THE ROLE OF BISPHOSPHONATES IN THE TREATMENT OF OSTEOPOROSIS

Bisphosphonates, previously called diphosphonates, are potent inhibito rs of bone resorption and interfere with several stages of the osteore sorption process. Different mechanisms of action, acting simultaneousl y and synergistically, are likely to be involved. Several bisphosphona tes were tested in various clinical situations related to an increase in osteoclastic resorption. Studies evaluating the effects of clodrona te in osteoporosis have been conducted either with too few patients or with inadequate methodology. The observation of a significant decreas e in the rate of vertebral fractures in patients whose bone mineral de nsity oi the spine was below 50th percentile of distribution of bone m ineral density in osteoporotic patients and concurrently had more than two prevalent fractures, with etidronate given for 3 years suggest a possible role of this bisphosphonate in the treatment of severe osteop orosis. Alendronate was recently shown to reduce vertebral and nonvert ebral fractures in women with osteoporosis. However, particular recomm endations for alendronate intake are required to reduce the risk of ga strointestinal side effects. The development of the oral form of pamid ronate was jeopardized by reports of erosive esophagitis which appears to be a common feature of all aminobisphosphonates. The preliminary r esults shown with the continuous daily oral intake of ibandronate do n ot compare favorably with other bisphosphonates on the market or being developed for osteoporosis. Preliminary results with 5 mg risendronat e, given either continuously or intermittently, are promising. Demonst ration of the minimal effective dose of this compound for treatment of postmenopausal osteoporosis will be obtained from long-term clinical trials. Tiludronste was previously shown to prevent early postmenopaus al bone loss. A large currently ongoing clinical program will evaluate the effects of this compound in reduction of fracture.