Systemic tranexamic acid promotes bone healing in a rat model of femur fracture

Karaduman, Zekeriya Okan; Arıcan, Mehmet; Turhan, Yalçın; Turhal, Ozan; Orhan, Zafer; Gamsızkan, Mehmet

doi:10.5606/ehc.2020.75430

Cited by 6 publications

(6 citation statements)

References 25 publications

(28 reference statements)

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“…In addition, TXA stimulated TNF-α and MMP-3 expression, as a positive effect in the early period of tendon healing [54]. Similarly, in an experimental rat model, TXA accelerated early bone formation and fracture healing of closed femoral fractures [55]. Ambra LF et al found that current TXA topical protocols (1, 2, and 4 mg/ml in saline solution) did not present any cytotoxic effects on cartilage explants in a pig model [56].…”

Section: Discussionmentioning

confidence: 96%

Peri-articular administration of tranexamic acid is an alternative route in total knee arthroplasty: a systematic review and meta-analysis

Fan

Liu

et al. 2022

J Orthop Surg Res

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Background As an antifibrinolytic agent, tranexamic acid (TXA) is increasingly used in total knee arthroplasty (TKA) to reduce blood loss. The administration of intravenous and intra-articular TXA has been well explored, but the most efficient way to administer TXA remains in question. Peri-articular injection (PAI) of TXA is a recently mentioned method. A meta-analysis of the efficacy of PAI TXA in patients after TKA should be performed. Methods A systematic search was performed within PubMed, Embase, and the Cochrane Library up to November 8, 2021. Two authors independently screened studies for eligibility and extracted data for analysis. The primary outcome was haemoglobin change. The secondary outcomes were haematocrit change, total drainage volume, thromboembolic events, and blood transfusion. Results A total of ten studies were included in this meta-analysis. The results indicated that there was a significant decrease in haemoglobin change when using PAI TXA compared with no TXA (mean difference − 1.05; 95% CI − 1.28 to − 0.81; P < 0.00001; I2 = 0%), but it had no significant differences compared with IA and IV (mean difference − 0.01; 95% CI − 0.17 to − 0.14; P = 0.85; I2 = 39%). There were no significant differences between the TXA < 1.5 g subgroup (0.10, 95% CI − 0.27 to 0.46; P = 0.60; I2 = 0%) and the TXA ≥ 1.5 g subgroup (0.18, 95% CI − 0.12 to 0.48; P = 0.24; I2 = 74%). In addition, the combined group (PAI plus IV or IA) was superior to the IV or IA group in terms of haemoglobin change (mean difference − 0.51; 95% CI − 0.76 to − 0.27; P < 0.0001; I2 = 19%). Regarding haematocrit change, the pooled result showed it was significantly less in the PAI group than the non-TXA group. Similarly, comparing it against the IV subgroup, the result revealed a difference in favour of the PAI group, with a mean difference of − 1.89 g/dL (95% CI − 2.82 to − 0.95; P < 0.0001; I2 = 67%). For total drainage volume, the pooled result was in favour of PAI TXA over no TXA (297 ml, 95% CI − 497.26 to − 97.23; P = 0.004; I2 = 87%), but it had no significant difference compared with IA and IV (mean difference − 37.98; 95% CI − 115.68 to 39.71; P = 0.34; I2 = 95%). There was no significant difference in thromboembolic events (OR 0.74; 95% CI 0.25 to 2.21; P = 0.59; I2 = 0%). Blood transfusion was not significantly different between the PAI group and the non-TXA group (OR 0.50; 95% CI 0.23 to 1.06; P = 0.07; I2 = 21%), and there was no significant difference between PAI and the other two TXA injection methods (OR 0.72; 95% CI 0.41 to 1.25; P = 0.24; I2 = 19%). Conclusion PAI has comparable effects to IV and IA injections. PAI is an alternative injection route of TXA for patients who have undergone TKA.

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Section: Discussionmentioning

confidence: 96%

Peri-articular administration of tranexamic acid is an alternative route in total knee arthroplasty: a systematic review and meta-analysis

Fan

Liu

et al. 2022

J Orthop Surg Res

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“…From radiological examination, we observed that fracture healing was statistically significant better at four and six weeks in the Theranekron groups. We believe that local hematoma, one of the fracture healing stages, stimulates angiogenesis through its stimulating effect on mesenchymal tissue and cytokines,[ 14 , 23 ] accelerating the osteogenesis stage.…”

Section: Discussionmentioning

confidence: 99%

“…Groups was designed as described Karaduman et al study. [ 14 ] Four separate groups were formed, with 12 rats in each group.…”

