Bone Regeneration Using Antiosteoporotic Drugs in Adjunction with Bone Grafting: A Meta-Analysis.

The aim of this review was to systematically assess bone regeneration by using antiosteoporotic drugs in adjunction with bone grafting compared with controls (bone grafting without the administration of antiosteoporotic drugs). The review also evaluated statistical differences in the effect between systemic and local routes of drugs. Also, the effect of type of drugs (anticatabolic vs. anabolic) was subevaluated. PubMed and EMBASE (via OvidSP) resulted in inclusion of 60 animal studies. The studies were assessed for reporting quality and risk of bias. Outcome data from selected studies were categorized as either experimental (bone grafting with the administration of antiosteoporotic drugs) or control. Meta-analysis of selected studies was done for these outcomes: histomorphometrical bone area (BA%) and micro-CT bone volume (BV%). In this review, several animal models (52 healthy, 6 osteoporotic, and 2 both conditions) were subjected to examine the effect of antiosteoporotic drugs on bone grafting, with a predominant use of rodent species. Assessment indicates poor reporting quality and unclear risk of bias in the majority of studies. Random-effects meta-analysis revealed a significant increase in overall BA% (mean difference [MD]: 2.6, confidence interval [CI]: 2.25 to 2.92) and BV% (MD: 0.12, CI: 0.05 to 0.19) due to osteoporotic drug treatment compared with controls. For subgroups, both routes of antiosteoporotic drug administration showed similar effects on BA%. In contrast, systemic antiosteoporotic drug administration led to significantly higher BV% (MD: 6.75, CI: 5.30 to 8.19) compared with local administration (MD: 0.02, CI: -0.03 to 0.08). Further, administration of anabolic drugs significantly increased BA% (MD: 5.75, CI: 4.62 to 6.87) compared with anticatabolic drugs (MD: 1.86, CI: 1.47 to 2.26). In conclusion, both histomorphometrical and micro-CT scan analysis indicated an overall effect of using the antiosteoporotic drugs toward bone regeneration in adjunction with grafting. However, not all studies showed a positive effect and the present results need to be applied with care, as the included papers showed experimental heterogeneity for animal models. Further (pre)clinical research is warranted to explore whether drug-based strategies can be an effective adjunctive with bone grafting. Impact Statement The aim of this meta-analysis was to assess whether antiosteoporotic drugs can promote bone regeneration in adjunction with bone grafting by using preclinical animal models. Although the majority of included studies indicated poor reporting quality and unclear risk of bias, an overall positive effect of the antiosteoporotic drugs toward bone regeneration related to bone grafts can be highlighted.