ISSN 2415-3060 (print), ISSN 2522-4972 (online)
  • 9 of 60
JMBS 2019, 4(6): 67–73
Experimental Medicine and Morphology

Influence of Non–Steroidal Anti–Inflammatory Drugs on the Level CTX II Marker under Experimental Hypothyroidism and Osteoarthritis

Nosivets D. S.

Thyroid diseases are an urgent problem in modern society due to the wide spread of this pathology and related disorders of the musculoskeletal system, however, the issue of the influence and interaction of NSAIDs in the treatment of osteoarthritis against hypothyroidism has not been studied enough. The purpose of the study was to investigate the level of CTX II marker under the influence of NSAIDs under experimental equivalents of hypothyroidism and osteoarthritis. Material and methods. Experimental osteoarthritis was reproduced through a single intra–articular administration of 0.1 ml of monoiodoacetate acid solution into the knee joint, which was prepared at the rate of 3 mg of reagent to 50 µl of sterile saline. Experimental hypothyroidism was reproduced by enteral introduction of a 0.02% solution of carbimazole (the drug "Espa–carb", manufactured by Esparma GmbH, Germany; in tablets of 5 or 10 mg), which was prepared at the rate of 5 mg in 250 ml saline and given with drinking diet for 6 weeks. The drugs were administered daily from day 42 of the experiment on the background of increasing pathological changes within 5 days. To obtain a homogeneous suspension for intragastric administration tablets used solution Tween–80 (Polysorbate 80, Ukraine). The quantitative level of CTX II serum was determined by competitive ELISA in vitro twice (for 42 and 47 days of the experiment) using the enzyme immunoassay system "RatCartiLaps®" (Cobas, Roche Diagnostics, Switzerland) according to the method of the manufacturer. Results and discussion. The author established that obtained changes in the level of CTX II marker in the serum of rats under the influence of NSAIDs and paracetamol occurred unequally. Thus, on the 42nd day there was a marked increase in the level of CTX II marker in all experimental groups, reflecting the development of pathological changes under the influence of experimental models, which increased slightly by the 47th day in the experiment in group I. Under the influence of basic substitution therapy with L–thyroxine, there was a slight tendency to decrease the test marker, which was reflected by the indicators of experimental group II. Conclusion. The study results showed that the definition of level CTX II marker allows to assess the level of degenerative changes in the cartilage on the background of experimental equivalents of osteoarthritis and hypothyroidism. The degree of impact on degenerative processes in the cartilage tissue of the investigated drugs can be arranged as follows: nimesulide > celecoxib > meloxicam > ibuprofen > diclofenac sodium > paracetamol. The obtained data of the level CTX II serum of rats reflected the degree of influence of NSAIDs and paracetamol on the disintegration of collagen type II by interaction of the drugs in experimental osteoarthritis and hypothyroidism.

Keywords: hypothyroidism, osteoarthritis, non–steroidal anti–inflammatory drugs, basic pharmacotherapy, biochemical markers, CTX II

