severe arthropathy. Autologous blood from the rabbits’ ears was injected into the right and left knees twice per week for 8 weeks to represent mild arthropathy and for 16 weeks to represent severe arthropathy. In the mild arthropathy group, bevacizumab was injected into the right knee once every 2 weeks. Bevacizumab was injected into the right knee of rabbits in one of the severe arthropathy groups once every 2 weeks for 16 weeks, and intra-articular bevacizumab injections were administered to the right knees of rabbits in the other severe arthropathy group once every 2 weeks after the eighth week. An equal volume of 0.9% saline was injected into the left knee of rabbits in all arthropathy groups. To explore the efficacy of bevacizumab, joint diameters were quantitatively measured, and cartilage and synovial changes were examined. Degeneration of articular cartilage was evaluated with the semiquantitative Osteoarthritis Research Society International grading system. Synovial damage was analyzed with a semiquantitative microscopic scoring system. In addition, we evaluated perfusion and angiogenesis using DCE-MRI (quantitative signal intensity changes). Immunohistochemical testing was used to measure VEGF levels (analyzed by Western blotting). Results Intra-articular bevacizumab treatment inhibited VEGF in our rabbit model of hemophilic arthropathy. VEGF protein expression levels were lower in the mild arthropathy group that received intra-articular bevacizumab (0.89 ± 0.45) than the mild arthropathy control group (1.41 ± 0.61) (mean difference -0.52 [95% CI -0.898 to -0.143]; p = 0.02). VEGF levels were lower in the severe arthropathy group that received treatment for 16 weeks (0.94 ± 0.27) than in the control knees (1.49 ± 0.36) (mean difference -0.55 [95% CI -0.935 to -0.161]; p = 0.01). In the severe arthropathy group, the Osteoarthritis Research Society International score indicating cartilage damage was lower in the group that received intra-articular bevacizumab treatment from the beginning than in the control group (median 17 [range 13 to 18] versus 18 [range 17 to 20]; difference of medians 1; p = 0.02). Additionally, the scores indicated synovial damage was lower in the group that received intra-articular bevacizumab treatment from the beginning than the control group (median 5 [range 4 to 9] versus 9 [range 8 to 12]; difference of medians 4; p = 0.02). The mean of mean values for signal intensity changes was higher in the nontreated severe groups than in the group of healthy knees. The signal intensity changes were higher in the severe arthropathy control groups (Groups BC and CC) (median 311.6 [range 301.4 to 361.2] and 315.1 [range 269.7 to 460.4]) than in the mild arthropathy control group (Group AC) (median 234.1 [range 212.5 to 304.2]; difference of medians 77.5 and 81, respectively; p = 0.02 and p = 0.04, respectively). In the severe arthropathy group, discoloration caused by hemosiderin deposition in the cartilage and synovium was more pronounced than in the mild arthropathy group. In the severe arthropathy group treated with intra-articular bevacizumab, joint diameters were smaller than in the control group (Group BT median 12.7 mm [range 12.3 to 14.0] versus Group BC median 14.0 mm [range 13.1 to 14.5]; difference of medians 1.3 mm; p = 0.02). Conclusion Hemarthrosis damages the synovial tissues and cartilage in the knees of rabbits, regardless of whether they are treated with intra-articular bevacizumab. However, intra-articular injection of bevacizumab may reduce cartilage and synovial damage in rabbits when treatment is initiated early during the development of hemophilic arthropathy. Clinical Relevance If the findings in this study are replicated in larger-animal models that consider the limitations of our work, then a trial in humans might be appropriate to ascertain whether intra-articular injection of bevacizumab could reduce cartilage damage and synovial changes in patients with hemophilia whose hemarthroses cannot otherwise be controlled.

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Longitudinal assessment of bone loss using quantitative ultrasound in a blood‐induced arthritis rabbit model

Cited by 5 publications

References 33 publications

Visualization of haemophilic arthropathy in F8^−/− rats by ultrasonography and micro‐computed tomography

Visualization of haemophilic arthropathy in F8^−/− rats by ultrasonography and micro‐computed tomography

Value of Contrast-Enhanced Ultrasonography in Evaluating Rheumatoid Arthritis: Preliminary Research Based on an Animal Model

What is the Effect of Bevacizumab on Cartilage and Synovium in a Rabbit Model of Hemophilic Arthropathy?

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Longitudinal assessment of bone loss using quantitative ultrasound in a blood‐induced arthritis rabbit model

Cited by 5 publications

References 33 publications

Visualization of haemophilic arthropathy in F8−/− rats by ultrasonography and micro‐computed tomography

Visualization of haemophilic arthropathy in F8−/− rats by ultrasonography and micro‐computed tomography

Value of Contrast-Enhanced Ultrasonography in Evaluating Rheumatoid Arthritis: Preliminary Research Based on an Animal Model

What is the Effect of Bevacizumab on Cartilage and Synovium in a Rabbit Model of Hemophilic Arthropathy?

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Visualization of haemophilic arthropathy in F8^−/− rats by ultrasonography and micro‐computed tomography

Visualization of haemophilic arthropathy in F8^−/− rats by ultrasonography and micro‐computed tomography