Haloperidol-induced experimental osteoporosis and its correction with dimephosphone

Cover Page


Cite item

Full Text

Open Access Open Access
Restricted Access Access granted
Restricted Access Subscription or Fee Access

Abstract

BACKGROUND: There are reports of the negative impact of neuroleptics long-term use on bone metabolism. Dimephosphone is a drug with proven antirachitic effect.

AIM: To study under experimental conditions the effect of haloperidol on the microelement composition of the bone of experimental rats and the possibilities of its correction with dimephosphone.

MATERIAL AND METHODS: Wistar rats were divided into groups (10 animals in each): the first was the control group; the second group consisted of animals that were administered haloperidol; the third group used haloperidol with dimephosphone. Rats of the second and third groups were administered haloperidol intraperitoneally for 90 days, starting with 15 mg/day and reducing the dose to 5 mg/day. Rats of the third group were administered orally a 15% dimephosphone solution at a dose of 208 mg/kg/day. After the animals were withdrawn from the experiment, the lumbar vertebrae were dissected and the teeth were removed. The content of calcium, magnesium, strontium, zinc and copper ions in bone and teeth was determined by atomic absorption spectrophotometry. Statistical processing was performed using the SPSS 13.0 program.

RESULTS: Long-term use of therapeutic doses of haloperidol in the experiment caused a decrease in the content of calcium and zinc ions by 1.5 times, copper — by 1.7 times in the bones of animals, an increase in the concentration of strontium ions by 1.1 times, which indicated the resorptive effect of the neuroleptic. With the combined use of haloperidol and dimephosphone, the content of calcium ions (by 1.2 times), copper (by 1.4 times) and zinc ions (by 1.1 times) significantly increased; the amount of strontium ions decreased (by 1.1 times) only in bone tissue.

CONCLUSION: Dimephosphone reduces the negative effect of long-term haloperidol administration on the microelement composition of rat bones.

Full Text

Restricted Access

About the authors

Roza Ju. Ilyina

Kazan State Medical Academy — branch of the Russian Medical Academy of Continuous Professional Education

Author for correspondence.
Email: ilroza@yandex.ru
ORCID iD: 0000-0001-8534-1282
SPIN-code: 5820-1789

MD, Cand. Sci. (Med.), Assoc. Prof., Depart. of Maxillofacial Surgery and Surgical Stomatology

Russian Federation, Kazan

Lubov R. Muchamedzhanova

Kazan State Medical Academy — branch of the Russian Medical Academy of Continuous Professional Education; Chuvash State University named after I.N. Ulyanov

Email: lr71@bk.ru
ORCID iD: 0000-0003-0752-6497
SPIN-code: 7078-4299

MD, Dr. Sci. (Med.), Prof., Head of Depart., Depart. of Therapeutic, Pediatric Dentistry and Orthodontia; Prof., Depart. of Propaedeutics of Dental Diseases and New Technologies

Russian Federation, Kazan; Cheboksary

Liliya E. Ziganshina

Kazan State Medical University; Russian Medical Academy of Continuous Professional Education; Peoples' Friendship University of Russia named after Patrice Lumumba

Email: lezign@gmail.com
ORCID iD: 0000-0003-1999-0705
SPIN-code: 6061-7223

MD, Dr. Sci. (Med.), Prof., Depart. of Pharmacology; Lead Coord., Knowledge Translation Center, Russian Medical Academy of Continues Professional Education; Prof., Depart. of General and Clinical Pharmacology

