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Risperidone, but Not Olanzapine, Decreases Bone Mineral Density in Female Premenopausal Schizophrenia Patients

Daniel Becker, M.D.; Olga Liver, M.D.; Roberto Mester, M.D.; Micha Rapoport, M.D.; Abraham Weizman, M.D.; and Mordechai Weiss, M.D.

Background: The hyperprolactinemia induced by conventional antipsychotics often leads to osteoporosis. The commonly used atypical antipsychotics risperidone and olanzapine vary in their hyperprolactinemic properties. Therefore, we compared hormone profiles and bone properties in female premenopausal schizophrenia patients treated with either risperidone or olanzapine.

Method: In a cross-sectional study, consecutive premenopausal, female, DSM-IV schizophrenia patients who were treated with either risperidone (N = 12) or olanzapine (N = 14) for at least 2 years were included. Dual energy X-ray absorptiometry evaluated bone mineral density, and multisite quantitative ultrasound measured bone speed of sound. In addition, profiles of urinary excretion of deoxypyridinoline and circulating levels of hormones and lipids were assessed.

Results: Serum prolactin levels were higher in the risperidone-treated group as compared with the olanzapine subjects (123 ± 144 and 25.9 ± 25.7, p < .05). Whereas bone mineral density was similar in the treatment groups, bone speed of sound was lower in the risperidone group as compared with the olanzapine-treated group. Expressed as age-adjusted Z score, bone speed of sound at the radius was -0.31 and 0.58, respectively, p < .05, and at the phalanx, -1.41 and 0.04, respectively, p < .05. The bone speed of sound in the risperidone-treated patients inversely correlated with urinary deoxypyridinoline excretion (r = 0.73, p < .05).

Conclusion: Risperidone treatment, as opposed to olanzapine, for female premenopausal schizophrenia results in hyperprolactinemia and clinically relevant decrease in bone mineral density. The calculated relative risk for fragility fracture of women treated with risperidone as compared to those treated with olanzapine is 1.78 when bone speed of sound was measured at the phalanx and 1.23 when measured at the radius.

(J Clin Psychiatry 2003;64:761-766)

Received June 28, 2002; accepted Dec. 30, 2002. From the Ness Ziona Mental Health Center, Ness Ziona (Drs. Becker, Liver, and Mester); the Department of Medicine C (Dr. Rapoport) and the Endocrine Institute (Dr. Weiss), Assaf Harofeh Medical Center, Zerifin; Geha Psychiatric Hospital, Rabin Medical Center, Petah Tikva (Dr. Weizman); and the Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv (Drs. Becker, Mester, Rapoport, Weizman, and Weiss), Israel.

The authors report no financial affiliation or other relationship relevant to the subject matter of this article.

Corresponding author and reprints: Mordechai Weiss, M.D., Endocrine Institute, Assaf Harofeh Medical Center, Zerifin 70300, Israel (e-mail: