Treatment of bone diseases with bisphosphonates, excluding osteoporosis

The main biologic action of bisphosphonates consists of the inhibition of o steoclastic bone resorption, and, at least, for the drugs introduced after etidronate, without any significant inhibition of bone mineralization. Bisp hosphonates therefore play a major role in conditions that are characterize d, at least partly, by an increased bone resorption. Primary and secondary osteoporosis by far constitute the most widespread indications for bisphosp honates, mostly because recent published trials have demonstrated their abi lity to prevent fractures. Potentially crippling conditions such as symptom atic Paget disease of bone remain a major therapeutic challenge for bisphos phonates, but the prevention of the major complications such as sarcoma has still to be proven. The availability of more potent bisphosphonates, less toxic for bones, has certainty widened the therapeutic interventions to asy mptomatic patients, bearing in mind the various potential troublesome compl ications. Fibrous dysplasia resembles, in certain aspects, Paget disease; i t is therefore not surprising that bisphosphonate therapy has been proposed in this indication. With the aging of world populations, more and more can cers will be diagnosed. For those with a bone metastatic propensity or mali gnant hematologic condition, such as multiple myeloma, the most recent gene ration of more potent bisphosphonates may bring more comfort to crippled pa tients and even, hopefully, have a direct antitumoral activity, if used syn ergistically with the armamentarium already available to the clinician. New indications for bisphosphonates include osteogenesis imperfecta both in ch ildren and adults. In the future, they might be used in the prevention of e rosions in rheumatoid arthritis and of loosening of joint prostheses, as we ll as possibly in osteoarthritis. Now that the fear of theoretically freezi ng bone remodeling has been reasonably dismissed, potential uses for bispho sphonates might be considered nearly infinite. (C) 2000 Lippincott Williams & Wilkins, Inc.