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Antipsychotics and bones

Vol. 8, No. 9 / September 2009

Antipsychotics were not mentioned in Drs. Sarah K. Rivelli and Andrew J. Muzyk’s list of psychiatric medications that could increase the risk of osteoporosis (“Protect patients’ bones when prescribing,” Medicine in Brief, Current Psychiatry, June 2009). Data show that hyperprolactinemia associated with antipsychotics can increase osteoporosis risk.1

Antipsychotics often are given on a long-term basis, which creates concern for all patients taking these medications, especially because obtaining prolactin levels typically is not the standard of care. For medical professionals, linking hyperprolactinemia with osteoporosis may seem like common sense, as is linking hyperprolactinemia with antipsychotics, but we rarely correlate antipsychotics with osteoporosis. We should make that connection in consideration of the long-term health effects antipsychotics have on our patients.

James Cho, MD
Forensic psychiatry fellow
University of Cincinnati
Cincinnati, OH


1. Meaney AM, Smith S, Howes OD, et al. Effects of long-term prolactin-raising antipsychotic medication on bone mineral density in patients with schizophrenia. Br J Psychiatry. 2004;184:503-508.

Drs. Rivelli and Muzyk respond

We agree with Dr. Cho about the need to be aware of deleterious effects of antipsychotics on bone density. Hyperprolactinemia from antipsychotics results from antagonism of D2 receptors on pituitary lactotroph cells. Blockade prevents dopamine stimulation, which normally inhibits prolactin release. Stimulation of serotonin-2A (5-HT2A) receptors on pituitary lactotroph cells also contributes to prolactin release. Second-generation antipsychotics (SGAs) strongly inhibit 5-HT2A receptors in the tuberoinfundibular pathway, which means these agents may have a lower risk of hyperprolactinemia compared with first-generation antipsychotics (FGAs). Osteoporosis is caused by prolonged dysregulation of the HPA axis and hypogonadism.1

Other factors—including a schizophrenia diagnosis, sedentary lifestyle, smoking, substance abuse, and malnutrition—also may contribute to osteoporosis.2 This condition may be highly prevalent and underdiagnosed in male schizophrenics.3 We would consider patients on chronic antipsychotic therapy—particularly those receiving higher doses or FGAs—at higher risk of osteoporosis.

Sarah K. Rivelli, MD
Associate program director, internal medicine-psychiatry residency

Andrew J. Muzyk, PharmD
Clinical pharmacist
Duke University Medical Center
Durham, NC


1. Byerly M, Suppes T, Tran QV, et al. Clinical implications of antipsychotic-induced hyperprolactinemia in patients with schizophrenia spectrum or bipolar spectrum disorder. J Clin Psychopharmacol. 2007;27(6):639-661.

2. Halbreich U. Osteoporosis, schizophrenia and antipsychotics: the need for a comprehensive multifactorial evaluation. CNS Drugs. 2007;21(8):641-657.

3. Meyer JM, Lehman D. Bone mineral density in male schizophrenia patients: a review. Ann Clin Psychiatry. 2006;18(10):43-48.

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