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  1. Nosivets DS. Vliyanie funktsionalnoy nedostatochnosti shchitovidnoy zhelezy na kostno–khryashchevuyu tkan [Influence of functional insufficiency of the thyroid gland on bone and cartilage tissue]. Morfologiya. 2019; 1(13): 47–51. [Russian]
  2. Williams GR.Thyroid hormone actions in cartilage and bone. Eur Thyroid J. 2013; 2(1): 3–13.
  3. Ehmouda F, Eljazwi E, Eldrasi N. Effect of L thyroxine therapy on musculoskeletal symptoms of hypothyroidism. Lecture in faculty medicine in Benghazi University. Pan Arab Rheumatology. 2014; 2014: 1–16.
  4. Panikar VI, Pavlova IA, Zhernakova NI, Shcherban EA. Osteoartroz i osteoporoz kak komponenty polimorbidnoy geriatricheskoy patologii [Osteoarthrosis and osteoporosis as components of polymorbid geriatric pathology]. Sovremennye problemy nauki i obrazovaniya. 2018, 4. [Russian]
  5. Zhang R–X, Ren K, Dubner R. Osteoarthritis pain mechanisms: Basic studies in animal models. Osteoarthritis Cartilage. 2013; 21(9): 1308–15.
  6. Mobasheri A, Bay–Jensen AC, Spil WE, Larkin J, Levesque MC. Osteoarthritis year in review 2016: biomarkers (biochemical markers). Osteoarthritis and Cartilage. 2017; 25(2): 199–208.
  7. Nosivets DS. Vliyanie kombinatsii NPVS na techenie osteoartroza pri soputstvuyushchem gipotireoze. Problemy endokrinnoy patologii. 2019; 2(68): 40–5. [Russian]
  8. Voloshina LO, Voloshin OI, Pashkovska NV. Osoblivosti kompleksnogo likuvannya khvorikh na osteoartroz na tli subklshichnogo gipotireozu [Features of complex treatment of patients with osteoarthritis on the background of subclinical hypothyroidism]. Mat nauk–prakt konf «Aktualni pitannya zberezhennya zdorov’ya lyudini». Uzhgorod, 2014. 2014: 48–51. [Ukrainian]
  9. Guingamp C, Gegout–Pottie P, Philippe L, Terlain B, Netter P, Gillet P. Mono–iodoacetate–induced experimental osteoarthritis: a dose–response study of loss of mobility, morphology, and biochemistry. Arthritis Rheum. 1997; 40(9): 1670–9.
  10. Nosivets DS. Eksperimentalnye modeli patologii khryashchevoy tkani [Experimental models of cartilage pathology]. Zaporozhskiy meditsinskiy zhurnal. 2019; 4(115): 554–60. [Russian]
  11. Argumedo GS, Sanz CR, Olguín HJ. Experimental models of developmental hypothyroidism. Horm Metab Res. 2012; 44(2): 79–85.–0031–1297941
  12. Kostyuk VO. Prikladna statistika [Applied statistics]: navch posibnik. Kh: KhNUMG im OM Beketova; 2015. 191 p. [Ukrainian]
  13. Davies PH, Franklyn JA. The effects of drugs on tests of thyroid function. Eur J Clin Pharmacol. 1991; 40(5): 439–51.
  14. Wenzel KW. Disturbances of thyroid function tests by drugs. Acta Med Austriaca. 1996; 23(1–2): 57–60.
  15. Bishnoi A, Carlson HE, Gruber BL, Kaufman LD, Bock JL, Lidonnici K. Effects of commonly prescribed nonsteroidal anti–inflammatory drugs on thyroid hormone measurements. Am J Med. 1994; 96: 235–8.–9343(94)90148–1
  16. Daminet S, Ferguson DC. Influence of drugs on thyroid function in dogs. J Vet Intern Med. 2003; 17(4): 463–72.–1676.2003.tb02467.x
  17. McConnell RJ. Changes in thyroid function tests during shortterm salsalate use. Metabolism. 1999; 48(4): 501–3.–0495(99)90111–7
  18. Larsen PR. Salicylate–induced increases in free triiodothyronine in human serum: Evidence of inhibition of triiodothyronine binding to thyroxine–binding globulin and thyroxine–binding prealbumin. J Clin Invest. 1972; 51(5): 1125–34.
  19. McConnell RJ. Abnormal thyroid function test results in patients taking salsalate. J Am Med Assoc. 1992; 267(9): 1242–3.
  20. Carlson HE, Kael AT, Schulman PE, Tan M, Bock JL. Effects of several nonsteroidal anti–inflammatory drugs on thyroid function tests. J Rheumatol. 1999; 26(8): 1855–6.
  21. Samuels MH, Pillote K, Asher D, Nelson JC. Variable effects of nonsteroidal antiinflammatory agents on thyroid test results. J Clin Endocrinol Metab. 2003; 88(12): 5710–6.–021869
  22. Löfvall H, Katri A, Dąbrowska A, Karsdal MA. GPDPLQ1237–A type II collagen neo–epitope biomarker of osteoclast– and inflammation–derived cartilage degradation in vitro. Scientific Reports. 2019; 9(1): 3050.–019–39803–0
  23. Wang XZ, Gao NY, Liu T, Shen J, Wei SP, Zheng YX, et al. Application of biomarker CTX– II in osteoarthritis. Zhongguo Gu Shang. 2013;26(3): 260–3.
  24. Kraus VB, Burnett B, Coindreau J, Cottrell S, Eyre D, Gendreau M, et al. Application of biomarkers in the development of drugs intended for the treatment of osteoarthritis. Osteoarthritis and Cartilage. 2011; 19(5): 515–42.
  25. Ma T, Li Y, Wang G, Li X, Jiang RL, Song XP, et al. Changes in synovial fluid biomarkers after experimental equine osteoarthritis. Vet Res. 2017; 61(4): 503–8.–2017–0056
  26. Bai B, Li Y. Combined detection of serum CTX–II and COMP concentrations in osteoarthritis model rabbits: an effective technique for early diagnosis and estimation of disease severity. J Orthopaedic Surgery and Research. 2016; 11(1): 149.–016–0483–x
