Inhibitory effects of dabigatran etexilate, a direct thrombin inhibitor, on osteoclasts and osteoblasts

Rocha, Amanda Leal; Bighetti‐Trevisan, Rayana Longo; Duffles, Letícia Fernanda; Arruda, José Alcides Almeida de; Taira, Thaise Mayumi; Assis, Bruna Rodrigues Dias; Macari, Soraia; Diniz, Ivana Márcia Alves; Beloti, Márcio Mateus; Fukada, Sandra Yasuyo; Goulart, Gisele Assis Castro; Ribeiro, Daniel Dias; Abreu, Lucas Guimarães; Silva, Tarcı́lia Aparecida

doi:10.1016/j.thromres.2019.12.014

Cited by 8 publications

(5 citation statements)

References 31 publications

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“…This is consistent with previous studies that reveal that 3D osteoblasts models when exposed to TiO 2 NPs, compared to monolayer cells, induce the secretion of vascular endothelial growth factor (VEGF), activating a cascade of events resulting in higher type I collagen production [ 39 , 40 , 41 , 42 , 43 ]. Bone mineralization is the first step for implant osseointegration and begins when collagen I acts as a three-dimensional scaffold for hydroxyapatite deposition [ 44 ]. Another study reported greater osteogenic differentiation when using 3D collagen gel culture [ 34 ].…”

Section: Discussionmentioning

confidence: 99%

The Effects of Titanium Dioxide Nanoparticles on Osteoblasts Mineralization: A Comparison between 2D and 3D Cell Culture Models

et al. 2023

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Although several studies assess the biological effects of micro and titanium dioxide nanoparticles (TiO2 NPs), the literature shows controversial results regarding their effect on bone cell behavior. Studies on the effects of nanoparticles on mammalian cells on two-dimensional (2D) cell cultures display several disadvantages, such as changes in cell morphology, function, and metabolism and fewer cell–cell contacts. This highlights the need to explore the effects of TiO2 NPs in more complex 3D environments, to better mimic the bone microenvironment. This study aims to compare the differentiation and mineralized matrix production of human osteoblasts SAOS-2 in a monolayer or 3D models after exposure to different concentrations of TiO2 NPs. Nanoparticles were characterized, and their internalization and effects on the SAOS-2 monolayer and 3D spheroid cells were evaluated with morphological analysis. The mineralization of human osteoblasts upon exposure to TiO2 NPs was evaluated by alizarin red staining, demonstrating a dose-dependent increase in mineralized matrix in human primary osteoblasts and SAOS-2 both in the monolayer and 3D models. Furthermore, our results reveal that, after high exposure to TiO2 NPs, the dose-dependent increase in the bone mineralized matrix in the 3D cells model is higher than in the 2D culture, showing a promising model to test the effect on bone osteointegration.

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Section: Discussionmentioning

confidence: 99%

The Effects of Titanium Dioxide Nanoparticles on Osteoblasts Mineralization: A Comparison between 2D and 3D Cell Culture Models

et al. 2023

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“…Significant findings can be achieved from in vitro studies employing DOACs and other anticoagulants in different bone cells, although here also, the results are controversial. Rocha et al 53 evaluated the effect of dabigatran (Pradaxa® capsule, Boehringer, Ingelheim am Rhein, Germany) on different cell cultures, including osteoclasts. Although heparin effects have been documented on osteoclasts, 54 data on DOAC effects are not yet available.…”

Section: Discussionmentioning

confidence: 99%

Effect of direct oral anticoagulant dabigatran on early bone healing: An experimental study in rats

Kyriakaki,

Karanikola,

Lillis

et al. 2023

J Adv Periodontol Implant Dent

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Background. Dabigatran belongs to the new generation of direct oral anticoagulants (DOACs). Its advantages are oral administration and no need for international normalized ratio (INR) monitoring. Although its use has increased, its potential side effects on bone healing and remodeling have not been fully investigated. The present study aimed to evaluate the possible effects of dabigatran on early bone healing. Methods. Sixteen male Wistar rats were divided into two groups; in group A, 20-mg/kg dabigatran dose was administered orally daily for 15 days, while group B served as a control. Two circular bone defects (d=6 mm) were created on either side of the parietal bones. Two weeks after surgery and euthanasia of the animals, tissue samples (parietal bones that contained the defects) were harvested for histological and histomorphometric analysis. Statistical analysis was performed with a significance level of α=0.5. Results. No statistically significant differences were found between the two groups regarding the regenerated bone (21.9% vs. 16.3%, P=0.172) or the percentage of bone bridging (63.3% vs. 53.5%, P=0.401). Conclusion. Dabigatran did not affect bone regeneration, suggesting that it might be a safer drug compared to older anticoagulants known to lead to bone healing delay.

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“…Anticoagulants have been previously reported to impair bone remodeling by inducing an imbalance between osteogenesis and osteolysis [40][41][42] . Recently, Rocha et al 43 reported that the oral anticoagulant dabigatran reduced osteoblast activity under optimal osteogenic conditions, including on titanium discs with a nanotopographic surface. Therefore, these observations suggest that anticoagulants may increase the revision rate by inducing osteolysis and impairing osseointegration of implants.…”

Section: Discussionmentioning

confidence: 99%

Long-Term Clinical Outcomes and Implant Survivorship of 151 Total Ankle Arthroplasties Using the HINTEGRA Prosthesis

Yoon

Park

et al. 2022

Journal of Bone and Joint Surgery

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Background: Few studies have investigated long-term clinical outcomes of a mobile-bearing total ankle arthroplasty (TAA) system. This study analyzed long-term outcomes of TAA using the HINTEGRA prosthesis at a single, non-developer center.Methods: Primary TAAs were performed on 213 ankles in 194 patients, and 151 consecutive ankles [71%] in 136 patients with a minimum follow-up of 10 years after the primary TAA were included in this study. Clinical results were assessed using a visual analog scale (VAS) pain score, the American Orthopaedic Foot & Ankle Society (AOFAS) Ankle-Hindfoot Scale score, the Ankle Osteoarthritis Scale (AOS) pain and disability subscores, and ankle range of motion. Prosthesis survivorship, reoperations, and risk factors were also evaluated. Results:The mean follow-up was 135.5 months (range, 120.0 to 204.0 months). All clinical scores and ankle range of motion improved significantly from preoperatively to 2 years, 4 to 6 years, and ‡10 years after TAA (p < 0.001). A total of 43 ankles (28.5%) required revision procedures, with the most common reason being periprosthetic osteolysis (32 ankles [21.2%]). The overall implant survivorship was 93.5% in Kaplan-Meier survival analysis at the mean follow-up of 11.3 years after the TAA.Conclusions: TAA using the HINTEGRA prosthesis with careful follow-up observation and appropriate adjunct procedures for the treatment of end-stage ankle arthritis produced satisfactory clinical results, which were maintained at a follow-up of ‡10 years, and resulted in 93.5% of implant survivorship.

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Inhibitory effects of dabigatran etexilate, a direct thrombin inhibitor, on osteoclasts and osteoblasts

Cited by 8 publications

References 31 publications

The Effects of Titanium Dioxide Nanoparticles on Osteoblasts Mineralization: A Comparison between 2D and 3D Cell Culture Models

The Effects of Titanium Dioxide Nanoparticles on Osteoblasts Mineralization: A Comparison between 2D and 3D Cell Culture Models

Effect of direct oral anticoagulant dabigatran on early bone healing: An experimental study in rats

Long-Term Clinical Outcomes and Implant Survivorship of 151 Total Ankle Arthroplasties Using the HINTEGRA Prosthesis

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