Background Vitamin D-resistant rickets is a systemic disease with impaired bone remodeling that interferes with orthopaedic treatment of musculoskeletal pathologies. There is a paucity of literature focusing on the content and dynamics in vascular endothelial growth factors (VEGF) that promote the transformation of cartilage to bone. Objective Explore blood serum concentration of VEGF and VEGF-А and their receptors VEGF-R2, VEGF-R3 at stages of combined osteosynthesis in patients with vitamin D-resistant rickets during correction of multiplanar deformities of lower limbs. Material and methods The study included 24 patients with multiplanar deformities of lower limbs secondary to vitamin D-resistant rickets. Patients were treated with combined Ilizarov external fixation and intramedullary nailing using hydroxyapatite-coated wires. Serum concentration of VEGF and VEGF-А and their receptors VEGF-R2, VEGF-R3 were measured during treatment. Values obtained in the patients were compared to reference levels measured in 180 somatically healthy individuals. The quantified results were presented in a percentage of the reference values. Results Preoperative serum VEGF and VEGF-R2 concentration was significantly higher in the patients than that in normal subjects: VEGF, by 1990 % (р = 0.0033); VEGF-A, by 450 % (р = 0.00042); VEGF-R2, by 392 % (р = 0.0052) while preoperative serum VEGF-R3 concentration was lower by 68 % (p < 0.05) in the patients than that in subjectively healthy individuals. Surgical treatment resulted in greater increase in VEGF, VEGF-A levels with maximal concentration observed at the distraction phase. The opposite dynamics was observed with VEGF-R2 receptor. Specific dynamics was noted with VEGF-R3 receptor during surgical correction. Nearly preoperative serum concentration of VEGF-R3 was seen at the first stage showing the lowest level (21% of the normal) during bone distraction with external fixator and regenerate formation. It was reduced by 25 % of the preoperative level at the end of treatment. Conclusion Patients with vitamin D-resistant rickets demonstrated strong imbalance in serum concentrations of VEGFs and their receptors. Phase opposition dynamics in serum concentrations of VEGFs and their receptors was detected during surgical correction of multiplanar deformities of lower limbs.
Наиболее важной задачей при дистракционном остеосинтезе является создание простых и эффективных способов контроля темпов дистракции позволяющих производить удлинение конечности в оптимальном режиме у различных групп пациентов. Цель исследования - анализ содержания сывороточных концентраций TGFb-1 и TGFb-2, BMP-4 и BMP-6 у лиц при увеличении роста с косметической целью и у пациентов с ахондроплазией на этапах дистракционного остеогенеза при удлинении голени методом Илизарова. Методика. Определение ростовых факторов проводили на комплексе оборудования фирмы Thermofisher (США): детектор Multiscan FC, встряхиватель iEMS, автоматический промыватель планшет WellWash. Для измерения концентрации факторов в сыворотке крови использовали наборы для иммуноферментного анализа (ИФА) eBioscience и RayBiotech Inc. (США). Результаты . Показано, что в сыворотке крови людей с ахондроплазией, еще до какого-либо ортопедического лечения концентрации TGF-b2 и ВМР-4, ниже, а TGF-b1 и ВМР-6, выше, чем концентрации этих факторов у людей при увеличении роста с косметической целью. У последних удлинение конечностей сопровождается возрастанием содержания в сыворотке крови факторов TGF-b1 и TGF-b2 на этапах начала и середины процесса дистракции. У пациентов с ахондроплазией, наблюдается обратная динамика: концентрация данных факторов (ВМР-4 и ВМР-3) в крови ахондропатов к концу дистракции увеличивается в 3,5 и 2 раза соответственно, снижаясь в периоде фиксации. Заключение. Таким образом, у пациентов с ахондроплазией происходит нарушение этапности процессов костного ремоделирования. Elaboration of simple and effective ways for managing the distraction rate to provide an optimum regimen of limb lengthening for different groups of patients is an important task in implementation of transosseous osteosynthesis. The aim of this study was to analyze blood serum concentrations of