A Study of Serum Bone Alkaline Phosphatase Levels in Rats with Experimental Equivalents of Hypothyroidism and Osteoarthritis on the Background of NSAIDS and Paracetamol Administration
Authors:   State Institution Dnipropetrovsk Medical Academy of the Ministry of Health of Ukraine. 9, Vernadsky St., Dnipro 49044, Ukraine, Nosivets D. S. 
Published: February 2021

The article investigated changes in the level of bone alkaline phosphatase under the influence of non-steroidal anti-inflammatory drugs and paracetamol under experimental equivalents of hypothyroidism and osteoarthritis. There is a clear need to identify biomarkers that could predict a patient's response to osteoarthritis treatment, primarily in comorbid conditions. It is known that hypofunction of the thyroid gland leads to metabolic disorders that negatively affect the condition of bone and cartilage, causing the development of osteoarthritis. One manifestation of osteoarthritis is considered to be a pathological change in the subchondral bone, which responds to the disease by the formation of sclerosis, marginal bone growths and the formation of deformation of the joint surfaces due to the destruction of bone tissue. Although non-steroidal anti-inflammatory drugs are effective in reducing pain and disability in patients with osteoarthritis, it is still unclear to what extent these drugs can affect joint metabolism and, therefore, joint structure, especially against the background of functional thyroid insufficiency. The purpose of the study was to research the pharmacological activity of non-steroidal anti-inflammatory drugs and paracetamol on the level of bone alkaline phosphatase in the serum of rats with experimental equivalents of hypothyroidism and osteoarthritis. Material and methods. The experiments were carried out on 140 white outbred rats of both sexes, which recreated osteoarthritis and hypothyroidism. Experimental osteoarthritis was performed by single intra-articular administration of 0.1 ml of monoacetic acid solution in the knee joint. The solution was prepared at a rate of 3 mg of the reagent on 50 μl of sterile physiological saline. Experimental hypothyroidism was reconstructed by enteral administration of a 0.02% solution of carbimazole prepared at a rate of 5 mg per 250 ml of physiological solution and given with a drinking ration of animals for 6 weeks. The adequacy of the model was confirmed by the level of serum TSH, T3 and T4 in rats. Results and discussion. After the formation of experimental models on the 42nd day of the experiment, the animals were divided into 14 groups and drug administration began daily for 5 days. The quantitative level of bone alkaline phosphatase of blood serum was determined by competitive in vitro ELISA twice on the 42 and 47th days of the experiment. Blood samples were obtained from the rat tail vein by puncture using a vacuum system at 42 and 47th days of the experiment. Statistical data processing was performed using the Statistica 6.1 software package (StatSoftInc., Serial number AGAR909E415822FA) and included calculations of arithmetic mean values (M) and their errors (± m). The probability of the difference between the arithmetic mean (p) values of the indices was made using non-parametric U-criterion Mann-Whitney. The determination of the probability of intragroup and intergroup differences was performed using the Student’s t-test and the method of variance analysis (ANOVA). Differences were considered statistically significant at p≤0.05. Conclusion. The author found out that determining the level of bone alkaline phosphatase allowed evaluating the anti-inflammatory activity non-steroidal anti-inflammatory drugs on the background of experimental equivalents of osteoarthritis and hypothyroidism. The data obtained from rat’s serum bone alkaline phosphatase reflects the extent of the effects of non-steroidal anti-inflammatory drugs and paracetamol due to the interaction of drugs in experimental osteoarthritis and hypothyroidism. According to the degree of influence on degenerative-dystrophic processes in bone tissue the investigated drugs can be arranged as follows: diclofenac sodium > ibuprofen > meloxicam > nimesulide > celecoxib > paracetamol