The use of clozapine is protective for low bone mineral density induced by prolactin-raising antipsychotics in inpatients with schizophrenia



Low bone mineral density (BMD) is common among patients with schizophrenia; however, the pathogenesis is still unclear. Different types of antipsychotics may have different effects on BMD in inpatients with schizophrenia.


This retrospective study aimed to evaluate the effects of prolactin-raising (PR) antipsychotics vs. clozapine combined with PR antipsychotics on BMD of patients with schizophrenia and analyzed clinically related factors that may affect BMD.


A total of 125 participants (males/females = 62/63) were included. Patients were treated with PR antipsychotics vs. clozapine combined with PR antipsychotics. They were similar in demographic and clinical characteristics. BMD was examined in their lumbar spine and proximal femur by a dual-energy X-ray (DEXA) absorption measurement device. Laboratory variables (including blood levels of prolactin, estradiol, testosterone, and cortisol) were collected.


Among 125 inpatients with schizophrenia, the prevalence of osteoporosis and low BMD (including osteoporosis and osteopenia) was 26.4% and 64%. The average BMD T value in patients receiving clozapine combined with PR antipsychotics was significantly higher than in patients receiving PR antipsychotics (p < 0.05). Patients in the clozapine combined with PR antipsychotic group had higher testosterone levels than the PR antipsychotic group (Z = − 2.77, p = 0.006). Linear logistic regression analysis indicated that clozapine combined with PR antipsychotic treatment (p < 0.05) and higher estradiol level (p < 0.05) may be significantly associated with higher BMD.


Our results suggest that the use of clozapine may be a protective factor for low BMD induced by PR antipsychotics in inpatients with schizophrenia. The possible mechanism is that clozapine may protect BMD by regulating estrogen and testosterone levels, but the mechanism by which clozapine regulates these two sex hormones needs further investigation.

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This study was funded by Key Diagnosis and Treatment Program of Suzhou (LCZX201515), Introduction Project of Suzhou Clinical Expert Team (SZYJTD201715), Suzhou Key Medical Center for Psychiatric Diseases (Szzx201509), and Suzhou Science and Technology Project (SS201881).

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Correspondence to Xiangdong Du.

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Qiu, J., Gong, H., Wang, B. et al. The use of clozapine is protective for low bone mineral density induced by prolactin-raising antipsychotics in inpatients with schizophrenia. Arch Osteoporos 15, 98 (2020).

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  • Clozapine
  • Schizophrenia
  • BMD
  • Prolactin-raising antipsychotics