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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\u20133 years (p\u2009=\u20090.015). 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\u2009=\u2009\u22120.607, <jats:italic>p<\/jats:italic>\u2009=\u20090.021) and T3 level (B\u2009=\u2009\u22120.077, <jats:italic>p<\/jats:italic>\u2009=\u20090.007). 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.<\/jats:p>","DOI":"10.1038\/s41598-019-40691-7","type":"journal-article","created":{"date-parts":[[2019,3,7]],"date-time":"2019-03-07T11:03:04Z","timestamp":1551956584000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Long-term Use of Clozapine is Protective for Bone Density in Patients with Schizophrenia"],"prefix":"10.1038","volume":"9","author":[{"given":"Chieh-Hsin","family":"Lin","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chun-Yuan","family":"Lin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong-Song","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hsien-Yuan","family":"Lane","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2019,3,7]]},"reference":[{"key":"40691_CR1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2474-10-1","volume":"10","author":"JH Renn","year":"2009","unstructured":"Renn, J. 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