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Long-term second-generation antipsychotics decreases bone formation and resorption in male patients with schizophrenia

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Abstract

Rationale

Patients with schizophrenia with second-generation antipsychotics (SGAs) treatment have shown an increased risk of bone fragility and susceptibility to fracture; however, it is still unclear whether this risk is derived from the effect of antipsychotics on balance of bone metabolism.

Objectives

We investigated the changes of two bone turnover biomarkers (BTMs) concentrations in people with schizophrenia receiving SGAs: procollagen type I aminoterminal propeptide (PINP) and C-terminal telopeptide of type I collagen (CTX-1) as BTMs of osteogenesis and bone resorption, respectively, to explore how antipsychotics contribute to bone fragility.

Methods

We recruited 59 Chinese male patients with schizophrenia (32 drug-naïve first-episode (DNFE) patients and 27 chronic patients) to undergo 8 weeks SGAs treatment. Fasting peripheral blood samples of pre- and posttreatment were collected, plasma levels of PINP and CTX-1 were measured.

Results

The interaction effects of group and time on PINP and CTX-1 concentrations were found (P = .016 and P = .008). There was a significant decrease for both BTMs concentrations of the posttreatment compared to the pretreatment (P<.001 and P = .003). Chronic patients had significantly higher changes of BTMs concentrations compared to DNFE patients (P = .048 and P = .024). There was a positive correlation of the two BTMs of pretreatment with disease course in DNFE group (r = .37, P = .039;r = .38, P = .035) and a negative correlation of PINP of pretreatment with age in the chronic group (r=-.40, P = .039).

Conclusion

Long-term SGAs medication inhibited osteogenesis in a dose- and time-dependent manner and damaged the balance of bone formation and bone resorption.

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Abbreviations

SGA:

Second-Generation Antipsychotic

BMD:

Bone Mineral Density

BTM:

Bone Turnover Biomarker

BMI:

Body Mass Index

CTX-1:

C-terminal telopeptide of type I collagen

PINP:

procollagen type I aminoterminal propeptide

SD:

Standard Deviation

DNFE:

Drug-Naïve First-Episode

HDL:

High-Density Lipoprotein

LDL:

Low-Density Lipoprotein

ALT:

Alanine Aminotransferase

CHO:

Cholesterol

TG:

Triglyceride

GGT:

Gamma-Glutamyl Transferase

AST:

Aspartate Aminotransferase

ANOVAL:

Analysis of variance

ANCOVA:

Analysis of covariance

SBP:

Systolic Blood Pressure

DBP:

Diastolic Blood Pressure

TGF:

Transforming Growth Factor

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Acknowledgements

We thank all the participants for their willingness to participate in the study and the time that they devoted to the study.

Funding

This work was supported by the following grants: the Technology Support Project of Xinjiang (2017E0267), the “Qingmiao” program of Beijing Municipal Hospital Management Center (QML20212003), the 10th Inner Mongolia Autonomous Region ‘Prairie excellence’ Project, Natural Science Foundation of Xinjiang Province (2017D01C245 and 2018D01C228), Tianshan Youth Project-Outstanding Youth Science and Technology Talents of Xinjiang (2017Q007), and Beijing Natural Science Foundation (7152074).

Role of the funder/sponsor statement The funders had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

Access to data and data analysis Dr. Wang had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. Dr Wang and Ms. Li contributed equally to this work.

Author information

Author notes

  1. Fan Wang and Hui Li contributed equally to this work.

Authors and Affiliations

  1. Beijing Hui-Long-Guan Hospital, Peking University, Beijing, 100096, China

    Fan Wang, Yan Wu & Qingtao Bian

  2. Xinjiang Key Laboratory of Neurological Disorder Research, The Second Affiliated Hospital of Xinjiang Medical University, Urumqi, 830063, China

    Fan Wang & Baoyan Guo

  3. Medical Neurobiology Lab, Inner Mongolia Medical University, Huhhot, 010110, China

    Fan Wang & Yimin Kang

  4. Department of Biomedical Engineering, College of Future Technology, Peking University, Beijing, 100871, China

    Hui Li

  5. Department of Orthopedics, Xiangyang No. 1 People’s Hospital Affiliated to Hubei University of Medicine, Xiangyang, 441000, Hubei, China

    Kaijun Yi

  6. Department of Psychiatry, Yale University School of Medicine, New Haven, CT, 06510, USA

    Xingguang Luo

  7. Fenyang College, Shanxi Medical University, Lvliang, 032200, China

    Qi Wu

  8. Department of Psychiatry, Changzhou Peace Hospital, The 102nd Hospital of The Chinese People’s Liberation Army, Changzhou, 213003, China

    Qi Wu & Qinghe Ma

  9. Department of Internal Medicine, The 904th Hospital of The Chinese People’s Liberation Army, Wuxi, 214004, China

    Qinghe Ma

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  1. Fan Wang
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  2. Hui Li
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Contributions

FW designed the study and secured funding for the study. FW and HL led the drafting of the manuscript. HL led the statistical analyses. KY and QB provided clinical guide. YK and YW input the data. YK and BG finished lab test. QW and QM collected the clinical data. All authors approved the final manuscript for submission.

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Correspondence to Fan Wang.

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Wang, F., Li, H., Yi, K. et al. Long-term second-generation antipsychotics decreases bone formation and resorption in male patients with schizophrenia. Psychopharmacology (2024). https://doi.org/10.1007/s00213-024-06592-y

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