The incidence of fragility fractures begins to increase in middle age. We investigated prospectively risk factors for low-energy fractures in men and women, and specifically for forearm, proximal humerus, vertebral, and ankle fractures. The population-based Malmö Preventive Project consists of 22,444 men and 10,902 women, mean age 44 and 50 years, respectively, at inclusion. Baseline assessment included multiple examinations and lifestyle information. Mean follow-up was 19 and 15 years for men and women, respectively, regarding incident fractures. Fractures were ascertained from radiographic files. At least one low-energy fracture occurred in 1,262 men and 1,257 women. In men, the risk factors most strongly associated with low-energy fractures were diabetes [relative risk (RR) 2.38, confidence interval (CI) 95% 1.65-3.42] and hospitalization for mental health problems (RR 1.92, CI 95% 1.47-2.51). Factors associated with mental health and lifestyle significantly increased the fracture risk in most of the specific fracture groups: hospitalizations for mental health problems (RR 2.28-3.38), poor appetite (RR 3.05-3.43), sleep disturbances (RR 1.72-2.95), poor self-rated health (RR 1.80-1.83), and smoking (RR 1.70-2.72). In women, the risk factors most strongly associated with low-energy fractures were diabetes (RR 1.87, CI 95% 1.26-2.79) and previous fracture (RR 2.00, CI 95% 1.56-2.58). High body mass index (BMI) significantly increased the risk of proximal humerus and ankle fractures (RR 1.21-1.33) while, by contrast, lowering the risk of forearm fractures (RR 0.88, CI 95% 0.81-0.96). Risk factors for fracture in middle-aged men and women are similar but with gender differences for forearm, vertebral, proximal humerus, and hip fracture whereas risk factors for ankle fractures differ to a certain extent. The risk-factor pattern indicates a generally impaired health status, with mental health problems as a major contributor to fracture risk, particularly in men.