Osteoporosis is characterized by decreased bone mass and disrupted bone architecture, which reduce bone strength and increase the risk of fracture. Bisphosphonates, although poorly absorbed from the gut when given orally, are preferentially localized to the skeleton where they inhibit bone resorption. This provides the rationale for their use in the treatment of diseases of high bone turnover, such as Paget's disease and hypercalcemia of malignancy. The antiresorptive action of bisphosphonates is also useful in the management of osteoporosis, in which the rate of bone resorption exceeds that of bone formation. Cyclical etidronate and alendronate are the most extensively studied bisphosphonates in the management of osteoporosis, but limited data are also available for pamidronate, clodronate, tiludronate, and risedronate. All bisphosphonates have a similar rate of action, and their efficacy in increasing spinal bone mass in women with postmenopausal osteoporosis is broadly comparable over 2 to 3 years. The increase in spinal bone mass achieved with cyclical etidronate is associated with at least a 50% decrease in vertebral fracture rate, which is comparable to that seen with hormone replacement therapy, calcitonin, and, in preliminary data, for alendronate. Both cyclical etidronate and alendronate increase hip bone mass in patients with osteoporosis. The long-term safety data available for cyclical etidronate are generally favorable; clinical osteomalacia has not been experienced with the cyclical regimen during 7 years of treatment. Comparable long-term safety data are not yet available for the other bisphosphonates. The most common adverse events with oral bisphosphonate treatment are mild gastrointestinal disturbances, with an incidence rate generally similar to that with placebo and/or calcium. There have been reports, however, of erosive esophagitis during treatment with oral pamidronate and a higher incidence of abdominal pain during treatment with alendronate than with placebo and/or calcium; both of these compounds are amino bisphosphonates. Extensive experience with cyclical etidronate has established its long-term efficacy and safety. Long-term data are needed for the newer bisphosphonates, in order to position them correctly alongside the various other therapeutic options available for the successful management of osteoporosis.
