Peculiarities of Reparative Osteogenesis in Fractures of the Proximal Femur in Patients with Concomitant Arterial Hypertension

Treatment of patients with fractures of the proximal femur is an important problem in modern traumatology. Hip fractures are more commonly associated with osteoporosis. Elderly and senile people make up a significant proportion of patients with fractures. Arterial hypertension (AH) in the elderly population is a disease with a high prevalence. When treating fractures of the proximal femur, it is necessary to take into account the features of reparative osteogenesis characteristics of patients with concomitant arterial hypertension. Medicines used to treat hypertension have a beneficial effect on bone tissue. Pharmacological correction of hypertension in these patients is essential to optimize fracture healing.

Comparative analysis of local stimulation methods of reparative osteogenesis

Objective To determine the ratio of the main growth factors when using various methods of local stimulation of reparative osteogenesis.Material and methods The study consisted of two parts: in the first part a comparative analysis of the content of growth factors by ELISA was carried out (PDGF – platelet derived growth factor, TGF – transforming growth factor, VEGF – vascular endothelial growth factor, IGF – insulin-like growth factor, BMP6 and BMP7 – morphogenetic proteins 6 and 7), capable of stimulating reparative osteogenesis in blood plasma, plateletrich plasma, red bone marrow and bone autoregenerate. The second part presented the results of approbation of the autoregenerate obtained according to the original method in the framework of an acute experiment on animals.Results The most important cytokines affecting the process of reparative osteogenesis are fibroblast growth factor – FGF1 and bone morphogenetic protein 7 – BMP7. Based on the results of a comparative enzymelinked immunosorbent assay, it has been established that the autoregenerate, obtained by the original method, and a bone marrow aspirate concentrate have the highest osteogenic potential.Conclusion Autoregenerate is an effective and promising means of local stimulation of reparative osteogenesis, and its transplantation is a simple and highly effective procedure.

Dynamics of hematological parameters in rabbits for osteosubstitution by hydroxyapatite ceramics doped with germanium and in complex with blood coagulation activator

Bone tissue has powerful regenerative properties, thanks to which, with stable fixation, quite large amounts of skeletal bone damage can be successfully repaired. However, in the case of fragmentary fractures, the use of osteosynthesis methods alone does not always ensure the optimal course of reparative regeneration, as its regenerative potential is lost. Therefore, there is a need to replace post-traumatic bone defects and stimulate reparative osteogenesis. For this purpose, doped or doped with various elements (Ge, Si, Zn, Ag, Cu) composite materials. The aim of the study was to investigate the dynamics of hematological parameters in rabbits for osteosubstitution by hydroxyapatite ceramics doped with germanium and in combination with a blood clotting activator. Model defects were formed in the radial diaphysis and femur metaphysis in rabbits with a 3 mm and 4.2 mm diameter drill bit, respectively. Anesthesia included acepromazine, thiopenate, and lidocaine infiltration anesthesia. Animals of the first experimental group (n = 12) were replaced by defects with granules of hydroxyapatite ceramics doped with germanium (HTGe), the second (n = 12) – hydroxyapatite ceramics doped with germanium with blood coagulation activator (HTGe + a), the third – (n = 12). hydroxyapatite α + β with active (α + β + a), and control – granules of undoped ceramics (HT). On day 7, animals of all groups had minor post-traumatic erythrocytopenia and oligochromemia. There was also a gradual increase in the content of leukocytes in the blood with a peak on the 14th day, which in the group HTGe + a lasted until the 30th day. The increase in the number of leukocytes and their peak values occurred within the physiological norm and only approached its upper limit. In most groups there was a pronounced thrombocytosis during the first 14 days with normalization to the 30th day, but in the 2nd experimental group the number of platelets returned to normal only on the 60th day. Changes in most integral hematological indices, which reflect the relationship between blood cell populations, are characteristic of the inflammatory-resorptive phase of reparative osteogenesis. The dynamics of hematological parameters indicates the absence of a pronounced reaction of the body to the implantation of hydroxyapatite composite doped with germanium. The combination of hydroxyapatite ceramics doped with germanium with coagulation activator eliminates post-traumatic oligochromemia and erythrocytopenia and significantly increases the level of hematological integral indices, which indicates a more intensive course of inflammatory-resorptive clinical resorptive aparation phase.

