Sykal O. Вone mineral density, risk fractures and reparative osteogenesis at type 2 diabetes mellitus (experimental and clinical research).

Українська версія

Thesis for the degree of Candidate of Sciences (CSc)

State registration number

0417U001286

Applicant for

Specialization

  • 14.01.21 - Травматологія та ортопедія

27-01-2017

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: structural-functional state of the bone, fracture risk and bone regeneration at type 2 diabetes mellitus. Objective: to evaluate bone mineral density, fracture risk in patients with type 2 diabetes mellitus and to examine features of reparative osteogenesis in experiment based on an assessment of structural and metabolic parameters of bone tissue. Methods: Dual energy X-ray absorptiometry (bone densitometer "Explorer QDR W"), algorithms FRAX and QFractureScore; experimental; morphological; biochemical; biomechanical. For the first time in women with diabetes type 2 diabetes mellitus, living in Ukraine, not only the normal values of bone mineral density have been found, but its decrease (in 48.8%), which conformed to osteopenia and osteoporosis. In women with type 2 diabetes mellitus a significant positive correlation between body mass index and bone mineral density in the lumbar spine and femoral neck was proved, but it was not found in the distal forearm. For the first time using the algorithms FRAX and QFractureScore it was found that the risk of fracture in women with type 2 diabetes mellitus is high in the vertebral bodies, radiation, humerus and femur (FRAX_Total), as well as in the femoral neck region (FRAX_Hip). Fracture risk indicators exceed the population indexes. In women with type 2 diabetes mellitus and normal bone mineral density clinically significant risk of fractures (FRAX_Total) was increased by 38.7%, and in the proximal femur (FRAX_Hip) - by 73.14% compared with control group. For the first time on the basis of complex research in animals with modeled type 2 diabetes mellitus against the background of hyperglycemia the abnormalities of lipid metabolism, damages of parenchyma liver and kidney, violation of metabolism of connective tissue and reduced bone strength has been found. It was proved that in animals with modeled type 2 diabetes mellitus bone remodeling was disturbed - bone formation was decreased and resorption process was enhanced. The disturbances of organic bone matrix was found. There were large areas with III type collagen, immature fibers composed of I type collagen. This leads to disruption of bone quality and reduce its strength. Increased excretion of hydroxyproline in the urine indicates catabolism of collagen. In animals with modeled type 2 diabetes mellitus the number of empty lacunae in the cortex and bone trabeculas of the femur was increased, the density of osteoblasts on the surface of bone trabeculas was reduced, the number of osteoclasts was increased. For the first time, based on the study of metabolic and morphological parameters of reparative osteogenesis in animals, that takes place against a background of type 2 diabetes mellitus and reduced bone mineral density, the main links of violations of bone quality which leads to a delay of regeneration, were revealed. Prerequisites for violation of reparative osteogenesis appear at an early stage: a reduction in the proliferation and differentiation of osteoblasts, decrease of angiogenesis, delay of the formation of tissue-specific structures of the regenerate. In the later stages of the low level of mineralization was observed. Violations of the organic bone matrix were identified: reducing refraction of sulfated glycosaminoglycans, type I collagen and the formation of regions with type III collagen. Increased excretion of calcium and hydroxyproline in the urine also reflects violation of the organic and mineral matrix of the regenerate. Patients with type 2 diabetes mellitus have a higher risk of developing of osteopenia and osteoporosis, so the study of bone mineral density and the risk assessment of clinically significant fractures should be included in the scheme of patient examination, because it was found that in patients with normal bone mineral density fracture risk may be increased. Identified metabolic and morphological disorders of reparative osteogenesis, leading to changes in the quality of bone, must be took into account in the postoperative management of patients with bone fracture to prevent violations of reparative osteogenesis. Results of the study werere introduced into clinical practice in SI "Sytenkо Institute of Spine and Joints Pathology National Academy of Medical Sciences of Ukraine", SI "V.Danilevsky Institute for Endocrine Pathology Problems of National Academy of Medical Science of Ukraine" The Ministry of Education and Science of Ukraine and in the educational process of the Department of Traumatology and Orthopedics of Kharkiv Medical Academy of Postgraduate Education Ministry of Health of Ukraine. Traumatology and orthopaedics.

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