Effects of minodronate on cortical bone response to mechanical loading in rats

Abstract

The effects of BPs on bone formation during mechanical loading are still unknown. In this study, we evaluated the effect of minodronate on the cortical bone response to mechanical loading applied using a 4-point bending device. We used six-month old female Wistar rats and randomized into five groups (N=10/group): Vehicle administration (VEH), low dose minodronate administration (MIN-L, 0.01 mg/kg BW), middle dose minodronate administration (MIN-M, 0.1mg/kg BW), high-dose minodronate administration (MIN-H 1mg/kg BW), and very high-dose minodronate administration (MIN-VH, 10mg/kg BW). Minodronate or vehicle was administered orally using the feeding needle at a dosage 3 times/week for 3 weeks. Loads on the right tibia at 38 N for 36 cycles at 2 Hz were applied in vivo by 4-point bending on the same day for 3 weeks. After calcein double labeling the rats were sacrificed and tibial cross sections were prepared from the region with maximal bending at the central diaphysis. Histomorphometry was performed at the entire periosteal and endocortical surface of the tibiae, dividing the periosteum into lateral and medial surfaces. The formation surface was reduced significantly in MIN-H and MIN-VH groups at the medial surface, and in MIN-VH group at the endocortical surface of the loaded tibia (p<0.01 vs. VEH). The mineral appositional rate was reduced significantly in MIN-H and MIN-VH groups at the endocortical surface of the loaded tibia (p<0.01 vs. VEH). The bone formation rate was significantly reduced in MIN-H group at the medial surface, and in MIN-H and MIN-VH groups at the endocortical surface of the loaded tibia (p<0.01 vs. VEH). However, no significant differences were observed in any parameters between the VEH group and either the MIN-L or MIN-M groups for both the loaded and non-loaded tibiae. Based on previous preventive studies in OVX rats, the optimal dose of minodronate for the treatment of osteoporosis would be 0.03 mg/kg (0.21 mg/kg/week). Therefore, we used 0.1mg/kg of minodronate 3 times/week (0.30 mg/kg/week) that was close to 0.21 mg/kg/week. In conclusion, minodronate does not reduce the cortical bone response to mechanical loading at the optimal dose for the treatment of osteoporosis in rat model.

Localization of Minodronate in Mouse Femora Through Isotope Microscopy

“…[16][17][18] Studies showed that minodronate suppressed bone resorption in ovariectomized rats and cynomolgus monkeys [19][20][21] and affected cortical bone response to mechanical loading in rats. 22 In addition, other in vivo and in vitro studies reported on the high potency of minodronate compared with alendronate regarding the inhibition of bone resorption, 23 with an intermediate mineral-binding affinity. 24 As patients seem to prefer weekly and monthly dosing regimens, 25 long-acting bisphosphonates such as minodronate are gradually becoming the first line of treatment for many prescribing physicians.…”