Longitudinal effect of tiludronate on bone mineral density, resonant frequency, and strength in monkeys

The effect of Tiludronate on bone was studied in 72 growing monkeys (Papio papio), 36 males and 36 females, aged 4-7 years. They were randomly allocated into four groups (18 animals per group, 9 males and 9 females): group I, controls; group II, 10 mg/kg/day; group III, 20 mg/kg/day; and group IV, 40 mg/kg/day of Tiludronate. A total of 12 animals (6 males and 6 females) in each group were sacrificed at the end of treatment (1 year) and 6 animals (3 males and 3 females) per group 1 year later. Bone mineral density (BMD) was measured by dual-photon absorptiometry. Biomechanical properties were evaluated by an impact torsion test and by resonant frequency analysis. Bone mineral measurements indicated that at the end of 1 year of treatment BMD was significantly higher, especially at the distal epiphysis of the radius, than in controls. No significant differences between groups were found in BMD 1 year after stopping treatment. Biomechanical analyses indicated that torsional stiffness increased after treatment. No differences between groups were found 1 year after stopping treatment. Results of resonant frequencies indicated an increased calculated transversal stiffness after treatment and 1 year later and an increased buckling strength 1 year after stopping treatment. In conclusion, the results on the effect of Tiludronate in growing monkeys indicate a profound effect of this drug on bone density and biomechanical properties. The biomechanical results indicate that this drug is safe, with conservation of bone strength despite a change in intrinsic mechanical properties of the bone.