  27. Lorenz H, Wenz W, Ivancic M, Steck E. Richter W. Early and stable upregulation of collagen type II, collagen type I and YKL40 expression levels in cartilage during early experimental osteoarthritis occurs independent of joint location and histological grading. Arthritis Res Ther. 2005; 7: 156–65.
  28. Bai L, Wang Y, Ba G. Research progress of C terminal propeptide of collagen type II. Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi. 2011; 25(1): 66–9.
  29. van Spil WE, Jansen NW, Bijlsma JW, Reijman M, DeGroot J, Welsing PM, et al. Clusters within a wide spectrum of biochemical markers for osteoarthritis: data from CHECK, a large cohort of individuals with very early symptomatic osteoarthritis. Osteoarthritis Cartilage. 2012; 20(7): 745–54.
  30. Klerk B, Lafeber FP, van Spil WE. Associations of CTX–II with biochemical markers of bone turnover raise questions about its tissue origin: new insights from CHECK. Ann Rheum Dis. 2014; 73(7): 39.–2014–205494
  31. Karsdal MA, Byrjalsen I, Bay–Jensen AC, Henriksen K, Riis BJ, Christiansen C. Biochemical markers identify influences on bone and cartilage degradation in osteoarthritis – the effect of sex, Kellgren–Lawrence (KL) score, Body Mass Index (BMI), oral salmon calcitonin (sCT) treatment and diurnal variation. BMC Musculoskeletal Disorders. 2010; 11: 125.–2474–11–125
  32. Xin L, Wu Z, Qu Q, Wang R, Tang J, Chen L. Comparative study of CTX–II, Zn2+, and Ca2+ from the urine for knee osteoarthritis patients and healthy individuals. Medicine. 2017; 96: 32.
  33. Sarukawa J, Takahashi M, Doi M, Suzuki D, Nagano A. A longitudinal analysis of urinary biochemical markers and bone mineral density in str/ort mice as a model of spontaneous osteoarthritis. Arthritis Rheum. 2010; 62(2): 463–71.
  34. Saberi Hosnijeh F, Siebuhr AS, Uitterlinden AG, Oei EH, Hofman A, Karsdal MA, Saberi Hosnijeh F, Siebuhr AS, Uitterlinden AG, Oei EH, Hofman A, Karsdal MA,et al. Association between biomarkers of tissue inflammation and progression of osteoarthritis: evidence from the Rotterdam study cohort. Arthritis Research & Therapy. 2016; 18: 81.–016–0976–3
  35. Arends RH, Karsdal MA, Verburg KM, Bay–Jensen AC. Biomarkers associated with rapid cartilage loss and bone destruction in osteoarthritis patients. Osteoarthritis and Cartilage. 2016; 24: 8–62.
  36. Li ZN, Wei XC. Diagnosis value of biological markers CTX–II in osteoarthritis. Zhongguo Gu Shang. 2008; 21(9): 719–22.
  37. Song Y, Guan J, Wang H, Ma W, Li F, Xu F, et al. Possible involvement of serum and synovial fluid resistin in knee osteoarthritis: cartilage damage, clinical, and radiological links. J Clinical Laboratory Analysis. 2016; 30(5): 437–43.
  38. Kumm J, Tamm A, Lintrop M, Tamm A. The value of cartilage biomarkers in progressive knee osteoarthritis: cross–sectional and 6–year follow–up study in middle–aged subjects. Rheumatol Int. 2013; 33(4): 903–11.–012–2463–8
  39. Oestergaard S, Chouinard L, Doyle N, Karsdal MA, Smith SY, Qvist P, et al. The utility of measuring C–terminal telopeptides of collagen type II (CTX–II) in serum and synovial fluid samples for estimation of articular cartilage status in experimental models of destructive joint diseases. Osteoаrthritis and Cartilage. 2006; 14(7): 670–9.
  40. Garnero P, Ayral X, Rousseau J–C, Christgau S, Sandell LJ, Dougados M, et al. Uncoupling of type II collagen synthesis and degradation predicts progression of joint damage in patients with knee osteoarthritis. Arthritis Rheum. 2002; 46(10): 2613–24.
  41. Watari T, Naito K, Sakamoto K, Kurosawa H, Nagaoka I, Kaneko K. Evaluation of the effect of oxidative stress on articular cartilage in spontaneously osteoarthritic STR/OrtCrlj mice by measuring the biomarkers for oxidative stress and type II collagen degradation/synthesis. Experimental and Therapeutic Medicine. 2011; 2(2): 245–50.
  42. Yarmola EG, Shah YY, Kloefkorn HE, Dobson J, Allen KD. Comparing intra–articular CTXII levels assessed via magnetic capture or lavage in a rat knee osteoarthritis model. Osteoarthritis Cartilage. 2017; 25(7): 1189–94.
  43. Deveza LA, Kraus VB, Collins JE, Guermazi A, Roemer FW, Bowes M, et al. The association between biochemical markers of bone turnover and bone changes on imaging – data from the osteoarthritis initiative. Arthritis Care Res (Hoboken). 2017; 69(8): 1179–91.
  44. Isaka S, Someya A, Nakamura S, Naito K, Nozawa M, Inoue N, et al. Evaluation of the effect of oral administration of collagen peptides on an experimental rat osteoarthritis model. Experimental and therapeutic medicine. 2017; 13: 2699–706.
  45. Di Cesare Mannelli L, Micheli L, Zanardelli M, Ghelardini C. Low dose native type II collagen prevents pain in a rat osteoarthritis model. BMC Musculoskeletal Disorders. 2013; 14: 228.–2474–14–228
  46. Nielsen RH, Bay–Jensen AC, Byrjalsen I, Karsdal MA. Oral salmon calcitonin reduces cartilage and bone pathology in an osteoarthritis rat model with increased subchondral bone turnover. Osteoarthritis and Cartilage. 2011; 19(4): 466–73.