Osteoporosis is a systemic skeletal condition characterized by low bone mass and microarchitectural deterioration of bone tissue that increases bone fragility and risk for fractures. Osteoporosis may occur without a known cause, or secondary to another condition. These include corticosteroid therapy, excessive alcohol use, primary or secondary hypogonadism, low calcium intake, vitamin D deficiency, smoking, antiepileptic drug use, thyrotoxicosis, primary hyperparathyroidism, chronic liver or kidney disease, rheumatoid arthritis, diabetes, human immunodeficiency virus, organ transplantation, multiple myeloma, and others. Osteoporosis is diagnosed in individuals on the basis of presence of a fragility fracture or by bone mass measurement criteria. A fragility fracture results from forces that would not normally cause a fracture, such as a hip or wrist fracture from falling from standing height or a vertebral compression fracture. Although specific fracture sites have been considered more characteristic of osteoporosis, fractures occurring at nearly every anatomical site have been associated with osteoporosis. This systematic evidence review is an update for the U.S. Preventive Services Task Force (USPSTF) recommendation on screening for osteoporosis. In 2002, based on results of a previous review, the USPSTF recommended bone density screening for women age greater than or equal to 65 years and women age 60-64 years at increased risk for osteoporotic fractures. They made no recommendations for or against screening postmenopausal women age less than 60 years or women age 60-64 years without increased risk. Men were not considered in the prior recommendation. This update focuses on new studies and evidence gaps that were unresolved at the time of the 2002 recommendation. These include the effectiveness and harms of osteoporosis screening in reducing fractures and fracture-related health outcomes for men as well as postmenopausal women without known previous fractures; the performance of risk-assessment instruments and bone measurement tests in identifying individuals with osteoporosis; optimal screening intervals; and efficacy and harms of medications to reduce primary fractures in a screening-detected population. Based on evidence gaps identified from the previous review and using the methods of the USPSTF, the USPSTF and Agency for Healthcare Research and Quality (AHRQ) developed Key Questions for this review. Investigators created an analytic framework incorporating the Key Questions and outlining the patient populations, interventions, outcomes, and harms of the screening process. The target populations include postmenopausal women and men age greater than 50 years without known previous osteoporosis-related fragility fractures or secondary causes of osteoporosis. Key Questions include: 1. Does screening for osteoporosis and low bone density reduce osteoporosis-related fractures and/or fracture-related morbidity and mortality in the target populations? These include postmenopausal women (age less than 60 years, 60-64 years at increased risk for osteoporotic fractures, 60-64 years not at increased risk for osteoporotic fractures, and greater than or equal to65 years) and men less than 50 years. 2. What valid and reliable risk-assessment instruments stratify women and men into risk categories for osteoporosis or fractures? 3. A. How well does DXA predict fractures in men? B. How well do peripheral bone measurement tests predict fractures? C. What is the evidence to determine screening intervals for osteoporosis and low bone density? 4. What are the harms associated with osteoporosis screening? 5. Do medications for osteoporosis and low bone density reduce osteoporosis-related fracture rates and/or fracture-related morbidity and mortality in the target populations? 6. What are the harms associated with medications for osteoporosis and low bone density?