Top

Journal of Orthopaedic Surgery and Research

Published in:

Open Access 01-12-2021 | Schizophrenia | Research article

Does clozapine really affect bone mineral density? An experimental study

Authors: Bahattin Kerem Aydin, Selim Safali, Memduha Aydin, Umran Egilmez, Hakan Cebeci, Murat Çelik, Ummuhan Abdulrezzak

Published in: Journal of Orthopaedic Surgery and Research | Issue 1/2021

Abstract

Purpose

The aim of this study was to investigate the effect of clozapine use on bone tissue by applying computerized tomography, dual-energy X-ray absorptiometry, and histological and biomechanical analyses in an experimental rat model.

Methods

Sixteen female Wistar Albino rats were included in this study. These animals were divided into two groups: the control group and the clozapine group. The animals in the clozapine group received 10 mg/kg clozapine, and the animals in the control group received tap water by oral gavage daily for 28 days. After sacrification, the femurs of the rats were used for radiologic, histologic, dual-energy X-ray absorptiometry, and biomechanical evaluations.

Results

Although the mean values of the clozapine group were higher in terms of histological, bone mineral density, and biomechanical evaluations, the statistical analyses were not significantly different.

Conclusion

Clozapine use did not affect bone density in the rats. Clozapine can be the preferred treatment for patients with schizophrenia to avoid osteoporosis. It will be necessary to conduct further long-term follow-up and controlled studies in animals and humans to confirm these findings.

McGrath J, Saha S, Welham J, El Saadi O, MacCauley C, Chant D. A systematic review of the incidence of schizophrenia: the distribution of rates and the influence of sex, urbanicity, migrant status and methodology. BMC Med. 2004;2:13. https://doi.org/10.1186/1741-7015-2-13.CrossRefPubMedPubMedCentral

Costa JL, Smith G, Watson M, Lin JM, Callon K, Gamble G, et al. The atypical anti-psychotic clozapine decreases bone mass in rats in vivo. Schizophr Res. 2010;126(1-3):291–7. https://doi.org/10.1016/j.schres.2010.11.024.CrossRefPubMed

Freedman R. Schizophrenia. N Engl J Med. 2003;349(18):1738–49. https://doi.org/10.1056/NEJMra035458.CrossRefPubMed

Correll CU, Rummel-Kluge C, Corves C, Kane JM, Leucht S. Antipsychotic combinations vs monotherapy in schizophrenia: a meta-analysis of randomized controlled trials. Schizophr Bull. 2009;35(2):443–57. https://doi.org/10.1093/schbul/sbn018.CrossRefPubMed

Halbreich U, Rojansky N, Palter S, Hreshchyshyn M, Kreeger J, Bakhai Y, et al. Decreased bone mineral density in medicated psychiatric patients. Psychosom Med. 1995;57:485–91. https://doi.org/10.1097/00006842-199509000-00011.CrossRefPubMed

Howard L, Kirkwood G, Leese M. Risk of hip fracture in patients with a history of schizophrenia. Br J Psychiatry. 2007;190(2):129–34. https://doi.org/10.1192/bjp.bp.106.023671.CrossRefPubMed

Hugenholtz GW, Heerdink ER, van Staa TP, Nolen WA, Egberts AC. Risk of hip/femur fractures in patients using antipsychotics. Bone. 2005;37(6):864–70. https://doi.org/10.1016/j.bone.2005.07.005.CrossRefPubMed

Lin CH, Lin CY, Wang HS, Lane HY. Long-term use of clozapine is protective for bone density in patients with schizophrenia. Sci Rep. 2019;9(1):3895. https://doi.org/10.1038/s41598-019-40691-7.CrossRefPubMedPubMedCentral

Lin CH, Huang KH, Chang YC, Huang YC, Hsu WC, Lin CY, et al. Clozapine protects bone mineral density in female patients with schizophrenia. Int J Neuropsychopharmacol. 2012;15(7):897–906. https://doi.org/10.1017/S1461145711001507.CrossRefPubMed

10.

