Osteoporosis-related nonvertebral fractures increase the risks for morbidity and mortality and add substantially to treatment costs. As an adjunct to controlled, clinical trials, observational studies based on information from large, integrated medical and pharmaceutical claims databases provide an opportunity to assess the "real-world" cost effectiveness of treatment options aimed at reducing osteoporotic fracture risk. Although they lack the stringent controls required to establish causation, these studies include a large treatment population that reflects current disease prevalence, prescribing practices, and treatment-cost patterns in the managed care setting. This article reviews data from key observational studies that used analyses of the large Protocare Sciences Integrated Medical and Pharmaceutical Claims Database, which includes claims and eligibility records for >3 million individuals covered annually under various public and private benefit plans, to explore the cost effectiveness of oral bisphosphonates--risedronate and alendronate--in reducing the risk for nonvertebral fracture. In addition, the data from the Protocare database were used to examine the cost implications of differences in gastrointestinal tolerability in these agents.