This study predicts the incidence and economic burden of osteoporosis-related fractures in the United States from 2005 to 2025, by sex, age group, race/ethnicity, and fracture type. In 2005, over 2 million fractures were predicted, costing nearly $17 billion. Men accounted for 29% of fractures and 25% of costs. The most rapid growth in disease burden is projected among nonwhite populations. By 2025, annual fractures and costs are expected to rise by almost 50%, with a 87% increase for those aged 65–74 and a 175% increase for Hispanic and other subpopulations. Total costs including prevalent fractures are projected to exceed $19 billion in 2005. The study highlights the need for targeted interventions across all skeletal sites, not just hip and vertebral, and emphasizes the importance of addressing men and diverse race/ethnicity subgroups. The model used a Markov state-transition approach to estimate fractures and costs, incorporating data on fracture incidence, mortality, and unit costs. Sensitivity analyses showed that changes in unit costs and incidence rates significantly impacted the results. The study underscores the growing burden of osteoporosis-related fractures and the need for effective prevention, treatment, and education efforts. The findings emphasize the importance of addressing the increasing burden in nonwhite populations and the need for targeted interventions to reduce the economic and health impacts of osteoporosis.This study predicts the incidence and economic burden of osteoporosis-related fractures in the United States from 2005 to 2025, by sex, age group, race/ethnicity, and fracture type. In 2005, over 2 million fractures were predicted, costing nearly $17 billion. Men accounted for 29% of fractures and 25% of costs. The most rapid growth in disease burden is projected among nonwhite populations. By 2025, annual fractures and costs are expected to rise by almost 50%, with a 87% increase for those aged 65–74 and a 175% increase for Hispanic and other subpopulations. Total costs including prevalent fractures are projected to exceed $19 billion in 2005. The study highlights the need for targeted interventions across all skeletal sites, not just hip and vertebral, and emphasizes the importance of addressing men and diverse race/ethnicity subgroups. The model used a Markov state-transition approach to estimate fractures and costs, incorporating data on fracture incidence, mortality, and unit costs. Sensitivity analyses showed that changes in unit costs and incidence rates significantly impacted the results. The study underscores the growing burden of osteoporosis-related fractures and the need for effective prevention, treatment, and education efforts. The findings emphasize the importance of addressing the increasing burden in nonwhite populations and the need for targeted interventions to reduce the economic and health impacts of osteoporosis.