TGFb-1, TGFb-2, BMP-4, and BMP-6 in individuals undergoing cosmetic height increase and patients with achondroplasia at different stages of distraction osteogenesis in tibial lengthening using the Ilizarov method. Methods. Concentrations of growth factors were measured using a set of Thermofisher (USA) equipment, including a Multiscan FC detector, iEMS Shaker, and automatic WellWash Washer and ELISA kits (eBioscience and RayBiotech Inc., USA). Results. Serum concentrations of TGFb-2 and BMP-4 were lower and TGFb-1 and BMP-6 were higher in achondroplasia patients than in individuals with cosmetic height increase even before any orthopedic treatment. Long bone lengthening for cosmetic height increase was associated with increases in serum levels of TGFb-1 and TGFb-2 at the start and in the middle of distraction. In achondroplasia patients, opposite changes were observed; serum concentrations of BMP-4 and BMP-3 increased 3.5 and 2 times, respectively, by the end of distraction and decreased during fixation. Conclusion. Therefore, we observed a disorder of the stage-by-stage bone remodeling process in achondroplasia patients.
Purpose To compare and analyze structural changes in the vascular bed of the spine skin, paravertebral muscles in the zone of surgical intervention (at the apex of the spine deformity), as well as serum concentrations of vascular endothelial growth factors and their receptors in patients with kyphoscoliosis due to neurofibromatosis type I (NF-I). Material and methods The work is based on the results of examining a continuous cohort of patients with NF-I (n = 12). During the examination the concentrations of vascular endothelial growth factors (VEGF, VEGF-А, FGF-basic) and receptors for these factors (VEGF-R2, VEGF-R3) were determined in blood serum using the immunoenzyme analysis. Histological techniques of light and scanning electron microscopy were used for studying the biopsy material of the spine skin and paravertebral muscles obtained in the projection of the spine deformity apex during surgical correction of kyphoscoliosis. Results Concentration of VEGF and VEGF-A was 8 % (р = 0.00908) and 417 % (р = 0.00392) higher than reference values, respectively. VEGF-R2 receptor was 215 % (р = 0.00622) and exceeded the level of reference values. On the contrary, VEGF-R3 receptor concentration was 58.1 % (р = 0.00415), lower than the relative reference values. FGF-basic growth factor in blood serum was within control values (р = 0.05613). Changes in the histostructure of the vascular walls of largeand medium-size arteries and veins, fibrosis and obliteration of some vessel lumens, hyperemia of venous and capillary microvessels, formation of inflammatory infiltrates in adventitia of large-and medium-size vessels and in perivascular spaces, hemorrhages were revealed in bioptates of the spine skin. Pathological changes in muscles manifested themselves as fibrosis and constriction (up to complete obliteration) of the lumens of arterial vessels, increase in the diameter of thinwalled venous vessels, increase in their permeability leading to widespread extensive hemorrhages. Conclusion Increased concentration of vascular endothelial growth factors and their imbalance with receptors in patients with NF-I are combined with pathohistological structural changes in the vascular system of the spine skin and paravertebral muscles due to the inflammatory process present. The obtained results should be taken into account both in surgical treatment of this complex disease manifestations, and when planning treatment and rehabilitation measures in general.
бюджетное учреждение «Российский научный центр «Восстановительная травматология и ортопедия» им. акад. Г.А. Илизарова» Министерства здравоохранения Российской Федерации, г. Курган, Россия 2 Федеральное государственное бюджетное образовательное учреждение высшего образования «Тюменский государственный медицинский университет» Министерства здравоохранения Российской Федерации, г. Тюмень, Россия Vasodilator effect of vascular endothelial growth factors (VEGF) in the conditions of bone tissue formation by the method of discrete traction in congenital segmental pathology
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