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.

Purpose: The bisphosphonate Zoledronic acid (ZA) is effective for increasing net bone formation within and around implants when directly eluted from implants. The extent to which this occurs or whether ZA is more widely distributed through diffusion into the circulation is unknown. The purpose of this study was to utilize 14C-labeled ZA to quantify the localization and skeletal distribution of ZA in a canine intramedullary implant model.

Method: A solution of 100μg 14C-labeled ZA was evenly distributed onto each implant surface of three hydroxyapatite coated porous tantalum (Trabecular Metal^™, Zimmer Inc) implants measuring 5 mm in diameter and 50 mm in length. The implants were inserted within the left femoral intramedullary canal of an adult mongrel dog and left in situ for 6 weeks. The 3 femora with implants and all the other long bones were harvested, dried, pulverized into a fine powder and disolved in HCl. This solution was then placed in a scintillation cocktail (Ultima Gold AB, Perkin Elmer USA) and analyzed with a Packard Tri-Carb 2100TR liquid scintillator spectrometer. Data were analyzed with student’s t tests and nested analyses of variance with p=0.05.

Results: Very high amounts of ZA were present within the bone samples immediately adjacent to the implants – range 243 – 1487 ng ZA/g of bone, mean of 800 ng ZA/g. By 1 cm proximal or distal to the implant, the values diminished by up to an order of magnitude. All other bone samples contained very low amounts of 14C, (range, 0.8 – 22.6 ng ZA/g; mean 6.5 ng ZA/g), indicating diffusion of ZA into the circulation and a level of systemic distribution. This is about 11-fold less in magnitude (p< 0.0001).

Conclusion: Local elution of ZA directly from an implant results in half of the ZA being distributed locally in the femur with the rest being distributed throughout the skeleton, at levels that are much less than the therapeutic dose required to appreciably affect bone remodeling or cause complications. postoperative time periods.