Tiludronate: development as an osteoporosis therapy

The clinical development of tiludronate (tiludronic acid, disodium salt) for the treatment of Paget's disease of bone is now being complemented by another clinical trials program to investigate its use in osteoporosis. It is expected that osteoporosis will become a major indication for tiludronate, and this paper describes the trial design and treatment goals that will be employed in these new studies. In studies to assess the incidence of fracture, the primary efficacy end point is the occurrence of vertebral fractures after 3 years of therapy. Secondary end-points include changes in lumbar bone mineral density, spinal deformity index, and height. Changes in biochemical markers and quality of life will also be assessed. Safety evaluations include clinical laboratory parameters, adverse events and, in selected patients, histomorphometry of the iliac crest bone. For the nonfracture studies, the primary efficacy end-point is the effect on bone mineral density after 2 years of therapy. Secondary end-points include vertebral fracture rate, spinal deformity index, and height. Biochemical markers, quality of life, and safety (including bone biopsies in selected patients) will be evaluated as in the fracture studies. The studies are expected to be completed in early 1997, followed by worldwide regulatory applications in late 1997.