Carbon-carbon composite nail for intramedullary osteosynthesis in rats with experimental osteoporosis

Background. In Ukraine, there has recently been an increase in the number of limb bone fractures among the population, in particular, due to increase in the number of elderly people, which is associated with the development of age-related osteoporosis and fragility of bones. Therefore, the use of artificial implants in traumatology is becoming increasingly important. The search for new bioinert and biodegradable materials, that are capable of providing rapid fracture consolidation and do not require repeated surgical intervention, continues. Objective. To elaborate a model for the research of using carbon-carbon composite nail for intramedullary osteosynthesis in laboratory rats with fractures of femur and tibia in norm and with experimental osteoporosis. Methods. The work investigated the lower limbs of 6 groups of Wistar rats. The first part of the study involved 4 groups of rats with modeled tibial fracture with subsequent osteosynthesis in norm and with experimental osteoporosis. The second part of the research included two groups of laboratory rats with modeled femur fracture. In both parts we used metal injection needle, as well as carbon-carbon composite nail for osteosynthesis. Results. All animals underwent surgery well, stepped on the injured limb. X-ray examination after the osteosynthesis demonstrated satisfactory reposition of the fragments. One month after modeled fracture in rats with experimental osteoporosis a violation of the normal consolidation of the fracture was observed, especially in the group where carbon-carbon composite nails were used for osteosynthesis. Further, until the 180th day after the surgery there were no peculiarities, function of the limbs was restored, mainly without expressed angular deformities. Conclusion. The above mentioned model was successfully elaborated for the research of using carbon-carbon composite nail for intramedullary osteosynthesis in laboratory rats with fractures of femur and tibia in norm and with experimental osteoporosis.

Bichasic calcium phosphate bioceramic materials influence on osteoporotic bone biomechanical parameters and bone density (experimental research). Summary of the Doctoral Thesis

Bone regeneration is a physiological process of bone formation that occurs during normal fracture healing and is involved in a continuous process of bone remodeling during life. However, there are a variety of clinical conditions that require extensive bone regeneration, such as osteoporotic bone fractures. Calcium phosphate containing biomaterials, such as hydroxyapatite, which can be in pure form or coated with drugs, is one of the best known and clinically researched bone regeneration products. Biphasic calcium phosphate bioceramics is used as a bone substitute to improve osteoporotic bone properties and promote bone healing. Strontium-containing calcium phosphate bone cements are promising materials for the recovery of bone defects associated with osteoporosis, as they stimulate bone formation and at the same time limit the activity of osteoclasts.The aim of the study was to determine the changes in bone mineral density, biomechanical and morphological properties after local amplification of the trochanter major area of the femur with biphasic calcium phosphate bioceramic materials in rabbits with experimental osteoporosis.The study used 34 eight month old female experimental animals - rabbits, 24 of which developed experimental osteoporosis after ovariectomy and subsequent injection of methylprednisolone. There were 10 healthy rabbits in the control group. Non-commercial biomaterials produced at the Riga Technical University Rudolfs Cimdins Riga Biomaterials Innovation and Development Center were used for the study - biphasic calcium phosphate bioceramics ? calcium hydroxyapatite (HAP) and tricalcium phosphate (TCP) in the ratio of 70/30. Rabbits affected by osteoporosis were divided into groups and the defect in the right (operated) femur was filled with HAP/TCP granules with or without 5% Strontium (Sr) or left blank as a placebo surgery group.To demonstrate osteoporosis by morphological examination, 10 samples of the mandibular premolar region were taken from healthy (control) rabbits and 23 samples of the mandibular premolar region from rabbits with experimental osteoporosis. To determine the local effects of biomaterials, 23 samples of the right (operated) femur, 23 samples of the left (non-operated) femur and 23 samples of mandibular angle from rabbits with experimental osteoporosis were used to determine the systemic exposure of biomaterials by biomechanical and radiological methods.In the cross-section of the mandibular bone, the trabecular bone area in the control group was 0.20 mm^2 (0.176–0.233 mm^2), which is statistically significantly higher than in the osteoporotic groups (HAP/TCP group (0.127 mm^2; 0.118–0.149 mm^2), HAP/TCP/5 % Sr group (0.136 mm^2; 0.108?0.166 mm^2) and placebo surgery group (0.135 mm^2; 0.126?0.164 mm^2)).Within the framework of the study, a three-point bending test was performed to determine biomechanical parameters of bone tissue. During bending, the destructive stress and destructive deformation were determined for each specimen. The hardness of the specimens was expressed as the modulus of elasticity. The destructive deformity of the operated, non-operated femur and mandibular bone samples after implantation of HAP/TCP biomaterial with or without 5 % Sr was statistically significantly lower compared to the destructive deformation of the samples in the placebo surgical groups. The destructive stress of non-operated femoral specimens after implantation of HAP/TCP biomaterial with or without 5 % Sr was statistically significantly higher compared to the destructive stress of samples in the placebo surgical group. No statistically significant differences were found between bone samples from the operated femur and mandible bone placebo surgery groups and bone samples after implantation of HAP/TCP biomaterial with or without 5 % Sr. The modulus of elasticity of operated, non-operated femur and mandibular bone samples after implantation of HAP/TCP biomaterial with or without 5 % Sr was statistically significantly higher compared to the modulus of elasticity of placebo surgery groups samples.The mineral density of operated, non-operated femur and mandibular bone samples after implantation of HAP/TCP biomaterial with or without 5 % Sr was statistically significantly higher compared to the mineral density of samples from placebo surgery groups, which indicates the effect of systemic biomaterials on bone of experimental animals. This opens up the prospect of the use of biomaterials for the treatment and prevention of osteoporosis.No statistically significant differences were found between the destructive deformation, destructive stress, flexural modulus and mineral density of operated and non-operated femur specimens after HAP/TCP and HAP/TCP with 5 % Sr biomaterials, indicating the same effect of biomaterials on the bone tissue of experimental animals remotely from the implantation site. Analyzing the biomechanical parameters of osteoporotic bone samples after implantation of HAP/TCP biomaterial with or without 5 % Sr, only statistically significant changes in all biomechanical parameters were observed for operated femur bone samples, indicating the promotion of bone strength in the presence of Strontium. No statistically significant differences were found in the biomechanical parameters of non-operated femur samples, as well as in the destructive deformation and modulus of elasticity of the mandibular bone samples between the HAP/TCP and HAP/TCP 5 % Sr groups. Also, no statistically significant differences were found in the mineral density of operated, non-operated femur and mandibular bone samples between the HAP/TCP and HAP/TCP 5 % Sr groups. Further studies with higher levels of Strontium in the biomaterial may be required to achieve a clinical effect.

