IADR Abstract Archives
A novel non-nitrogen-containing bisphosphonate, MPMBP, increases bone mass without adverse effects in neonatal and growing rats
Objectives: Nitrogen-containing bisphosphonates including pamidronate and zoledronate are successfully used to treat conditions such as osteogenesis imperfecta and leukemia, and to reduce the risk of fractures in children. However, concerns regarding their adverse effects persist, since these drugs are known to cause osteonecrosis of the jaw.
In the present study, we examined the efficacy and safety of newly developed non-nitrogen-containing bisphosphonate, [4-(methylthio)phenylthio] methanebisphosphonate (MPMBP), in increasing bone mineral density, in neonatal and growing rats.
Methods: Zoledronate (0.1 mg/kg) or MPMBP (1.2 or 6.0 mg/kg) was injected subcutaneously every three days either from the age of 3 to 18 days or from the age of 3 to 6 weeks. At the end of the experiments, bone and plasma samples were harvested and examined.
Results: The body weight of all rats increased normally in both the zoledronate- and MPMBP-treated groups compared to that in the saline-injected control rats. Bone morphometry analyses using X-ray micro-computed tomography showed that both bisphosphonates increased bone mass and density of the distal femur and proximal tibia; these findings were consistent with our previous findings. Plasma tartrate-resistant acid phosphatase levels decreased in both the zoledronate- and MPMBP-treated groups, whereas plasma bone alkaline phosphatase levels deceased in the zoledronate-treated group but did not change in the MPMBP-treated group compared to those in the controls. Moreover, the zoledronate-treated group showed a marked delay in tooth eruption, whereas the MPMBP-treated group showed eruption of all teeth at the appropriate developmental stage.
Conclusions: In conclusion, these results show that MPMBP has potent anabolic action on bones without adverse effects due to excessive inhibition of bone resorption and/or bone turnover, which limit the clinical use of bisphosphonates in children.
In the present study, we examined the efficacy and safety of newly developed non-nitrogen-containing bisphosphonate, [4-(methylthio)phenylthio] methanebisphosphonate (MPMBP), in increasing bone mineral density, in neonatal and growing rats.
Methods: Zoledronate (0.1 mg/kg) or MPMBP (1.2 or 6.0 mg/kg) was injected subcutaneously every three days either from the age of 3 to 18 days or from the age of 3 to 6 weeks. At the end of the experiments, bone and plasma samples were harvested and examined.
Results: The body weight of all rats increased normally in both the zoledronate- and MPMBP-treated groups compared to that in the saline-injected control rats. Bone morphometry analyses using X-ray micro-computed tomography showed that both bisphosphonates increased bone mass and density of the distal femur and proximal tibia; these findings were consistent with our previous findings. Plasma tartrate-resistant acid phosphatase levels decreased in both the zoledronate- and MPMBP-treated groups, whereas plasma bone alkaline phosphatase levels deceased in the zoledronate-treated group but did not change in the MPMBP-treated group compared to those in the controls. Moreover, the zoledronate-treated group showed a marked delay in tooth eruption, whereas the MPMBP-treated group showed eruption of all teeth at the appropriate developmental stage.
Conclusions: In conclusion, these results show that MPMBP has potent anabolic action on bones without adverse effects due to excessive inhibition of bone resorption and/or bone turnover, which limit the clinical use of bisphosphonates in children.