PAPER 066: PERSISTENT NET BONE FORMATION AT ONE YEAR DUE TO LOCAL ELUTION OF ZOLEDRONIC ACID FROM POROUS TANTALUM IMPLANTS

Abstract

Purpose: Previous studies have shown the utility of the bisphosphonate zoledronic acid (ZA) by systemic administration and local delivery for enhancing local bone formation with porous implants. The purpose of this study was to quantify the long term effect of local delivery of ZA on bone growth within and around porous tantalum implants one year after surgery.

Method: Hydroxyapatite coated porous tantalum (Trabecular Metal^™, Zimmer Inc) implants measuring 9 mm in diameter and 90 mm in length were used in a canine bilateral femoral intramedullary model. Commercially pure ZA (Novartis Pharma) of either 0.05 mg or 0.20 mg ZA was applied to implants. Bilateral surgery was performed on 10 dogs – all 10 with a control implant on one side and 5 each with either a 0.05 mg or 0.20 mg ZA-dosed implant on the contralateral side. After one year, the femora were harvested and processed for undecalcified thin section histology and backscattered scanning electron microscopy. Statistical analysis was done using the student’s t tests and multiple two-level hierarchical models.

Results: The 160 histologic sections revealed that compared with controls, there was more intramedullary bone around implants dosed with both 0.05 mg ZA (+91%, p< 0.001) and 0.20 mg ZA (+115%, p< 0.001). Bone ingrowth was present in all sections and was more abundant within 1.5mm of the implant periphery. The 0.20 mg ZA dose resulted in more net intramedullary bone formation than the 0.05 mg dose (+41%, p< 0.006). The mean extent of bone ingrowth for implants dosed with 0.20 mg ZA was significantly greater than controls (+32%, p< 0.003) and also greater than for implants dosed with 0.05 mg ZA (+47% for the area within 1.5 mm of the periphery, p< 0.002).

Conclusion: This study demonstrated that the enhanced net bone formation that occurs due to local elution of ZA from porous implants was sustained out to 1 year after surgery. A notable dose response was also demonstrated. The peri-implant response was confined to within a few millimeters of the implant suggesting that ZA elution remains localized. This study supports the concept of using ZA-dosed implants for enhancing net bone formation within and around noncemented implants.