The bisphosphonates are long-lived synthetic analogs of pyrophosphate, a natural, short-lived inhibitor of bone. Oral doses share similar qualities (ie, they inhibit bone resorption, poor absorption, and potential gastrointestinal irritants), but each one has a unique spectrum of potency and a probable mechanism of action. The parent compound, etidronate, was first used in multicentered trials for the treatment of primary osteoporosis and showed some success in increasing bone density and perhaps controlling fracture rates. The recently approved drug alendronate is a more potent agent than etidronate, produces a greater increase in bone density, and decreases fractures. Oral and intravenous pamidronate have similar positive effects on bone density. Studies with tiludronate, risedronate, and clodronate show similar promise as therapeutic agents.