The variability in the results of the studies included in this review, may not only relate to SRAN dose, but may somehow relate to differences in the time-period after ovariectomy, before the animals were included in the study, which differed greatly among studies (from 4 to 12 weeks). Although it is already defined in the literature that initial osteoporosis features appear already at 4 weeks after ovariectomy [58], in not a single study included in this review, were the osteoporotic conditions after ovariectomy confirmed by a specific test [31,32,33]. Thus, comparison of animals 4 and 12 weeks after ovariectomy in terms of bone architecture characteristics may not be considered optimal, since they represent diverse stages of osteoporotic state [58]. In the same context, in some studies, SRAN treatment started the same day of implant installation [30,31,32,33], while in other studies, treatment started 7 days after implantation [31]; SRAN treatment duration also varied much from among studies (from 4 to 12 weeks). Considering the fact that implant osseointegration in rats is completed within maximum 8 weeks after installation [59] and the fact that it is not yet known for how long should SRAN be used before it exerts a measureable effect on bone architecture, differences in the time-point of SRAN treatment start and its duration may have contributed to the variability in the results. Finally, differences in the evaluation methods used in the various studies, ranging from the gold-standard for osseointegration assessment, i.e., histomorphometry, to diverse biomechanical tests, and microtomography that has the inherent drawback of metal artifacts hampering osseointegration evaluation [60], may have also contributed to the observed variability in the results.

According to SYRCLE’s tool for assessing risk of bias [28], most studies were unclear regarding relevant steps in the selection, performance, detection, and attrition characteristics. On the other hand, there was a low risk for bias related to outcome reporting, so that the conclusions were often and straight-forward related towards the listed aims. Finally, a high risk for other biases, mostly related to inconsistency when defining and reporting the SRAN posology was seen in all included studies, something highly relevant, since it could directly reflect on the results and interfere in the reproducibility of the studies.