Risedronate improves bone architecture and strength faster than alendronate in ovariectomized rats on a low-calcium diet

Clinical evidence suggests that, compared with alendronate, risedronate reduces fracture risk faster and more potently, with less bone mass gain. We tested the hypothesis that risedronate improves bone quality faster than alendronate using calcium-deficient, ovariectomized (OVX) rats. Female Sprague–Dawley rats at 24 weeks of age were divided into sham-operated and OVX groups and fed a low-calcium (0.05 %) diet under paired feeding. After 12 weeks, OVX rats were divided into five groups and treated with vehicle, risedronate (3.5 and 17.5 μg/kg/week, s.c.) or alendronate (7 and 35 μg/kg/week, s.c.). Rats were killed 6–8 weeks later and the bone architecture and strength of the left femur were evaluated by micro-computed tomography and a three-point bending test. Trabecular bone mineral density (BMD), number and thickness were significantly lower in OVX rats than in the sham-operated group. Cortical BMD, bone area (Ct.Ar), and thickness (Ct.Th) were similarly decreased. Risedronate significantly improved Ct.Ar (+8 %) and Ct.Th (+9 %) at 6 weeks, while alendronate only caused a significant improvement in Ct.Ar (+8 % at 6 weeks) and only at the higher dose. At 8 weeks, both risedronate and alendronate significantly increased trabecular BMD compared with the vehicle. Bone strength parameters showed a significant correlation between Ct.Ar and Ct.Th. Risedronate significantly improved maximum load at 6 weeks, while alendronate failed to produce any significant changes. Our results suggest that risedronate is superior to alendronate at improving cortical bone architecture and strength, and that enhanced bone quality partly accounts for risedronate’s efficacy.