PAPER 067: SKELETAL DISTRIBUTION OF 14C-LABELED BISPHOSPHONATE AFTER LOCAL ELUTION FROM POROUS IMPLANTS

Abstract

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.