Section: Methodsmentioning

confidence: 99%

The effect of Theranekron on femur fracture healing in an experimental rat model

Güven

Özkan²,

Türközü³

et al. 2022

Jt Dis Relat Surg

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Objectives The aim of this study was to investigate the radiological, biomechanical, histopathological and immunohistochemical effects of Theranekron on fracture healing in an experimental rat model. Materials and methods Forty-eight male albino Wistar rats were used. Four groups were formed, with 12 rats in each of Theranekron groups 1 and 2, and control groups 1 and 2. After a fracture was created in the right femur of the rats included in the study, fixation was performed with an intramedullary Kirschner wire. Theranekron was administered subcutaneously to Theranekron groups 1 and 2 at a dose of 0.3 mg/kg on days 0, 5 and 10. After radiographic analysis of the femurs of Theranekron group 1 and control group 1 rats at four weeks of the study was performed, both groups were divided into two equal subgroups (six femurs in each group). Histopathological and immunohistochemical examinations were performed in one subgroup and biomechanical examination in the other subgroup. At the end of six weeks, the rats in Theranekron group 2 and control group 2 were evaluated after applying the same procedure as in the fourth week. Results When the mean radiological scores of the Theranekron and control groups were compared, a statistically significant difference was found in favor of the Theranekron group at four and six weeks (p=0.028 and p=0.006, respectively). At four weeks, statistically significant higher biomechanical forces were obtained in the Theranekron group compared to the control group (p=0.030). In the histopathological evaluation, the inflammation value of the control group at four weeks was statistically significantly higher than the Theranekron group (p=0.027). The angiogenesis, osteoblast proliferation, and bone formation values of the Theranekron group were significantly higher than the control group (p=0.014, p=0.014, and p=0.005, respectively). At six weeks, the bone formation values of the Theranekron group were statistically significantly higher than the control group (p=0.021). The difference between the Theranekron group and the control group scores of the immunohistochemical evaluation were statistically significantly different at four and six weeks (p=0.006 and p=0.011, respectively). Conclusion Theranekron may play a role in accelerating fracture healing by reducing acute inflammation process in the early period of fracture union, increasing fracture strength, angiogenesis, osteoblast proliferation, and bone formation.

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“…

Fracture healing is a dynamic process affected by many systemic and local factors. [1] It is vital for fracture healing that the blood supply is sufficient for crucial factors such as hormones, growth factors, and minerals to reach the fracture site. [1] Reduced fracture vascularity may result in a delayed bone union and atrophic non-union.

…”

mentioning

confidence: 99%

“…[1] It is vital for fracture healing that the blood supply is sufficient for crucial factors such as hormones, growth factors, and minerals to reach the fracture site. [1] Reduced fracture vascularity may result in a delayed bone union and atrophic non-union. Despite the developments in medical treatment methods, challenges related to the bone union are observed in 2 to 30% of fractures.…”

mentioning

confidence: 99%

Effects of different vardenafil doses on bone healing in a rat fracture model

Atçı

Alagöz²,

Saraç

et al. 2021

Jt Dis Relat Surg

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Objectives: We aimed to investigate the radiological, biomechanical, histopathological, histomorphometric, and immunohistochemical effects of different doses of vardenafil on fracture healing. Materials and methods: Fifty-one rats were divided into three groups. Group V5 was given 5 mg/kg/day of vardenafil; Group V10 was given 10 mg/kg/day of vardenafil; and the control group was given the same volume of saline. Six rats from each group were sacrificed on Day 14 (early period) and the remaining rats were sacrificed on Day 42 (late period). Callus/femoral volume and bone mineral density were measured using micro- computed tomography. Five femurs from each group in the late period were examined by biomechanical tests. In addition to the histopathological and histomorphometric evaluations, immunohistochemical analyses were performed to examine the levels of inducible nitric oxide synthase (iNOS), transforming growth factor-3 (TGF-β3), and nuclear factor kappa B (NF-κB) proteins. Results: Both doses of vardenafil increased primary bone volume and maximal bone fracture strength in late period, compared to the control group (p^lt;0.05). Histological healing scores of vardenafil groups were significantly higher in early period (p<0.001). While cartilaginous callus/total callus ratio in early period was higher, callus diameter/femoral diameter ratio in late period was lower in vardenafil groups (p<0.01). The NF-κB immunopositivity in V10 group decreased in early period, compared to control group (p<0.001). The TGF-β3 and iNOS immunopositivity increased in both V5 and V10 groups, compared to the control group in early period, but returned to normal in late period. Conclusion: During the first period of fracture healing process in which vasodilation is mostly required with increasing inflammation, vardenafil has ameliorating effects on the bone union and supports fracture healing.

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Systemic tranexamic acid promotes bone healing in a rat model of femur fracture

Cited by 6 publications

References 25 publications

Peri-articular administration of tranexamic acid is an alternative route in total knee arthroplasty: a systematic review and meta-analysis

Peri-articular administration of tranexamic acid is an alternative route in total knee arthroplasty: a systematic review and meta-analysis

The effect of Theranekron on femur fracture healing in an experimental rat model

Effects of different vardenafil doses on bone healing in a rat fracture model

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