Histomorphological characteristics of bone replacement in rabbits with hydroxyapatite ceramics and Platelet-Rich Fibrin

The results of a histomorphological study of bone regenerates in rabbits after osteosubstitution with platelet-rich fibrin and its combination with hydroxyapatite granules with β-tricalcium phosphate in spongy and compact bone tissue at different periods of reparative osteogenesis are presented. Three groups of rabbits were formed. In the control group, the defects were left to heal under the blood clot. Bone lesions in the first experimental group were filled with platelet-rich fibrin, in the second – with a combination of platelet-rich fibrin and hydroxyapatite with β-tricalcium phosphate. All animals were kept in the same conditions of feeding and housing, had unlimited access to water. During the study, the rabbits were monitored clinically. The animals were taken out of the experiment on the 14th, 21st and 42nd days, samples of bone tissue were taken, they were fixed, decalcified, dehydrated in alcohols of increasing concentration and embedded in paraffin. In the presented study, it is most likely that the newly formed bone tissue is formed precisely due to osteoinduction in the experimental groups. When using granules of hydroxyapatite and β-tricalcium phosphate with platelet-rich fibrin, bone regenerate is between the composite granules and is not associated with contact with the maternal bone. Its cells appear in different places of the defect. In the spongy bone tissue on the 21st day, regeneration proceeded more fully and faster in the second experimental group, as evidenced by the significant density of cells of the osteoblastic row, the thickness of the bone trabeculae and their volume, filling the site of the defect. On the 42nd day, in the second experimental group, when using a combination of autobiomaterial and hydroxyapatite granules with β-tricalcium phosphate, the regenerate contained a significantly larger number of osteogenic cells in the thickness of the trabeculae, which indicated a more intensive course of reparative osteogenesis in comparison with the first experimental and control groups. In the compact bone on day 21, regeneration was more complete and faster in the second experimental group. On the 42nd day, according to the degree of maturity of the bone regenerate, calcium-phosphate ceramics in combination with platelet-rich fibrin optimizes reparative osteogenesis most clearly. According to the degree of intensity of the osteoregeneration process, the groups can be placed in the following sequence: control ˂PRF˂PRF+HA/β-TCP–700. According to histomorphological characteristics, the combination of hydroxyapatite with β-tricalcium phosphate and platelet-rich fibrin gives greater osteoinduction to the composite material, which is confirmed by the high cell density, namely of osteoblasts and osteocytes. The use of PRF in combination with other materials may become promising for the correction of reparative osteogenesis in conditions of limited or reduced regenerative potential of bone tissue.

Dynamics of cytokines in osteosis splinter fractures replacement in dogs with hydroxyapatite ceramics silicon-doped

Among the entire public of fractures of long bones, more complications of reparative osteogenesis occur fragmental fractures. Their significant defects, which arise as a result of the removal of non-viable fragments, cause disturbances in local hemodynamics and microcirculation and loss of osteoconduction in the area of injury, lead to a loss of the reparative potential of bone tissue in the defect zone, and the methods of osteosynthesis do not provide restoration of osteoconduction and do not have osteointegration properties. For osteosis, a number of composite materials have been proposed, among which ceramics based on calcium phosphates are considered the most promising, which is confirmed by previous clinical, radiological and histomorphological studies. The aim of the study is to determine the dynamics of the blood levels of TGF-β and interleukins IL-1β and IL-10 for osteosis replacement of splinter bone fractures in dogs with calcium phosphate ceramics doped with silicon. Material and research methods: a control (n = 7) and research group (n = 7) dogs with accidental splinter fractures of long bones were formed. In both groups, extracortical osteosynthesis was performed with a support plate from an unalloyed titanium alloy. In the control group, bone defects were left to heal under a blood clot, and in the experimental group they were replaced with ceramics (GTlKg-3). Blood samples were taken after trauma no later than on the 48th day, and on the third, twelfth, twenty-first, forty-second and 60th days after surgical treatment. The enzyme immunoassay was used to determine the serum levels of interleukins IL-1β and IL-10 and transforming growth factor (TGF-β) тhat for a bureta reaction is a bit of a home-made bottle. The study results showed an anti-inflammatory cytokine profile with physiological norms in dogs. In case of bone injury, it becomes pro-inflammatory in nature, triggers the process of osteoresorption in the fracture area. At the same time, during reparative osteogenesis after extracortical osteosynthesis for splinter fractures, proinflammatory cytokinemia acquires a permanent character with a peak on the forty-second day, and this implies inhibition of metaplasia of cartilaginous regenerate into bone, that is, it slows down the consolidation of the fracture. However, in the case of osteosis with ceramics, the level of pro-inflammatory cytokinemia is significantly lower and continues during the first 12 days with a peak on the third day, during the inflammatory-resorptive stage. However, the key in understanding the effectiveness of osteosis was the dynamics of TGF-β, which showed its biphasic hyperreactivity in control animals, while in experimental animals, its balanced production was noted. Conclusion. Osteosis replacement of bone defects in long tubular bones in dogs with hydroxyapatite with β-tricalcium phosphate ceramics doped with silicon is accompanied by moderate cytokinemia in accordance with the course of the inflammatory-resorptive stage and the phase of remodeling with a peak of induction of transforming growth factor during the period of active osteogenesis forty-second course of reparative osteogenesis.

