Advances in Clinical and Experimental Medicine

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Advances in Clinical and Experimental Medicine

2019, vol. 28, nr 6, June, p. 771–776

doi: 10.17219/acem/93729

Publication type: original article

Language: English

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Creative Commons BY-NC-ND 3.0 Open Access

Long-term administration of fenspiride has no negative impact on bone mineral density and bone turnover in young growing rats

Agnieszka Matuszewska1,A,B,C,D,E,F, Beata Nowak1,A,B,C,D,E,F, Diana Jędrzejuk2,B,C, Marcin Landwójtowicz2,B,C, Marek Bolanowski2,C,E, Wojciech Dziewiszek1,B, Anna Merwid-Ląd1,D,E, Ewa Szeląg3,B,C, Krzysztof Zduniak4,B,C, Joanna Kwiatkowska1,B,C, Adam Szeląg1,A,E,F

1 Department of Pharmacology, Wroclaw Medical University, Poland

2 Department of Endocrinology, Diabetology and Isotope Therapy, Wroclaw Medical University, Poland

3 Department of Maxillofacial Orthopedics and Orthodontics, Wroclaw Medical University, Poland

4 Department of Pathomorphology, Wroclaw Medical University, Poland

Abstract

Background. Fenspiride is an antagonist of H1-histamine receptors that is used to treat acute and chronic respiratory tract infections and otitis media in children and adolescents.
Objectives. The aim of the study was to assess the influence of long-term administration of fenspiride on bone mineral density (BMD) and bone turnover in young growing rats.
Material and Methods. The experiment was carried out on 18 young (8-week-old) male Wistar rats receiving either fenspiride 15 mg/kg intragastrically (ig) (group F) or saline solution 4 mL/kg ig (group C) for 3 months. On days 1 and 93, blood samples were collected and serum levels of calcium, phosphorus and markers of bone turnover were measured. On days 2 and 92, BMD was measured with dual-energy x-ray absorptiometry (DXA) using small animal software.
Results. We detected no influence of fenspiride on weight gain, total body BMD (0.212 ±0.010 g/cm2 vs 0.204 ±0.024 g/cm2), hind limb BMD (0.264 ±0.016 g/cm2 vs 0.252 ±0.027 g/cm2), or bone macroscopic parameters. There were no significant differences between group F and group C in serum levels of osteocalcin (group F: 0.42 ±0.09 ng/mL vs group C: 0.43 ±0.08 ng/mL), C-terminal telopeptide of type I collagen (F: 0.31 ±0.08 ng/mL vs C: 0.29 ±0.08 ng/mL), osteoprotegerin (F: 5.47 ±0.78 pg/mL vs C: 5.35 ±1.65 pg/mL), receptor activator of nuclear factor kappa B ligand (F: 0.65 ±0.85 pg/mL vs C: 0.56 ±0.86 pg/mL), parathormone (F: 237 ±182 pg/mL vs C: 289 ±200 pg/mL), total calcium (F: 6.38 ±1.50 mg/dL vs C: 6.83 ±1.71 mg/dL), or inorganic phosphorus (F: 5.19 ±1.76 mg/dL vs C: 5.50 ±1.32 mg/dL).
Conclusion. Long-term administration of fenspiride has no negative impact on BMD and bone metabolism in young growing rats.

Key words

rats, histamine, bone mineral density, bone, fenspiride

References (34)

