Tiludronate, a potent
bisphosphonate, has been extensively evaluated in the treatment of
Paget's disease of bone. Its ability to normalize bone turnover without impairing mineralization suggests that
tiludronate represents an important therapeutic advance in the treatment of this progressive and disabling disease. Recent attention has focused on the development of appropriate short- and long-term treatment goals: namely the control of clinical symptoms, such as bone
pain, and the reduction of bone turnover to within normal range, to lessen the risk of developing later complications, such as
deafness,
deformity and walking difficulties. This reduction of bone turnover is the primary aim of treatment. The clinical development of
tiludronate has involved large-scale international multicenter trials. To allow the comparison of results obtained in a variety of clinical settings, great emphasis was placed on the use of consistent methodology across the program. This applied to patient selection, trial design, the evaluation of clinically meaningful effects of treatment and statistical analysis of results. Strict adherence to these principles has allowed us to compare the results of treatment with
tiludronate in 85 centers in six countries across Europe. This paper illustrates the importance of clinical trial design in the evaluation of
tiludronate and
etidronate in the treatment of
Paget's disease of bone, with a brief summary of results obtained from a recent comparative, prospective, double-blind, multicenter clinical trial. Effective suppression of bone turnover was assessed by monitoring the reduction in serum
alkaline phosphatase and the ratio of urinary
hydroxyproline/
creatinine. Reduction in bone
pain was assessed using Huskisson's visual analog scale. The results clearly show that
tiludronate 400 mg/day for 3 months is more effective and as equally well tolerated as
etidronate 400 mg/day.