Abstract Introduction Severe Mental Illness (SMI), particularly schizophrenia, has been associated with reduced bone mineral density and increased risk of fractures, although some studies have shown inconsistent results. We aimed to examine the effect of SMI on recorded diagnosis of osteoporosis and fragility fracture in older people in the UK, accounting for age, sex, social deprivation and lifestyle factors (smoking, alcohol and Body Mass Index (BMI)). Methods We used de-identified data provided as part of routine primary care (IQVIA Medical Research Database). Patients with a diagnosis of SMI (schizophrenia, bipolar disorder, other psychosis) aged 50-99y between 1/1/2000-31/12/2018 were matched 1:8 to age- and sex-adjusted controls without SMI, using Exposure Density Sampling (EDS). We estimated Hazard Ratios (HR) and 95% Confidence Intervals (95%CI) based on Cox Proportional Hazards model. We stratified the analysis by sex, accounting for age, social deprivation, year (model 1), and the above plus smoking, alcohol, and BMI (model 2). We imputed missing lifestyle data using Multiple Imputation. Results In total 444,480 people aged ≥50 years were included in the analysis (SMI N=50,006; controls N=394,474). In men, prior diagnosis of SMI increased the risk of osteoporosis diagnosis by 64% (HR 1.64; 95%CI 1.44-1.88) and the risk of fragility fractures by 87% (HR 1.87; 95%CI 1.70-2.06) in model 1. SMI also increased osteoporosis risk by 49% (HR=1.49; 95%CI 1.30-1.71) and fragility fracture risk by 82% (HR=1.82; 95%CI 1.65-2.00) in model 2 in men. In contrast, prior diagnosis of SMI had no significant effect on recorded osteoporosis risk in women. Prior SMI in women increased fragility fracture risk by 53% (HR 1.53; 95%CI 1.45-1.61) in model 1 and by 51% (HR=1.51; 95%CI 1.43-1.58) in model 2. Conclusions SMI is associated with increased risk of osteoporosis in men, and fragility fractures in both men and women, with a greater effect in men.
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