  1. Kanis JA. Osteoporosis III: Diagnosis of osteoporosis and assessment of fracture risk. Lancet. 2002;359(9321):1929–1936. doi:10.1016/S0140-6736(02)08761-5
  2. Hernlund E, Svedbom A, Ivergård M, et al. Osteoporosis in the European Union: Medical management, epidemiology and economic burden. Arch Osteoporos. 2013;8(1–2):136. doi:10.1007/s11657-013-0136-1
  3. Ferrari S, Bianchi ML, Eisman JA, et al. Osteoporosis in young adults: Pathophysiology, diagnosis, and management. Osteoporos Int. 2012;23(12):2735–2748. doi:10.1007/s00198-012-2030-x
  4. Rizzoli R, Bianchi ML, Garabédian M, McKay HA, Moreno LA. Maximizing bone mineral mass gain during growth for the prevention of fractures in the adolescents and the elderly. Bone. 2010;46(2):294–305. doi:10.1016/j.bone.2009.10.005
  5. Heaney RP, Abrams S, Dawson-Hughes B, et al. Peak bone mass. Osteoporos Int. 2000;11(11):985–1009. doi:10.1007/s001980070020
  6. Viswanathan A, Sylvester FA. Chronic pediatric inflammatory diseases: Effects on bone. Rev Endocr Metab Disord. 2008;9(2):107–122. doi:10.1007/s11154-007-9070-0
  7. Zhang Y, Zheng YX, Zhu JM, Zhang JM, Zheng Z. Effects of antiepileptic drugs on bone mineral density and bone metabolism in children: A meta-analysis. J Zhejiang Univ Sci B. 2015;16(7):611–621. doi:10.1631/jzus.B1500021
  8. Shmelev EI, Kunicina YL. Comparison of fenspiride with beclomethasone as adjunctive anti-inflammatory treatment in patients with chronic obstructive pulmonary disease. Clin Drug Investig. 2006;26(3):151–159.
  9. Volkova LI, Budkova AA, Filonova NN, et al. Efficacy of a complementary anti-inflammatory treatment with erespal in chronic obstructive and nonobstructive bronchitis. Ter Arkh. 2004.
  10. Khawaja AM, Liu YC, Rogers DF. Effect of fenspiride, a non-steroidal anti-inflammatory agent, on neurogenic mucus secretion in ferret trachea in vitro. Pulm Pharmacol Ther. 1999;12(6):363–368. doi:10.1006/pupt.1999.0221
  11. Aasarod KM, Stunes AK, Mosti MP, et al. Effects of the histamine 1 receptor antagonist cetirizine on the osteoporotic phenotype in H+/K+ ATPase beta subunit KO mice. J Cell Biochem. 2016;117(9):2089–2096. doi:10.1002/jcb.25514
  12. Blackwell KA, Raisz LG, Pilbeam CC. Prostaglandins in bone: Bad cop, good cop? Trends Endocrinol Metab. 2010;21(5):294–301. doi:10.1016/j.tem.2009.12.004
  13. Hikiji H, Takato T, Shimizu T, Ishii S. The roles of prostanoids, leukotrienes, and platelet-activating factor in bone metabolism and disease. Prog Lipid Res. 2008;47(2):107–126. doi:10.1016/j.plipres.2007.12.003
  14. Folwarczna J, Janas A, Pytlik M, Śliwiński L, Wiercigroch M, Brzęczek A. Modifications of histamine receptor signaling affect bone mechanical properties in rats. Pharmacol Reports. 2014;66(1):93–99. doi:10.1016/j.pharep.2013.08.010
  15. Ezzat BA, Abbass MMS. The ability of H1 or H2 receptor antagonists or their combination in counteracting the glucocorticoid-induced alveolar bone loss in rats. J Oral Pathol Med. 2014;43(2):148–156. doi:10.1111/jop.12104
  16. Kuzubova NA, Lebedeva ES, Fedin AN, Dvorakovskaya IV, Preobrazhenskaya TN, Titova ON. Effect of fenspiride on bronchial smooth muscle of rats with chronic obstructive pulmonary disease. J Smooth Muscle Res. 2013;49:46–54. doi:10.1540/jsmr.49.46
  17. Cataldi M, Borriello F, Granata F, Annunziato L, Marone G. Histamine receptors and antihistamines: From discovery to clinical applications. Chem Immunol Allergy. 2014;100:214–226. doi:10.1159/000358740
