Histologic and Histomorphometric Analysis of the Effects of Bisphosphonate and Parathyroid Hormone with Bone Graft on Bone Healing and Formation in Rabbit Models.

Abstract

Introduction: The standard method to accelerate healing of large bone defects involves using bone grafts alone or with biomaterials. Given the effects of bisphosphonates and parathyroid hormone (PTH) on bone remodeling, and the limited and contradictory studies available, this study aimed to evaluate the histologic and histomorphometric effects of combining bisphosphonate (zoledronic acid) and PTH (teriparatide) with bone grafts on bone healing and formation in rabbit models.

Methods: Bilateral defects were created in the tibias 35 New Zealand white rabbits, divided into four groups, including negative control (no treatment) (n=5), positive control (bone powder) (n=10), intervention 1 (zoledronic acid+bone powder) (n=10), and intervention 2 (teriparatide+bone powder) (n=10). In each of the groups, half of the rabbits were euthanized in the 8th week and the other half in the 16th week after surgery, and their tibia bones were removed for histologic and histomorphometric evaluations. The outcomes were new bone formation, remaining bone graft percentage, foreign body reaction, and inflammation levels.

Results: The highest percentage of new bone formation in the 8th week was observed in the intervention 2 group; in the 16th week, it was observed in the negative control group. However, the difference between the groups was not significant neither in the 8th week nor in the 16th week (P>0.05). The percentage of remaining bone graft in the intervention 1 group in the 8th and 16th week was significantly higher than in other groups (P<0.05). In week 8, the amount of inflammation in the intervention 1 group was non-significantly higher than in the intervention 2 group (P>0.05), and in week 16, the amount of inflammation in the intervention group 1 was significantly higher than in the other two groups (P<0.05). The highest frequency of foreign body reaction in the 8th and 16th weeks was related to the intervention 1 group (P<0.05).

Conclusion: Overall, teriparatide showed favorable outcomes. Teriparatide and bisphosphonate exhibited distinct and potentially complementary effects. Teriparatide promoted new bone formation and resorption, while bisphosphonates reduced bone graft resorption and caused inflammation and foreign body reactions. Further large-scale animal studies on teriparatide and bisphosphonate are recommended. These findings suggest time-dependent effects, with teriparatide potentially accelerating early healing and bisphosphonates prolonging graft persistence, though larger studies are necessary to confirm non-significant trends.