Epidemiological aspects of drug-related vitamin D deficiency and osteoporotic fractures

Sammanfattning: Background: Vitamin D deficiency, secondary osteoporosis and low-energy fractures (LEF) as side effects of specific drugs were first described more than half a century ago. These effects are recognized in guidelines where patients prescribed risk drugs are recommended follow-up with testing and supplementation. How these drugs are managed within Swedish healthcare has not been previously investigated. Aim: To study epidemiological aspects of drug-related vitamin D deficiency and osteoporotic fractures.Methods: The association between drugs for continual use and vitamin D levels in the elderly was investigated in a clinical study including more than 550 patients (paper I). Real-world data on drug prescriptions, laboratory testing and demographic variables from electronic health records were thereafter used to assess the clinical management and vitamin D levels. More than 12 000 patients prescribed risk drugs were included in this cross-sectional study (paper II). Focus group interviews were then undertaken to explore determinants of risk drug management among physicians from seven primary care centers. Thematic analysis with an inductive approach was used to create a framework addressing adherence to medical guidelines (paper III). Finally, a multifactorial risk assessment tool was developed from LEF risk factors in more than    15 000 patients prescribed antiepileptic risk drugs in a retrospective open cohort study (paper IV).Results: A weak inverse association between the number of prescribed drugs and levels of vitamin D was found (paper I). Fewer than one in fifteen patients prescribed risk drugs were tested for vitamin D while close to a third were supplemented. Differences in management and vitamin D levels with regard to type of risk drug were found (paper II). Awareness levels, expressed beliefs and perceived responsibility were reasons behind these differences (paper III). The Kalmar Epilepsy Fracture Risk Index (KEFRI) confirmed previously suggested risk factors (paper IV). Conclusions: Drugs generating vitamin D deficiency, secondary osteoporosis and LEF are often overlooked in healthcare. Awareness and attitudes need to be improved and strategies to better manage patients prescribed these drugs are required in order to avoid unnecessary side effects. The KEFRI could aid clinicians in treatment decisions, potentially reducing fracture risks in specific patient groups.