Possibilities of in vivo validation of a model of experimental osteoporosis

In this work, the possibilities ofin vivovalidation of an experimental model of osteoporosis are analyzed. Themodel is based on the application of biochemical methodsforanalyzing predictors of osteoporosis inbloodserum,andtheirinformative value in the comparativeanalysis of the assessment of the degree of osteoporosisbasedoninstrumental studies of autopsy of bone tissue usingatomicabsorption spectroscopy and x-ray densitometry.

Possibilities of in vivo validation of a model of experimental osteoporosis

In this work, the possibilities ofin vivovalidation of an experimental model of osteoporosis are analyzed. Themodel is based on the application of biochemical methodsforanalyzing predictors of osteoporosis inbloodserum,andtheirinformative value in the comparativeanalysis of the assessment of the degree of osteoporosisbasedoninstrumental studies of autopsy of bone tissue usingatomicabsorption spectroscopy and x-ray densitometry.

The Beneficial Effect of Boswellic Acid on Bone Metabolism and Possible Mechanisms of Action in Experimental Osteoporosis

Estrogen is instrumental in the pathological process of osteoporosis because a deficiency of this hormone increases the release of bone-resorbing cytokines. Acetyl-11-keto-β-boswellic acid (AKBA), a constituent from Boswellia serrata, has an anti-inflammatory effect by inhibiting tumor necrosis factor-α (TNF-α) expression, which leads to a decline in receptor activator of nuclear factor-kappa B (NF-κB) ligand, and consequently, a reduction in osteoclast activity. Hence, AKBA may be beneficial against bone loss during osteoporosis. Therefore, the current study intended to evaluate the beneficial effects of AKBA in ovariectomy-induced osteoporosis and to investigate its mechanism of action. Sham-operation or ovariectomy female Sprague Dawley rats were used for evaluating the antiosteoporotic effect of AKBA in this study. AKBA (35 mg/kg, p.o.) and estradiol (0.05 mg/kg, i.m.) were administered for 42 days. At the end of the experiment, body and uterus weights, serum and urine calcium and phosphorus, serum alkaline phosphatase, and urinary creatinine levels, besides serum levels of NF-κB and TNF-α were determined. Weight, length, thickness, hardness, calcium content, as well as the bone mineral density of femur bone and lumbar vertebra were measured. A histopathological examination was also carried out. AKBA ameliorated all tested parameters and restored a normal histological structure. Thus, AKBA showed good antiosteoporotic activity, which may be mediated through its suppression of the NF-κB-induced TNF-α signaling pathway.

Evaluation of the effectiveness of pharmacological correction of experimental osteoporosis by glucosamine sulfate, strontium chloride, and their combination

Objective. To study the osteoprotective activity of glucosamine sulfate, strontium chloride, and their combinations on a model of experimental osteoporosis in laboratory animals (OVX model) in comparison with the Strometta preparation and control (OVX without correction). Materials and methods. The material for the study was female Wistar rats weighing 250 ± 30 g. To simulate osteoporosis, bilateral ovariectomy was performed. Microcirculation was evaluated by Doppler flowmetry. Digital X-ray densitometry was used to determine bone density. Using histological morphometry, the transverse size of the trabeculae of the spongy bone tissue was studied. Results. In such parameters as bone density, microcirculation, and the average width of bone trabeculae, significant differences were established compared with the control (OVX without correction) for groups with correction of glucosamine sulfate, strontium chloride, and their combination, and thus their osteoprotective effect was confirmed. Conclusion. In the future, glucosamine sulfate, strontium chloride, and their combination can be used for drug prevention of osteoporosis in the postmenopausal period. However, for the introduction of strontium chloride and its combination with glucosamine sulfate into clinical practice, it is necessary to conduct complete preclinical and clinical trials.