Bezsmertnyi I. Disorders of reparative osteogenesis of long bones with hyperhomocysteinemia and associated conditions (clinico-experimental study).

Українська версія

Thesis for the degree of Doctor of Science (DSc)

State registration number

0513U001146

Applicant for

Specialization

  • 14.01.21 - Травматологія та ортопедія

25-10-2013

Specialized Academic Board

Д 64.607.01

State institution "Sytenko Institute of Spine and Joint Pathology National Academy of Medical Sciences of Ukraine"

Essay

Object: reparative osteogenesis of long bones. Aim: to improve the efficiency of diagnosis and treatment disorders of reparative osteogenesis based on the study the effect of hyperhomocysteinemia and associated metabolic, vascular and molecular-genetic factors on the formation of nonunion of long bones. Methods: clinical and instrumental (radiography, computer tomography, ultrasound Doppler, ultrasound densitometry, X-ray intraosseous venography, pulseoximetry), biochemical (the study of indicators of bone metabolism, homocysteine, cytokines, lipid metabolism), molecular- genetic (polymorphism C677T MTHFR, C786T eNOS), morphological, pathophysiological (simulation of hyperhomocysteinemia), statistical methods. Statistical analysis was performed using programs "MS Excel XP" and "Statistica SPSS 10.0 for Windows" (number 305147890). The theoretical foundation of the features and trends, conservative and surgical treatment of disorders of reparative osteogenesis in hyperhomocysteinemia and associated metabolic, vascular and genetic factors on the based of clinical and experimental research has been made. The effect of the hyperhomocysteinemia, its combination with the inhibition of nitric oxide synthesis and correction means with hypohomocystinemic effect on biometric, biochemical and morphological parameters of bone, musculoskeletal system and peripheral vascular was investigated in the experiment .Role of hyperhomocysteinemia and associated metabolic and vascular disorders as the possible factors dysregeneration of long bone at model fracture was investigated. For the first time in Ukraine the prevalence of the genetic polymorphism of enzymes metabolic homocysteine and nitric oxide - metilentetrahydrofolatreductase (MTHFR C677T) and endothelial nitric oxide synthase (eNOS T786C) in healthy individuals, patients with consolidated fractures and false joints of long bones was investigated . Their relationship with the level of homocysteine, inflammatory markers, lipids, endothelial dysfunction was rated. The frequency of hyperhomocysteinemia, dyslipidemia, inflammatory markers (C-reactive protein, interleukin-6) and endothelial dysfunction in patients with consolidated fractures and false joints with unidentified factors disorders of reparative osteogenesis has been installed. The features of bone turnover markers with content bone destruction (pyridinoline, hydroxyproline, COMP, GAG), bone biosynthesis (СІСР, osteocalcin), the regulator of bone metabolism (TGF-?1), the frequency of osteopenia and osteoporosis in patiets with consolidated fractures and false joints of long bones have been identified and defined by their relationship with the level of homocysteine, markers of inflammation, endothelial dysfunction, genetic polymorphism MTHFR C677T and C786T eNOS. The metabolic and molecular-genetic predictors of disoder of reparative osteogenesis and the formation nonunion of long bones were identified, the most prognostically unfavorable combinations was defined. At experimental and clinical studies to the prevention of disorders of reparative osteogenesis means to hypohomocystinemic action and nitric oxide donors based. The study of the process regeneration of bone tissue at false joints against hyperhomocysteinemia and associated conditions has created a system of medical-rehabilitation measures to improve outcomes. Recommendations for the surgical treatment of nonunion of long bones at hyperhomocysteinemia and associated genetic diseases and metabolic disorders have been developed. The results of the work are the basis for applying the principles of personal trauma and allow to predict the course of reparative osteogenesis and choose the treatment depending the molecular- genetic and metabolic disorders. Study results were introduced in the work 32 medical facilities Vinnytsia , Volyn, Dnipropetrovsk , Zhytomyr, Ivano - Frankivsk, Kyiv , Kirovohrad, Luhansk, Lviv , Mykolayiv, Odesa , Poltava, Sumy, Ternopil and Chernihiv oblasts, the city of Sevastopol. Results of studies used in the educational process at the department of orthopedics and traumatology Vinnitsa national Pirogov memorial medical university of Health Ministry of Ukraine, the department of medical and social expertise and rehabilitation of State Estatablishment "Dnipropetrovsk medical academy of Health Ministry of Ukraine", in clinical practice of department orthopedic of Scientific research institute rehabilitation of Vinnitsa national Pirogov memorial medical university of Health Ministry of Ukraine, department of traumatology and orthopedics of Ukrainian scientific research institute of medical and social of invalid problems of Health Ministry of Ukraine. Traumatology and orthopaedy.

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