Skeletal safety of tiludronate

The medical uses of bisphosphonates derive from their exceptional ability to inhibit bone resorption. However, bone resorption is essential for the healing of fractures, the repair of microscopic fatigue cracks in bone, nad the internal reorientation of trabecular and cortical bone in response to altered mechanical strains. In theory, overdose with bisphosphonates might interfere with the repair of fractures or weaken bone strength (by forcing bones to accumulate and propagate fatigue cracks or by abolishing the skeleton's adaptive powers). Regulatory agencies (particularly in the USA) have, therefore, set comprehensive and stringent safety criteria before the marketing of bisphosphonates can be approved. Some bisphosphonates can also inhibit bone mineralization, alter hepatic function, or cause gastritis/esophagitis. The safety profile of tiludronate will be described from this perspective, emphasizing the results of prolonged treatment in animals, and studies in humans.