GLOW is an observational, longitudinal, practice-based cohort study of osteoporosis in 60,393 women aged ≥55 years in 10 countries on three continents. In this Review, we present insights from the first 3 years of the study. Despite cost analyses being frequently based on spine and hip fractures, we found that nonvertebral, nonhip fractures were around five times more common and doubled the use of health-care resources compared with hip and spine fractures combined. Fractures not at the four so-called major sites in FRAX® (upper arm, forearm, hip and clinical vertebral fractures) account for >40% of all fractures. The risk of fracture is increased by various comorbidities, such as Parkinson disease, multiple sclerosis and lung and heart disease. Obesity, although thought to be protective against all fractures, substantially increased the risk of fractures in the ankle or lower leg. Simple assessment by age plus fracture history has good predictive value for all fractures, but risk profiles differ for first and subsequent fractures. Fractures diminish quality of life as much or more than diabetes mellitus, arthritis and lung disease, yet women substantially underestimate their own fracture risk. Treatment rates in patients at high risk of fracture are below those recommended but might be too frequent in women at low risk. Comorbidities and the limits of current therapeutic regimens jeopardize the efficacy of drugs; new regimens should be explored for severe cases.