Prospects for pharmacoprophylaxis of thromboembolic complications after total knee arthroplasty in patients with osteoporosis: clinical and pathogenetic aspects
- Authors: Vakhrushev N.A.1, Eliseeva E.V.2
-
Affiliations:
- Far Eastern District Medical Center of the Federal Medical and Biological Agency of Russia
- Pacific State Medical University
- Issue: Vol 32, No 8 (2025)
- Pages: 94-101
- Section: Articles
- URL: https://journal-vniispk.ru/2073-4034/article/view/365705
- DOI: https://doi.org/10.18565/pharmateca.2025.8.94-101
- ID: 365705
Cite item
Abstract
Background: Prevention of thromboembolic complications is a pressing issue in pharmacology. Its importance in orthopedics is driven by the increasing number of joint arthroplasties performed year after year. Existing thromboprophylaxis regimens and recommendations take into account many risk factors. However, a number of diseases and conditions whose role in the development of thromboembolic complications has not been fully elucidated. This study demonstrates the influence of hyperhomocysteinemia in osteoporosis on the incidence of these complications after total knee arthroplasty. The clinical and pathogenetic aspects of thrombosis development in this patient group are presented. Risk stratification for these complications is substantiated, with recommendations for prolonged pharmacoprophylaxis in patients with osteoporosis and hyperhomocysteinemia.
Objective: Evaluation of the influence of bone density on the development of venous thromboembolic complications after total knee arthroplasty (TKA).
Materials and methods: Eighty patients after total knee arthroplasty were examined. D-dimer levels were determined pre- and postoperatively using an immunoturbidimetric method. Plasma homocysteine levels were also measured using an enzymatic method. Bone mineral density was assessed using densitometry of the proximal femurs and lumbar spine. The results were evaluated using the T-score. Microsoft Excel 2016 and Statistica 10.0 were used for data processing.
Results: The study found that hyperhomocysteinemia occurred exclusively in the group of patients with osteoporosis. In patients with normal bone density and osteopenia, homocysteine concentrations did not exceed the reference range. Osteoporosis in patients is accompanied by higher mean preoperative homocysteine levels compared to patients with normal bone density and osteopenia. Women with osteoporosis and elevated homocysteine levels are at higher risk of thromboembolic complications after total knee arthroplasty. Group II patients with preoperative hyperhomocysteinemia who experienced thromboembolic complications after arthroplasty have a more pronounced increase in D-dimer levels on day 7 postoperatively. This may serve as a basis for revising existing thromboprophylaxis regimens quantitatively, with a view to prolonging the duration of anticoagulant treatment and qualitatively increasing the use of non-pharmacological thromboprophylaxis methods in patients of this group. Given the statistically significant higher incidence of VTEC after TKA, more careful patient selection for surgical treatment is necessary, with recommendations for treating this condition until the quantitative BMD indicator (T-score) improves to ≥-2.5 SD. This study found that hyperhomocysteinemia is not only an important predictor of osteoporosis and a risk factor for thrombosis, but also increases the incidence of VTEC after TKA in patients with osteoporosis. This phenomenon reflects the unfavorable course of osteoporosis associated with hyperhomocysteinemia and confirms several studies on the role of hyperhomocysteinemia in the pathogenesis of osteoporosis and thrombosis.
Conclusion. Given the obtained study results, further study of the impact of osteoporosis on the risk of VTEC after orthopedic surgeries other than TKA is necessary, including for the purpose of pharmacological correction of this pathology and identifying opportunities to supplement existing pharmacoprophylaxis regimens for this group of complications.
About the authors
Nikolay A. Vakhrushev
Far Eastern District Medical Center of the Federal Medical and Biological Agency of Russia
Author for correspondence.
Email: arthrologist@yandex.ru
ORCID iD: 0009-0004-6902-5596
SPIN-code: 6924-7597
Head of the Traumatology Department, Far Eastern District Medical Center of the Federal Medical and Biological Agency of Russia; Traumatologist-Orthopedist of the Highest Qualification Category, Chief External Expert in Traumatology and Orthopedics of the Federal Medical and Biological Agency for the Far East
Russian Federation, VladivostokEkaterina V. Eliseeva
Pacific State Medical University
Email: arthrologist@yandex.ru
ORCID iD: 0000-0001-6126-1253
SPIN-code: 1332-1667
Dr. Sci. (Med.), Professor, Head of the Department of General and Clinical Pharmacology
Russian Federation, VladivostokReferences
- Meng J., Liu W., Xiao Y. The role of aspirin versus low-molecular-weight heparin for venous thromboembolism prophylaxis after total knee arthroplasty: a meta-analysis of randomized controlled trials. Int J Surg. 2023;109(11):3648-3655. https://dx.doi.org/10.1097/JS9.0000000000000656
- van Es N., Takada T., Kraaijpoel N. Diagnostic management of acute pulmonary embolism: a prediction model based on a patient data meta-analysis. Eur. Heart J. 2023;44(32):3073-3081. https://dx.doi.org/10.3389/fcvm.2022.963528
- Eldibany M.M., Caprini J.A. Hyperhomocysteinemia and thrombosis: an overview. Arch Pathol Lab Med. 2007;131(6):872-884. https://dx.doi.org/10.5858/2007-131-872-HATAO
- Tøndel B.G., Morelli V.M., Hansen J.B., Braekkan S.K. Risk factors and predictors for venous thromboembolism in people with ischemic stroke: а systematic review. J Thromb Haemost. 2022; 20:2173–2186. https://dx.doi.org/10.1111/jth.15813
- Mouravas H., Verettas D., Kazakos K. Homocysteine and its relationship to deep venous thrombosis in patients undergoing total knee or hip arthroplasty. Hippokratia. 2010;14(3):185-188.
