The Effect of Soaking Allograft in Bisphosphonate: A Pilot Dose-response Study

Abstract

Background Long-term survival of uncemented total joint replacements relies on osseointegration. With reduced bone stock impacted morselized allograft enhances early implant fixation but is subject to resorption. Purpose We therefore asked whether soaking morselized allograft in different concentrations of bisphosphonate before impaction would enhance fixation. Methods In each of 10 dogs, we implanted four unloaded titanium implants surrounded by a 2.5-mm gap into the proximal humerus, two implants in each humerus. The gap was filled with impacted morselized allograft soaked in saline or a low-, middle-, or high-dose bisphosphonate solution (0.005, 0.05, or 0.5 mg zoledronate/mL). At 4 weeks, the implants were evaluated by histomorphometric analysis and mechanical pushout test. Results The low dose of zoledronate increased new bone formation in the allograft but the high dose decreased new bone formation. The high dose of zoledronate resulted in the greatest inhibition of allograft resorption, whereas the low dose of zoledronate resulted in the lowest inhibition of allograft resorption. Implants surrounded allograft soaked in the low dose of zoledronate or saline had better fixation for all three mechanical parameters compared with implants surrounded by allograft soaked in the middle or high dose of zoledronate. Conclusions These data suggest bisphosphonate may enhance osseointegration of allografted implants and emphasize the need for preclinical testing of antiresorptive therapies.

Preclinical Evaluation of Zoledronate to Maintain Bone Allograft and Improve Implant Fixation in Revision Joint Replacement

“…However, despite preservation of the allograft, not all studies indicated a positive effect on mechanical implant fixation 11,12 . In an earlier dose-response study 13 , we found that zoledronate caused a dose-dependent inhibition of the resorption of bone allograft. At higher doses, bone formation was blocked, whereas at the lowest dose allograft resorption was delayed without impairing new bone formation.…”

“…The treatment may reduce allograft resorption and reduce the risk of mechanical implant failure. Several studies have indicated that bisphosphonate-treated bone allograft is not as readily resorbed as untreated bone allograft [6][7][8][9][10][11][12][13] . However, despite preservation of the allograft, not all studies indicated a positive effect on mechanical implant fixation 11,12 .…”

“…We chose the lowest zoledronate dose used in the doseresponse study by Jakobsen et al 13 , and the allograft was rinsed thoroughly after soaking in the zoledronate solution. Our results are in agreement with the results from that dose-response study.…”

Does locally delivered Zoledronate influence peri-implant bone formation? – Spatio-temporal monitoring of bone remodeling in vivo

“…Several in vivo studies have shown that a local delivery of BPs can enhance peri-implant bone density [16,17], implant fixation [18e22], and the repair of bony defects [23,24] in animal models and humans. Furthermore BPs have been shown to preserve bone allografts [25,26] as well as bone sites affected by osteonecrosis [27].…”

Osteoinductivity of Demineralized Bone Matrix Is Independent of Donor Bisphosphonate Use

“…Bisphosphonates do affect the biosynthetic characteristics of osteoblasts 21,22 , suggesting that there may be alterations in the extracellular matrix as a consequence of use. Recently, it has been found that the addition of bisphosphonates to implanted allograft bone affects the rate of allograft resorption and can affect the success of implants used with allograft 23,24 . Demineralized bone matrix is commonly used as a bone graft substitute, either alone or to supplement an osteoconductive material, because of its osteoinductive properties.…”