Lobach AR, Uetrecht J. Clozapine promotes the proliferation of granulocyte progenitors in the bone marrow leading to increased granulopoiesis and neutrophilia in rats. Chem Res Toxicol. 2014;27(7):1109–19. https://doi.org/10.1021/tx500184c.CrossRefPubMed

11.

Chen CY, Lane HY, Lin CH. Effects of antipsychotics on bone mineral density in patients with schizophrenia: gender differences. Clin Psychopharmacol Neurosci. 2016;14(3):238–49. https://doi.org/10.9758/cpn.2016.14.3.238.CrossRefPubMedPubMedCentral

12.

Lee TY, Chung MY, Chung HK, Choi JH, Kim TY, So HS. Bone density in chronic schizophrenia with long-term antipsychotic treatment: preliminary study. Psychiatry Investig. 2010;7(4):278–84. https://doi.org/10.4306/pi.2010.7.4.278.CrossRefPubMedPubMedCentral

13.

O'Keane V. Antipsychotic-induced hyperprolactinaemia, hypogonadism and osteoporosis in the treatment of schizophrenia. J Psychopharmacol. 2008;22(2 Suppl):70–5. https://doi.org/10.1177/0269881107088439.CrossRefPubMed

14.

Schjerning O, Lykkegaard S, Damkier P, Nielsen J. Possible drug-drug interaction between pregabalin and clozapine in patients with schizophrenia: clinical perspectives. Pharmacopsychiatry. 2015;48(1):15–8. https://doi.org/10.1055/s-0034-1390468.CrossRefPubMed

15.

Wang M, Hou R, Jian J, Mi G, Qiu H, Cao B, et al. Effects of antipsychotics on bone mineral density and prolactin levels in patients with schizophrenia: a 12-month prospective study. Hum Psychopharmacol. 2014;29(2):183–9. https://doi.org/10.1002/hup.2387.CrossRefPubMed

16.

Cui J, Liu H, Shao J, Xu DM, Wang Y, Fei Z, et al. Prevalence, risk factors and clinical characteristics of osteoporosis in Chinese inpatients with schizophrenia. Schizophr Res. 2018;195:488–94. https://doi.org/10.1016/j.schres.2017.10.027.CrossRefPubMed

17.

Bilici M, Cakirbay H, Guler M, Tosun M, Ulgen M, Tan U. Classical and atypical neuroleptics, and bone mineral density, in patients with schizophrenia. Int J Neurosci. 2002;112(7):817–28. https://doi.org/10.1080/00207450290025833.CrossRefPubMed

Title: Does clozapine really affect bone mineral density? An experimental study
Authors: Bahattin Kerem Aydin
Selim Safali
Memduha Aydin
Umran Egilmez
Hakan Cebeci
Murat Çelik
Ummuhan Abdulrezzak
Publication date: 01-12-2021
Publisher: BioMed Central
Keywords: Schizophrenia
Antipsychotics
Osteoporosis
Osteoporosis
Antipsychotics
Clozapine
Haloperidol
Dexamethasone
Published in: Journal of Orthopaedic Surgery and Research / Issue 1/2021
Electronic ISSN: 1749-799X
DOI: https://doi.org/10.1186/s13018-021-02695-w

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Does clozapine really affect bone mineral density? An experimental study

Abstract

Purpose

Methods

Results

Conclusion

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Purpose

Methods

Results

Conclusion

Please log in to get access to this content

Other articles of this Issue 1/2021

The effect of common variants in GDF5 gene on the susceptibility to chronic postsurgical pain

Association between serum estradiol level, sex hormone binding globulin level, and bone mineral density in middle-aged postmenopausal women

Insufficient blood supply of fovea capitis femoris, a risk factor of femoral head osteonecrosis

Curculigoside promotes osteogenic differentiation of ADSCs to prevent ovariectomized-induced osteoporosis

The effect of self-reported knee instability on plantar pressure and postural sways in women with knee osteoarthritis

Comparative efficacy and safety profile for the treatment of humeral bone cysts in children: curettage and mixed bone grafting either with or without elastic intramedullary nailing