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Bisphosphonates for the prevention and treatment of osteoporosis. Osteoporosis is a systemic skeletal disorder characterized by bone loss, which leads to impaired bone strength and an increased risk of fractures. Two million fractures are attributed to osteoporosis annually in the United States and they are associated with serious morbidity and mortality. Bisphosphonates reduce the risk of fracture by suppressing bone resorption and increasing bone strength, and they have been widely used for the prevention and treatment of osteoporosis. However, the use of these drugs for the management of osteoporosis remains a clinical challenge. There are several important considerations including appropriate patient selection, pretreatment evaluation, potential adverse effects, patient preferences, and adherence. This review will discuss the evidence informing the clinical strategy for using bisphosphonates in patients with osteoporosis and those at high risk of fracture, focusing on the benefits and risks of treatment. We will also consider issues related to the monitoring and duration of treatment.