Bisphosphonates in the treatment of osteoporosis in 1997: A review

Osteoporosis is characterized by a reduction of bone in the skeleton, associated with skeletal fragility and an increased risk of fracture after minimal trauma. The three major osteoporotic fractures are those of the forearm, vertebral body, and hip, although fractures of the humerus, tibia, pelvis, and ribs are also common: Osteoporotic fractures are a major cause of morbidity and mortality, and lead to increased health and social service expenditures in both sexes. The main objective in treating patients with osteoporosis is to reduce the risk of fractures. Bisphosphonates are an important group of therapeutic agents for the management of osteoporosis, as they inhibit bone resorption and increase bone density, thereby potentially decreasing fracture risk. The demonstration of a reduction in fracture incidence requires large randomized, double-masked, placebo-controlled trials with the statistical power to detect increases in bone density and a significant reduction in fracture incidence. Although cyclical etidronate apparently decreases the risk of vertebral fractures in a manner comparable with hormone replacement therapy and calcitonin, there are no randomized controlled trials that show a reduction in forearm or hip fractures. Alendronate is the only agent that has been shown in large randomized controlled trials to statistically significantly decrease the risk of symptomatic fractures of the forearm, spine, and hip by 48%, 55%, and 51%, respectively. In addition to the efficacy of any treatment for osteoporosis, compliance and tolerability must also be satisfactory. The most common adverse events with cyclical etidronate and alendronate are mild gastrointestinal disturbances, but the incidence is similar to that seen with placebo or calcium. In clinical practice, esophagitis has been rarely reported with alendronate, and in the majority of cases, this effect is related to a failure to follow the recommendations for administration. Although cyclical etidronate therapy may lead to histologic evidence of focal osteomalacia, clinical osteomalacia has not been observed when the recommended cyclical regimen has been used. Iliac crest bone biopsies show no evidence of a mineralization defect with alendronate. Long-term data on bone density and fracture incidence are needed from large-scale controlled studies with other bisphosphonates, such as clodronate, tiludronate, risedronate, and ibandronate, to position them correctly alongside other therapeutic alternatives for the treatment of osteoporosis.