Effects of local alendronate administration on bone defect healing. Histomorphometric and radiological evaluation in a rabbit model

Abstract

Purpose: To performed a histomorphometric and radiological study to evaluate the effects of alendronate sodium administered locally in mandibular bone defects created in rabbits. Methods: Two circular defects 5 mm in diameter were created bilaterally in the mandibular corpus of 20 New Zealand rabbits (i.e., four defects per animal). Each defect received one of four treatments: no treatment (EC group), alendronate irrigation (AL group), autogenous bone grafting (AG group), or alendronate irrigation with autogenous bone grafting (AL+AG group). Histomorphometric and radiological assessments were conducted at 4 and 8 weeks after surgery. Results: Between-group comparisons of the new bone area, the value of the AL+AG group was significantly lower thanthe remaining three groups at 4 weeks postoperatively. In all groups, the new bone area was significantly larger at 8 weeks than at 4 weeks. The residual graft area at 4 and 8 weeks was significantly higher in the AL+AG group than in the AG group, although it was significantly smaller at 8 weeks than at 4 weeks in both these groups. Conclusion: The use of alendronate sodium in conjunction with autogenous bone grafting improves the osteoconductive properties of the graft, enhances graft retention in the defect, and improves ossification.

Effect of Local Application of Alendronate and Parathyroid Hormone on Craniofacial Bone Repair - a Preliminary Study

“…Agholme and Aspenberg (29) reported that soaking bone grafts in alendronate solution (2 mg/mL diluted in saline) before implantation can prevent their resorption and increase local bone density in rats and humans. Ozer et al in 2017 (30) also founded that the residual graft area 4 and 8 weeks postoperatively, was significantly higher when associated with alendronate irrigation during autogenous bone grafting in mandibular circular defects. This finding is in contrast with that of the present study, in which the histological analysis revealed that group A1, which consisted of treatment with graft immersion in alendronate solution, presented lower bone relative area and fewer particles undergoing osseointegration than the control group.…”

“…However, the best route of administration for these drugs to accelerate bone repair has not been determined. Sodium alendronate and PTH can be administered via the same systemic or local routes (7,(10)(11)(12)(13)18,19). Systemic administration of these drugs, either orally or by injection, may not be easily accepted by the patients being subjected to bone grafting procedures.…”

“…On the other hand, bisphosphonates are proven to be effective in inhibiting bone loss due to their ability of decreasing osteoclastic activity, but are not effective in improving bone density in the bone formation phase (35). Some authors, to further promote bone healing, have combined bisphosphonates with other substances, such as collagen membrane and different graft materials, achieving better bone repair outcomes (30,36). PTH acts by stimulating osteogenesis (2), and is considered the only therapeutic agent recommended for bone formation (37).…”

“…There are a few studies associating systemic application of alendronate, either intraperitoneally (10,11) or subcutaneously (12) or by the topical route, either by irrigation (13) or by local application (7), with bone repair in cranial defects. Due to a certain similarity between alendronate and parathyroid hormone (PTH) with regard to the potential of accelerating bone replenishment, some authors have been working on comparing these drugs in the same study (14,15).…”

Effects of alendronate in bone repair: A study in rat femur fractures treated with plates and screws

“…We chose to use the human-based dose, which corresponds to 1 mg/kg, as well as a dose triple that. Previous research has already shown that reduced doses of alendronate may improve osteoblast differentiation and bone matrix formation (25,32), although the literature has not expounded on whether the ideal dosage of the drug can bene t bone repair. A greater dosage of ALN has been proven to be more effective in qualitative microtomographic analysis of bone repair.…”