Antipsychotic drugs - A new risk factor for osteoporosis in young women with schizophrenia?
Schizophrenic illness is associated with high rates of osteoporosis, the etiology of which remains obscure, but which may be at least partly explained by the prolactin-raising properties of antipsychotic medication. Conventional antipsychotics all cause hyperprolactinemia, whereas a limited number of atypical antipsychotic drugs do not. To investigate this further, we designed a cross-sectional comparison study between groups taking either prolactin-raising or prolactin-sparing antipsychotic medication. Participants were required to be premenopausal women with a diagnosis of schizophrenia, and to have received exclusively either prolactin-raising (n = 26), or olanzapine (n = 12) antipsychotic medication. Half of the subjects in the prolactin-raising group were being treated with conventional (n = 13), and half with newer "atypical," antipsychotic drugs (n = 13). Subjects had lumbar spine and hip bone mineral density (BMD) evaluated by a dual-energy x-ray absorptiometer (DEXA) scan. A blood sample was taken to measure prolactin and sex hormone axis measures. The results demonstrated that the group taking prolactin-raising medication had higher rates of bone pathology, compared with the olanzapine group. High prolactin levels were related to measures of hypogonadism and low BMD values. Within the prolactin-raising group, those taking newer atypical compounds had higher levels of prolactin, lower levels of sex hormones, and lower BMD values than the group taking conventional antipsychotic medication. These findings suggest that the high rates of osteoporosis associated with schizophrenia may result from hypogonadism secondary to antipsychotic-induced hyperprolactinemia, and that the prolactin-raising profile of antipsychotic drugs should be considered when choosing an antipsychotic drug.
Available from: Robert P Mcmahon
- "Hyperprolactinemia is known to increase the risk of bone mineral density (BMD) loss in patients with schizophrenia with long term antipsychotic drug treatment, either through secondary hypogonadism  or hyperprolactinemia itself . Previous studies have demonstrated that between 32-65% of patients treated with antipsychotic drugs suffer from bone mineral loss, leading to osteoporosis [74,76]. Bone fractures occur more frequently in people with schizophrenia taking antipsychotics than in the nonpsychiatric population [77,78]. "
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ABSTRACT: Prolactin elevations occur in people treated with antipsychotic medications and are often much higher in women than in men. Hyperprolactinemia is known to cause amenorrhea, oligomenorrhea, galactorrhea and gynecomastia in females and is also associated with sexual dysfunction and bone loss. These side effects increase risk of antipsychotic nonadherence and suicide and pose significant problems in the long term management of women with schizophrenia. In this manuscript, we review the literature on prolactin; its physiology, plasma levels, side effects and strategies for treatment. We also present the rationale and protocol for an ongoing clinical trial to treat symptomatic hyperprolactinemia in premenopausal women with schizophrenia. More attention and focus are needed to address these significant side effects and help the field better personalize the treatment of women with schizophrenia.
Available from: Jingping Zhao
- "Although the high incidence rate of osteoporosis and osteoporotic fractures in the schizophrenic patients was first reported about 20 years ago   , related reports about the increased risk of osteoporotic fracture and earlier onset of osteoporosis in the schizophrenic patients are seldom published . Recently, many papers have presented convincing evidence that decrease of bone mineral density is related to schizophrenia particularly in patients treated with psychotropic medication    . "
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ABSTRACT: Schizophrenia is one of the most common global mental diseases, with prevalence of 1%. Patients with schizophrenia are predisposed to diabetes, coronary heart disease, hypertension, and osteoporosis, than the normal. In comparison with the metabolic syndrome, for instance, there are little reports about osteoporosis which occurs secondary to antipsychotic-induced hyperprolactinaemia. There are extensive recent works of literature indicating that osteoporosis is associated with schizophrenia particularly in patients under psychotropic medication therapy. As osteoporotic fractures cause significantly increased morbidity and mortality, it is quite necessary to raise the awareness and understanding of the impact of antipsychotic-induced hyperprolactinaemia on physical health in schizophrenia. In this paper, we will review the relationship between schizophrenia, antipsychotic medication, hyperprolactinaemia, and osteoporosis.
Available from: Leah H Rubin
- "In this context, the clinical relationship between prolactin elevation and changes in bone density appears to correlate with menstrual dysregulation in women. In studies of patients with prolactin elevation during chronic antipsychotic treatment, hypogonadism has also been observed [Smith et al. 2002; Kinon et al. 2003; Huber et al. 2005; O'Keane and Meaney, 2005; Kishimoto et al. 2008]. Studies in rodents and nonhuman primates also illustrate that chronic treatment with risperidone lowers BMD by increasing bone resorption [Kunimatsu et al. 2010; Sackett et al. 2010], and that this increase in resorption is related to prolactin elevation and reductions in estrogen. "
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ABSTRACT: Prolactin elevation has been proposed as a risk factor for low bone density and potentially osteoporosis in patients on long-term treatment with prolactin-elevating antipsychotics. Our objective was to study the acute effects of prolactin elevation on serum markers of bone formation and resorption in patients treated with risperidone.
Thirty participants meeting Diagnostic and Statistical Manual of Mental Disorders fourth edition criteria for schizophrenia, major depressive disorder with psychotic features, or bipolar disorder with psychosis were enrolled. At baseline, subjects were antipsychotic free. Subjects were evaluated before and after 4 weeks of risperidone treatment. Assessments included symptom ratings along with testosterone, estradiol, prolactin, osteocalcin (marker of bone formation), and n-telopeptide crosslinks (NTx marker of bone resorption). Primary analysis examined the impact of risperidone treatment on change in the bone markers and hormone levels from pre to post treatment.
Prolactin levels significantly increased from 12.1 ± 1.9 ng/ml to 65.7 ± 12.2 ng/ml after treatment (p < 0.001). NTx markers of bone resorption significantly decreased from 18.31 ± 1.49 nM bone collagen equivalent (BCE) before treatment to 15.50 ± 1.22 nM BCE after treatment in the study sample as a whole (p < 0.05). A trend was observed indicating that NTx may increase in individuals who have the greatest increases in prolactin after treatment r = 0.33, p = 0.07).
These findings suggest that prolactin elevation is associated with changes in bone physiology very early in the course of treatment with risperidone. Bone resorption decreased in many subjects but higher levels of bone resorption occurred in patients with the greatest increases in prolactin. This may have important implications for prolactin monitoring or the periodic assessment of osteoporosis-related outcomes in patients requiring extended treatment.
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