Bone Health in Psychotic Disorders, and Risk Factors for Decreased Bone Health in Established and Early Psychosis

Both schizophrenia and osteoporosis are prevalent and disabling disorders. Risk factors for osteoporosis are highly prevalent in people with psychotic disorders. It remains unclear to date as to what are the main drivers of reduced bone mineral density (BMD) in schizophrenia. In this PhD I reviewed risk factors associated with reduced bone mineral density and osteoporosis in schizophrenia. In cross sectional and longitudinal studies in first episode psychosis (FEP) and established psychosis cohorts, I investigated recognised risk factors (serum prolactin, vitamin D deficiency and smoking) for reduced BMD to establish: a) their prevalence; and b) their relationship with mental and physical clinical state measures.

We conducted a systematic review and meta-analysis to identify the skeletal sites at which reduced bone mineral density most commonly occurs in schizophrenia compared with healthy control subjects. We found that those with schizophrenia have a significantly reduced BMD (osteopenia and osteoporosis) at both the lumbar spine and the hip- and this is associated with hyperprolactinaemia (HPL) and smoking.

From 174 people with FEP, 43% (n=74) had hyperprolactinaemia (HPL), whilst 27% (n=21/78) and 27% (n=26/95) had HPL at 3 and 12 months respectively. Prolactin levels were consistently higher in patients taking risperidone, amisulpride and first generation antipsychotics (FGAs) compared to other antipsychotics.

The prevalence of cigarette smoking was 78% in FEP and 62% in established psychosis. As well as smoking being a recognised risk factor for poor bone health, being a highly nicotine dependent smoker was significantly associated with PANSS positive symptom scores (F= 5.480 p= 0.004), and decreased scores on the Rosenberg self-esteem scale (F=3.261, p=0.039) in established psychosis.

In FEP, 80% had suboptimal vitamin D levels (n=124) at first contact, and 76=% at 12 months follow up. Higher baseline vitamin D levels were prospectively associated with lower total PANSS (β=-0.24,95%CI=-0.47— 0.01, p=0.04) and PANSS negative symptom scores ((β=-0.12,95%CI=- 0.23—0.01, p=0.04) at 12 months. In established psychosis, 86% (n=279) had suboptimal vitamin D levels, with lower vitamin D associated with increased cardiovascular disease risk factors and in particular metabolic syndrome, although not with clinical state measures in established psychosis.

This PhD identified high prevalence rates of vitamin D deficiency and smoking in early and established psychosis, and HPL in early psychosis, all known risk factors for osteoporosis in schizophrenia. Evidence indicates a role for vitamin D, prolactin and smoking in the pathogenesis of osteoporosis in schizophrenia, and novel links were identified between vitamin D and increased psychotic symptoms and cardiometabolic risk factors. However the protective effect of vitamin D supplementation is not yet known.

Further research is required to ascertain the aetiology of reduced BMD in schizophrenia, and to investigate if amelioration of risk factors such as HPL, smoking and vitamin D deficiency, can impact on low bone mass and clinical symptoms in early psychosis and schizophrenia.