SCHIZOPHRENIA AND OSTEOPOROSIS - Nikolić, Tatjana P; Petronijević, Nataša D (Medicinski podmladak, 2018)
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, metabolic side effects, decrease of bone mineral density (BMD) and osteoporotic fractures often follow treatment with antipsychotics. 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 are the observed changes of bones consequence of disease process itself or antipsychotics together with characteristic life style of patients that usually include smoking, poor nutrition, sedentary and   low vitamin D, are responsible.  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 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. Key words: schizophrenia, antipsychotics, bone mineral density, osteoporosis, hyperprolactinemia SAŽETAK Shizofrenija (schizophrenia, SCH) je kompleksno mentalno oboljenje koji pogađa oko 1% populacije. SCH se karakteriše pozitivnim simptomima, negativnim simptomima i kognitivnom disfunkcijom. SCH pacijenti često zahtevaju dugotrajno lečenje antipsihoticima. Nažalost, tretman antipsihoticima često je povezan sa neželjenim metaboličkim efektima, smanjenom koštanom mineralnom gustinom (bone mineral density, BMD) i osteoporotičnim prelomima. Osteoporoza je degenerativna bolest koju karakteriše smanjena čvrstina kostiju, značajno smanjena koštana mineralna gustina, fragilnost pršljenova i ostalih kostiju, prelomi i narušena koštana mikroarhitektura. Smanjenje BMD i povećani rizik od preloma su uočeni kod SCH pacijenata koji su na dugoročnoj terapiji antipsihoticima. Međutim, promene koštane mase i metaboličkih parametara su takođe uočene kod pacijenata koji nisu primali terapiju. Još uvek nije razjašnjeno da li su uočene promene karakteristika same bolesti ili način života obolelih (pušenje, sedentarni način života, ishrana, nedostatak vitamina D) zajedno sa tretmanom antipsihoticima dovode do smanjenja koštane mase. Mehanizmi kojima antipsihotici uzrokuju osteoporozu su izuzetno kompleksni. Pretpostavlja se da je nastanak hiperprolaktinemije najverovatniji. Hiperprolaktinemija može direktno uticati na metabolizam kostiju stimulisanjem resorpcije koštanog tkiva i remećenjem formiranja kostiju. Takođe, dugotrajna hiperprolaktinemija može uzrokovati hipogonadotropni hipogonadizam, sa posledičnim smanjenjem sekrecije polnih hormona koji značajno utiču na metabolizam kostiju. Homeostaza kostiju je takođe regulisana preko hipotalamo-hipofizno-adrenalne (HPA) osovine. Disregulacija HPA osovine se često opisuje kod obolelih od shizofrenije. Perinatalna primena fenciklidina (phencyclidine, PCP) pacovima predstavlja animalni model SCH. Ovaj model je pogodan za ispitivanje da li su promene na kostima posledica same bolesti ili primenjenih antipsihotika. Štaviše, može se koristiti za rasvetljavanje mehanizma delovanja fenciklidina i hroničnog tretmana antipsihoticima na koštanu strukturu i telesni sastav, a u cilju prevencije nastanka osteoporoze. Ključne reči: shizofrenija, antipsihotici, koštana mineralna gustina, osteoporoza, hiperprolaktinemija