Long-term Use of Clozapine is Protective for Bone Density in Patients with Schizophrenia

Low bone mineral density (BMD) prevails among patients with schizophrenia. Antipsychotics use plays an important role in BMD. Previous cross-section study suggests that clozapine treatment may benefit BMD of women with schizophrenia. However, the effect of long-term clozapine therapy on BMD remains unknown. This prospective study compared clozapine and non-clozapine antipsychotics in long-term effects on BMD among both men and women with schizophrenia. Patients with schizophrenia and age-matched healthy individuals were enrolled from two centers. All patients, including clozapine receivers and non-clozapine antipsychotics recipients, kept clinically stable with unchanged antipsychotics and doses for at least 6 months at enrollment and during the follow-up period. BMD was examined by dual-energy X-ray absorptiometer upon enrollment and at 1- or 3-year follow-up. Thorough clinical and laboratory variables were measured too. The mean BMD of patients receiving clozapine was higher than that of the non-clozapine patients at both enrollment and follow-up. Overall, the patients in the clozapine group gained BMD, while those in the non-clozapine group lost BMD after 1-3 years (p = 0.015). There was no significant difference of BMD change between clozapine-treated patients and healthy controls. Factors associated with BMD change in the clozapine group included calcium level (B = -0.607, p = 0.021) and T3 level (B = -0.077, p = 0.007). This longitudinal study suggests that long-term clozapine treatment may protect BMD compared to prolactin-raising and non-clozapine prolactin-sparing antipsychotics among patients with schizophrenia. Future prospective studies are warranted to testify whether switching from non-clozapine antipsychotics to clozapine can rescue BMD.