Dynamics of biochemical bone and endothelial parameters during the replacement of bone defects in dogs with hydroxyapatite ceramic doped with silicon

Metal structures for osteosynthesis available in veterinary orthopedics are not able to compensate for the lost elements of bone tissue in complex splinter fractures. It is prompt the use of hydroxyappatite materials that replaced bone defects for maintenance of osteoconductive function, and ideally would combine osteointegration and osteoinductive properties. However, their influence on the biological processes of fracture consolidation which go through a number of successive stages and end with the formation of bone tissue in the fracture zone identical to the maternal, is insufficiently substantiated according to the criteria of the molecular biological phase of reparative osteogenesis. The aim of the study was to investigate the dynamics of biochemical osteotropic parameters and the level of NO using silicon-doped ceramics for fractures heeling in dogs. Materials and methods. The animals suffering of fractures that were admitted to the faculty clinic were divided into control (n=7) and experimental (n=7) groups. In both groups, extracortical osteosynthesis was performed with a support plate from an unalloyed titanium alloy. In the control group, bone defects were left to heal under spontaneous blood clot, and in the experimental group, they were replaced with ceramic based on hydroxyapatite with β-tricalciumphosphate doped with silicon (HA/β-TCP/l-Si–3).Blood samples were taken after the injury no later than the 48th day, and on the 3th, 12th, 21th, 42th and 60th days after osteosynthesis. To increase the objectivity of the biochemical analysis, we additionally formed a group of clinically healthy dogs that were admitted to the clinic for routine vaccination (n=10). It included the spectrophotometric determination of the content of NO, BALP, TRACP, Ca, P, Mg, total protein in blood serum, and fibrinogen in blood plasma. Research results. A clinical study showed that in the case of using HA/β-TCP/l-Si–3for splinter fractures, the stages of reparative osteogenesis are more optimized in time, and their consolidation occurs on average 19 days earlier than in the control group. The results of the biochemical study showed that when using HA/β-TCP/l-Si–3, it is accompanied by a peak NO value already on the third day, which is significantly higher than in the control group and indicates early angiogenesis in the research group. In terms of TRACP, the period of osteoresorption in the control group was permanent with little expressed peaks of activity. However, in the research group, the peak of TRACP activity is limited to 12 and 21 days, which is evidence of an optimized inflammatoryresorptive phase. In parallel with this, the activity of BALP increases, which indicates the consistency of the stages of reparative osteogenesis and provides an optimized and accelerated consolidation of fractures in the research group. Conclusion. The dynamics of NO, BALP and TRACP pathochemically substantiates the optimized reparative osteogenesis when using HA/β-TCP/l-Si–3 for bone defects replacement in cases of splinter fractures of tubular bones. Key words: bone markers, bone isoenzyme of alkaline phosphatase, NO, tartrate-resistant acid phosphatase, fibrinogen, calcium, phosphorus.

