Zoledronate reduces unwanted bone resorption in intercalary bone allografts

Abstract

Bone allografts are often hampered by graft incorporation and poor host bone formation. Bisphosphonates, synthetic pyrophosphate analogs, have shown promise in inhibiting bone resorption in human and animal trials. Some in vitro studies have suggested that high dose bisphosphonate may also inhibit bone formation, leading to our hypothesis that an ideal dose of bisphosphonate in allografts could protect allografts from resorption. We transplanted intercalary allografts in to the segmental defect of the rat femurs after soaking each allograft in zoledronate solution (30 µM) and then analysed bone density of the allografts six to 12 weeks after transplantation. At six and 12 weeks, the bone mineral density was higher in the experimental group compared with the control group. Qualitative radiographic and histological analysis also revealed more allograft resorption in the control group than in the zoledronatetreated group. Our data indicate that pharmacological modification of intercalary allografts with zoledronate solution can decrease osteoclast-mediated allograft resorption.

Locally enhanced early bone formation of zoledronic acid incorporated into a bone cement plug in vivo

“…demonstrated that ZOL reduces unwanted bone resorption in intercalary bone allografts. The optimal soaking concentration for the allografts was 0.03 mmol ZOL with a significant increase in bone‐mass density . Tanzer et al .…”

“…The mechanism by which bisphosphonates work in combination with calcium systems in vivo is briefly described as follows: Seo et al . demonstrated that the potent N‐containing bisphosphonate ZOL reduces unwanted bone resorption processes . ZOL inhibits osteoclastic activity and regulates cell proliferation, differentiation and gene expression in osteoblasts due to a stimulation of bone formation .…”

The effects of topical application of bisphosphonates on replanted rat molars

“…Among BPs currently in use, zoledronate, which is most frequently administered intravenously, has the highest binding affinity with Hydroxyapatite. Moreover, zoledronate is characterized by the most rapid onset and longest lasting action of all BPs and as such constitutes a promising candidate for use in dental applications (23–25). Under the assumption that zoledronate pharmacological effects on the inflammatory inhibition are superior to etidronate and the alendronate, we tested the treatment effects by setting the control group as the negative control and alendronate group as the positive control.…”

Physiologic load-bearing characteristics of autografts, allografts, and polymer-based scaffolds in a critical sized segmental defect of long bone: an experimental study

“…To test our hypothesis, we used a rat femoral segmental defect model, which has been used previously to test the effects of various materials and agents on bone growth. [9][10][11][12][13][14] We created a 5 mm femoral defect, replaced the defect with appropriate grafts, and repaired the construct using an intramedullary K-wire. Segmental defects of 5 mm in the rat femurs have been shown to result consistently in nonunions, both radiographically and clinically.…”