Russian Federation, Kazan; Moscow; Moscow

References

  1. Tyler MW, Zaldivar-Diez J, Haggarty SJ. Classics in chemical neuroscience: Haloperidol. ACS Chem Neurosci. 2017;8(3):444–453. doi: 10.1021/acschemneuro.7b00018
  2. Oosthuizen PP, Emsley RA, Maritz JS, Turner JA, Keyter N. Incidence of tardive dyskinesia in first-episode psychosis patients treated with low-dose haloperidol. J Clin Psychiatry. 2003;64(9):1075–1080. doi: 10.4088/jcp.v64n0913
  3. Liu F, Wu Y, Chen J, Zou T, Qin Y, Teng Z, Su Y, Wu R, Huang J. Risk factors for osteoporosis in chronic schizophrenia on long-term treatment with antipsychotics: A cross-sectional study. BMC Psychiatry. 2023;23(1):454–461. doi: 10.1186/s12888-023-04951-1
  4. De Hert M, Detraux J, Stubbs B. Relationship between antipsychotic medication, serum prolactin levels and osteoporosis/osteoporotic fractures in patients with schizophrenia: A critical literature review. Expert Opin Drug Saf. 2016;15(6):809–823. doi: 10.1517/14740338.2016.1167873
  5. Kunimatsu T, Kimura J, Funabashi H, Inoue T, Seki T. The antipsychotics haloperidol and chlorpromazine increase bone metabolism and induce osteopenia in female rats. Regul Toxicol Pharmacol. 2010;58(3):360–368. doi: 10.1016/j.yrtph.2010.08.001
  6. Yokoyama S, Wakamoto S, Tanaka Y, Nakagawa C, Hosomi K, Takada M. Association between antipsychotics and osteoporosis based on real-world data. Ann Pharmacother. 2020;54(10):988–995. doi: 10.1177/1060028020913974
  7. Liang Y, Su YA, Zhao ZG, Gao N, Huang JZ, Tang MQ, Li KQ, Yang FD, Yu X, Si TM. Acute effects of haloperidol, amisulpride, and quetiapine on bone turnover markers in patients with schizophrenia. J Clin Psychopharmacol. 2015;35(5):583–586. doi: 10.1097/JCP.0000000000000379
  8. Vizel' AO, Garaev RS. Novyi aspekt farmakologicheskogo podkhoda k soedineniyam fosfora. Dimefosfon. (New aspect of the pharmacological approach to phosphorus compounds. Dimephosphone.) Kazan: Pechat'-Servis-XXI vek; 2011. 189 р. (In Russ.)
  9. Ziganshina LE, Lepahin VK, Petrov VI, Habriev RU, editors. Bol'shoi meditsinskii spravochnik. (Large reference book of drugs.) Moscow: GEOTAR-Media; 2011. 3344 р. (In Russ.) EDN: QLYWQP
  10. Ziganshina LE, Burnasheva ZA, Valeeva IH. Comparative study of the effectiveness of dimephosphone and xydiphone in steroid osteoporosis in rats. Experimental and clinical pharmacology. 2000;63(6):39–42. (In Russ.) EDN: NKDNDP
  11. Ilyina RYu, Ziganshina LE. Mineral spectrum of the bone tissue of the centers of odontogenous infections at mentally sick patients treated by dimephosphon. Pacific medical journal. 2014;(3):25–28. (In Russ.) EDN: SYDRUH
  12. Saghazadeh A, Mahmoudi M, Shahrokhi S, Mojarrad M, Dastmardi M, Mirbeyk M, Rezaei N. Trace elements in schizophrenia: A systematic review and meta-analysis of 39 studies (N|=| 5151 participants). Nutr Rev. 2020;78(4):278–303. doi: 10.1093/nutrit/nuz059
  13. Chen X, Li Y, Zhang T, Yao Y, Shen C, Xue Y. Association of serum trace elements with schizophrenia and effects of antipsychotic treatment. Biol Trace Elem Res. 2018;181(1);22–30. doi: 10.1007/s12011-017-1039-6
  14. Kołodziejska B, Stępień N, Kolmas J. The influence of strontium on bone tissue metabolism and its application in osteoporosis treatment. Int J Mol Sci. 2021;22(12):6564–6538. doi: 10.3390/ijms22126564
  15. Anchikova LI, Valeeva IH, Studentsova IA. To the mechanism of the effect of domestic medication dimephosphone. Kazan Medical Journal. 2005;86(2):18–22. (In Russ.) EDN: HRTZQZ
  16. Вelaya ZhE, Rozhinskaya LYa. Surrogate markers in assessment of bisphosphonate effectiveness in osteoporosis treatment (bone mineral density, bone turnover markers). Osteoporosis and Bone Diseases. 2023;26(4):20–25. (In Russ.) doi: 10.14341/osteo13166

Supplementary files

Supplementary Files
Action
1. JATS XML

© 2024 Eco-Vector