SOME ASPECTS OF MAXILLOFACIAL SURGERY OF SMALL NONPRODUCTIVE ANIMALS

An analytical review is presented, the purpose of which is todetermine the most important vectors when choosing approaches to reparative osteogenesis in dogs and cats with fractures of the bones of the upper and / or lower jaw. Medical care for all types of fractures should rely on such vectors of functionally stable osteosynthesis as adequate rigid fixation, minimally invasiveness, structural stability, safety and effectiveness of the new product's effect on bone regeneration and on the whole organism as a whole.

X-ray and macromorphological evaluation of reparative osteogenesis by implantation of hydroxyapatite composite doped with germanium

Fragmentary fractures require not only the use of complex methods of osteosynthesis, but also the replacement of the defect site with implants to optimize reparative osteogenesis. A large number of osteosubstitute materials are used, including hydroxyapatite ceramics. To enhance its osteointegration properties, microelements with osteoinductive properties are added. The aim of the work is X-ray and macromorphological evaluation of the influence of hydroxyapatite ceramics doped with germanium on reparative osteogenesis in model fractures of the femur and radius in rabbits. Model defects were formed in the radial diaphysis and femur metaphysis in rabbits with a drill with a diameter of 3 mm and 4.2 mm, respectively. Anesthesia included acepromazine, thiopenate, and lidocaine infiltration anesthesia. In the experimental group (n=12) defects were replaced by granules of hydroxyapatite ceramics doped with germanium, and in the control group (n=12) – undoped. The use of hydroxyapatite ceramics doped with germanium is accompanied by a moderate course of the inflammatory-resorptive phase of reparative osteogenesis. At the same time on the radiographs of animals of the experimental group on the 14th day the periosteal reaction is moderate, and on the 30th day it is barely noticeable with increased radiological density. In control animals after trauma to the compact bone proximal and distal to its location showed a thickened and compacted periosteum with a contrasting composite material. On the 60th day in the cancellous bone of experimental animals, the area of injury acquired an X-ray density close to normal, in the control – it remained elevated. Hydroxyapatin composite doped with germanium acquires osteoinductive properties and may be promising for the replacement of bone defects and correction of reparative osteogenesis in animals. Key words: bioceramics, germanium, bone fractures, compact and spongy bone tissue, rabbits.

Bone remodeling in patients with type I and type II diabetes mellitus in pre- and postmenopausal periods

Aim: to perform structural and functional analysis of the activity of reparative osteogenesis processes at pre- and postmenopausal women with diabetes mellitus (DM).Materials and Methods. There were enrolled 142 pre- and postmenopausal patients with type I and type II diabetes mellitus type (DM-1 and DM-2) as well as 43 females in control group. Subjects taking medicines acting on bone metabolism comorbid with chronic diseases were excluded from the study. All patients underwent Dual-energy X-ray Absorptiometry (DXA) to assess bone mineral density (BMD, T-score). Serum markers of bone remodeling (alkaline phosphatase, ALP; procollagen type I N propeptide, PINP; beta-Cross laps, b-CTx), metabolic and hormone parameters (glycated hemoglobin, parathyroid hormone, calcitonin, vitamin D, electrolytes) were also measured.Results. A positive correlation was found between the duration of DM-1 and DM-2 and b-CTx level (DM-1: г = 0.349, р = 0.08; DM-2: г = 0.214, р = 0.04). A negative correlation was found between the lumbar spine T-score and the duration of diabetes (DM-1: r = -0.568, p = 0.001; DM-2: r = -0.267, p = 0.04). A statistically significant correlation was found between the lumbar spine T-score and b-CTx levels (DM-1: r = -0.452, p = 0.002; DM-2: r = -0.357, p = 0.09).Conclusion. The results of current study suggest that reparative osteogenesis in patients with post-menopausal DM-1 vs. DM-2 and the control group was moderately increased. In patients with DM-2, a less pronounced change in BMD was determined in parallel with inconsistent bone remodeling processes, which casts doubt on the ability of DXA to predict fractures in these patients. Such changes contribute to decreased bone quality, which distinguishes diabetic osteopathy from traditional menopausal osteoporosis manifested mainly by low BMD.