Schizophrenia and osteoporosis

Schizophrenia (SCH) is a complex mental disorder that affects about 1% of the population. SCH is characterized by positive symptoms, negative symptoms and cognitive impairment. SCH patients often require a long-term treatment with antipsychotics. Unfortunately, treatment with antipsychotics can often be followed with metabolic side effects, decrease of bone mineral density (BMD) and osteoporotic fractures. Osteoporosis is a degenerative disease characterized by decreased bone stiffness, as signified by low bone mineral density, vertebral or nonvertebral fragility fractures and disruption of bone microarchitecture. Decreased BMD and increased incidence of fractures are described in SCH patients treated for a long time with antipsychotics . On the other hand, deterioration of bones and metabolic disturbances are seen in SCH patients who have never received antipsychotics. It remains unclear if the observed changes of bones consequence of disease process itself or antipsychotics are responsible, together with characteristic life style of patients that usually include smoking, poor nutrition, sedentary and low vitamin D. The mechanisms of antipsychotic-induced osteoporosis are complex. The most possible one is hyperprolactinemia. Hyperprolactinemia might directly affect bone turnover by stimulating bone resorption relative to bone formation. Also, prolonged hyperprolactinemia may cause hypogonadotropic hypogonadism, resulting at the end in impaired suppression of sex hormones and ultimately in changes in bone metabolism. On the other hand, bone remodeling is also controlled by the hypothalamic-pituitary-adrenal (HPA) axis. Dysregulation of HPA axis activity is consistently described in SCH patients. Perinatal phencyclidine (PCP) administration to rodents represents an animal model of SCH. This model is suitable for the investigations if the changes of bones are a consequence of disease itself or applied antipsychotics. Furthermore, it can be used to clarify the mechanism of action of PCP and chronic treatment with antipsychotics on bone structure and body composition, in order to prevent the occurrence of osteoporosis.