Mapping the prescriptiome to fractures in men-a national analysis of prescription history and fracture risk

Summary: A nationwide case-control study was performed in 62,865 men aged 50+ using fracture data from the national hospital discharge register to screen all redeemed prescriptions in the past 5 years for significant mapping to fracture risk, employing measures to control for false discovery rate. Introduction: Osteoporosis in men is frequently related to alcohol abuse, hypogonadism, hypercalciuria, or the use of glucocorticoids. Very limited information is available on the impact of other medications on fracture risk in men. Methods: We conducted a nationwide population-based case-control study collecting fracture data from the Danish National Hospital Discharge Register and prescriptions from the National Prescriptions Database (1995-2000). We included men aged 50+ years, with hospital-treated fractures in the year 2000 (n∈=∈15,716), and age- and sex-matched controls (n∈=∈47,149) . Results: We identified 3.2 million redemptions of prescriptions for 1,073 different drugs. The analysis confirmed associations between fracture risk and use of sedatives, anti-epileptics, anti-psychotics, anxiolytics, SSRI, opioids and other analgesics, loop diuretics, and glucorticoids. New associations were also found. We observed an odds ratio (OR [95% CI] for any fracture) for fracture in users of dopaminergic agents (1.6 [1.3-1.9]) and iron compounds (1.2 [1.1-1.5]). The largest impact on fracture risk at population level was exerted by loop diuretics and analgesics. Conclusions: An array of drugs is associated with fracture risk in men. The "prescriptiome" analysis can be used as a surveillance tool for drug-induced osteoporosis and in the planning of preventive measures.