- van Meurs J.B., Dhonukshe-Rutten R.A., Pluijm S.M., et al. Homocysteine levels and the risk of osteoporotic fracture. N Engl J Med. 2004 May 13;350(20):2033-41. https://dx.doi.org/10.1056/NEJMoa032546
- Alkaissi H., McFarlane S.I. Hyperhomocysteinemia and accelerated aging: the pathogenic role of increased homocysteine in atherosclerosis, osteoporosis, and neurodegeneration. Cureus. 2023;15(7):e42259. https://dx.doi.org/10.7759/cureus.42259
- Gjesdal C.G., Vollset S.E., Ueland P.M. Plasma homocysteine, folate, and vitamin B 12 and the risk of hip fracture: the hordaland homocysteine study. J Bone Miner Res. 2007;22(5):747-756. doi: 10.1359/jbmr.070210
- Refsum H., Nurk E., Smith A.D. The Hordaland Homocysteine Study: a community-based study of homocysteine, its determinants, and associations with disease. J. Nutr. 2006;136 (6 Suppl): 1731S-1740S. doi: 10.1093/jn/136.6.1731S.
- Рубин М.П., Чечурин Р.Е. Двухэнергетическая рентгеновская абсорбциометрия осевого скелета: методика исследования, анализа и протоколирования. Радиология – Практика. 2001;2:34–41. [Rubin M.P., Chechurin R.E. Dual-energy X-ray absorptiometry of the axial skeleton: research, analysis, and recording methods. Radiology – Practice. 2001;2:34–41. (In Russ.)].
- Tinelli C., Di Pino A., Ficulle E. Hyperhomocysteinemia as a risk factor and potential nutraceutical target for certain pathologies. Front Nutr. 2019;6:49. https://dx.doi.org/10.3389/fnut.2019.00049
- Martínez-González J., Varona S., Cañes L. Emerging roles of lysyl oxidases in the cardiovascular system: new concepts and therapeutic challenges. Biomolecules. 2019;9(10):610. https://dx.doi.org/10.3390/biom9100610
- Nguyen P.K., Hall K., Holt I., Kuo C.K. Recombinant lysyl oxidase effects on embryonic tendon cell phenotype and behavior. J Orthop Res. 2023;41(10):2175-2185. https://dx.doi.org/10.1002/jor.25655
- Zhang J., Lu M., Guan X., et al. The role of lysyl oxidase in the pathological stage of atherosclerosis: structural stabilizer or disease driver? Curr Atheroscler Rep. 2025;27(1):69. https://dx.doi.org/10.1007/s11883-025-01312-z
- Jakubowski H., Witucki Ł. Homocysteine metabolites, endothelial dysfunction, and cardiovascular disease. Int J Mol Sci. 2025;26(2):746. https://dx.doi.org/10.3390/ijms26020746
- Behera J., Bala J., Nuru M. Homocysteine as a pathological biomarker for bone disease. J Cell Physiol. 2017;232(10):2704-2709. https://dx.doi.org/10.1002/jcp.25693
- Korzonek-Szlacheta I., Hudzik B., Nowak J. Mean platelet volume is associated with serum 25-hydroxyvitamin D concentrations in patients with stable coronary artery disease. Heart Vessels. 2018;33(11):1275–1281. https://dx.doi.org/10.1007/s00380-018-1182-9
- Dehghani K., Nowrouzi A., Pourdavood A.H., Rahmanian Z. Effect of vitamin D deficiency extremity and pulmonary venous thromboembolism. Biomed Res Ther. 2019;6(4):3107–3112. https://dx.doi.org/10.15419/bmrat.v6i4.535
- Wu W.X., He D.R. Low vitamin D levels are associated with the development of deep venous thromboembolic events in patients with ischemic stroke. Clin Appl Thromb Hemost. 2018;24(9_suppl):69S–75S. https://dx.doi.org/10.1177/1076029618786574
- Witucki Ł., Jakubowski H. Homocysteine metabolites impair the PHF8/H4K20me1/mTOR/autophagy pathway by upregulating the expression of histone demethylase PHF8-targeting microRNAs in human vascular endothelial cells and mice. FASEB J. 2024;38(18):e70072. https://dx.doi.org/10.1096/fj.202302116R
- Esse R., Barroso M., Tavares de Almeida I., Castro R. The contribution of homocysteine metabolism disruption to endothelial dysfunction: state-of-the-art. Int J Mol Sci. 2019;20(4):867. https://dx.doi.org/10.3390/ijms20040867
- Akhter M.S., Biswas A., Iqbal J. Endothelial nitric oxide synthase gene polymorphisms increase risk of deep vein thrombosis by altering homocysteine levels. Clin Lab. 2022;68(3). https://dx.doi.org/10.7754/Clin.Lab.2021.210642
- Lupi-Herrera E., Soto-López M.E., Lugo-Dimas A.J., et al. Polymorphisms C677T and A1298C of MTHFR Gene: homocysteine levels and prothrombotic biomarkers in coronary and pulmonary thromboembolic disease. Clin Appl Thromb Hemost. 2019;25:1076029618780344. https://dx.doi.org/10.1177/1076029618780344
- Munshi R., Panchal F., Kulkarni V., Chaurasia A. Methylenetetrahydrofolate reductase polymorphism in healthy volunteers and its correlation with homocysteine levels in patients with thrombosis. Indian J Pharmacol. 2019;51(4):248-254. https://dx.doi.org/10.4103/ijp.IJP_215_19
Supplementary files