  18. Fitzsimons R, van der Poel L-A, Thornhill W, du Toit G, Shah N, Brough HA. Antihistamine use in children. Arch Dis Child Educ Pract Ed. 2015;100(3):122–131. doi:10.1136/archdischild-2013-304446
  19. De Benedictis FM, De Benedictis D, Canonica GW. New oral H1 antihistamines in children: Facts and unmet needs. Allergy Eur J Allergy Clin Immunol. 2008;63(10):1395–1404. doi:10.1111/j.1398-9995.2008.01771.x
  20. Barete S, Assous N, de Gennes C, et al. Systemic mastocytosis and bone involvement in a cohort of 75 patients. Ann Rheum Dis. 2010;69(10):1838–1841. doi:10.1136/ard.2009.124511
  21. Biosse-Duplan M, Baroukh B, Dy M, de Vernejoul M-C, Saffar J-L. Histamine promotes osteoclastogenesis through the differential expression of histamine receptors on osteoclasts and osteoblasts. Am J Pathol. 2009;174(4):1426–1434. doi:10.2353/ajpath.2009.080871
  22. Deyama Y, Kikuiri T, Ohnishi GI, et al. Histamine stimulates production of osteoclast differentiation factor/receptor activator of nuclear factor-kappaB ligand by osteoblasts. Biochem Biophys Res Commun. 2002;298(2):240–246. doi:10.1016/S0006-291X(02)02440-3
  23. Neumann E, Müller-Ladner U, Frommer KW. Entzündung und Knochenmetabolismus. Z Rheumatol. 2014;73(4):342–348. doi:10.1007/s00393-013-1288-5
  24. Lelovas PP, Xanthos TT, Thorma SE, Lyritis GP, Dontas IA. The laboratory rat as an animal model for osteoporosis research. Comp Med. 2008;58(5):424–430.
  25. Tauer JT, Hofbauer LC, Jung R, et al. Impact of long-term exposure to the tyrosine kinase inhibitor imatinib on the skeleton of growing rats. PLoS One. 2015;10(6):e0131192. doi:10.1371/journal.pone.0131192
  26. Lin S, Huang J, Zheng L, et al. Glucocorticoid-induced osteoporosis in growing rats. Calcif Tissue Int. 2014;95(4):362–373. doi:10.1007/s00223-014-9899-7
  27. Ferencz V, Meszaros S, Csupor E, et al. Increased bone fracture prevalence in postmenopausal women suffering from pollen-allergy. Osteoporos Int. 2006;17(3):484–491. doi:10.1007/s00198-005-0011-z
  28. Ikawa Y, Yonekawa T, Ohkuni Y, Kuribayashi M, Fukino K, Ueno K. A comparative study of histamine activities on differentiation of osteoblasts and osteoclasts. J Toxicol Sci. 2007;32(5):555–564. doi:10.2131/jts.32.555
  29. Rico H, Gómez M, Revilla M, et al. Effects of promethazine on bone mass and on bone remodeling in ovariectomized rats: A morphometric, densitometric, and histomorphometric experimental study. Calcif Tissue Int. 1999;65(4):272–275. doi:10.1007/s002239900697
  30. Kinjo M, Setoguchi S, Solomon DH. Antihistamine therapy and bone mineral density: Analysis in a population-based US sample. Am J Med. 2008;121(12):1085–1091. doi:10.1016/j.amjmed.2008.06.036
  31. Meh A, Sprogar Š, Vaupotic T, et al. Effect of cetirizine, a histamine (H1) receptor antagonist, on bone modeling during orthodontic tooth movement in rats. Am J Orthod Dentofac Orthop. 2011;139(4):e323–329. doi:10.1016/j.ajodo.2009.11.013
  32. Gatti D, Senna G, Viapiana O, Rossini M, Passalacqua G, Adami S. Allergy and the bone: Unexpected relationships. Ann Allergy Asthma Immunol. 2011;107(3):202–206. doi:10.1016/j.anai.2011.03.018
  33. Akino K, Mineda T, Mori N, Hirano A, Imaizumi T, Akita S. Attenuation of cysteinyl leukotrienes induces human mesenchymal stem cell differenti-ation. Wound Repair Regen. 2006;14(3):343–349. doi:10.1111/j.1743-6109.2006.00130.x
  34. Wixted JJ, Fanning PJ, Gaur T, et al. Enhanced fracture repair by leukotriene antagonism is characterized by increased chondrocyte proliferation and early bone formation: A novel role of the cysteinyl IL-1 receptor. J Cell Physiol. 2009;221(1):31–39. doi:10.1002/jcp.21809