Response to Comment on Strontium Ranelate Reduces the Fracture Incidence in a Growing Mouse Model of Osteogenesis Imperfecta

Abstract

W e appreciate the kind words offered by Raggio and colleagues about our recent article.(1) Raggio and colleagues highlighted what they considered to be three problems with our discussion and reference. We address these three problems below.The first problem identified by Raggio and colleagues was in relation to our statement that "it is unclear whether treatment with bisphosphonates (BPs) can reduce the incidence of fracture and improve the clinical status in OI patients." In this sentence, we only emphasize the efficacy of BPs in the patients, not in the mice. In preclinical study, Raggio and colleagues found that BPs and RANK-FC could decrease fractures in the mouse model of OI. (2,3) In OI patients, however, the effects of BPs on the fracture reduction in several randomized control trials are still inconsistent. (4,5) The second issue raised by Raggio and colleagues was that we compared the treatment effect of strontium ranelate on fracture reduction to the brtl/þ mice but not to the results that they reported.(2) In fact, the reason why we cited the Brtl/þ mice (reference numbers 37 and 42 in the original study) was to explain some phenomena that we observed in our study, (6,7) not to compare the treatment effects on fracture. We do agree with Raggio and colleagues that the effect of strontium ranelate on fracture reduction in the oim/oim mice was comparable to what they reported (0.7 versus 0.9 fractures/mouse).(2) However, this is just an indirect comparison between these two drugs in two publications. Currently, a new study is underway in our laboratory to compare directly the effects of strontium ranelate and alendronate on fracture incidence in the oim/oim mice. We wish to share the works in future articles.In our study, we only chose the female mice for study. The first reason is that there may exist sex-dependent differences in response to pharmaceutical intervention in several mouse models of OI, which is what Raggio and colleagues mentioned. (8) Another reason why we did not include the male mice is that the male mice usually show more activity, sometimes even fighting and biting each other, which may cause fractures resulting from the bone fragility in this severe mouse model of OI. Because our primary goal was to evaluate the effect of strontium ranelate on the fracture reduction in OI, we thought that the male mice might not be suitable for the study.