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

Abstract

a b s t r a c tBisphosphonates are known for their strong inhibitory effect on bone resorption. Their influence on bone formation however is less clear. In this study we investigated the spatio-temporal effect of locally delivered Zoledronate on peri-implant bone formation and resorption in an ovariectomized rat femoral model. A cross-linked hyaluronic acid hydrogel was loaded with the drug and applied bilaterally in predrilled holes before inserting polymer screws. Static and dynamic bone parameters were analyzed based on in vivo microCT scans performed first weekly and then biweekly. The results showed that the locally released Zoledronate boosted bone formation rate up to 100% during the first 17 days after implantation and reduced the bone resorption rate up to 1000% later on. This shift in bone remodeling resulted in an increase in bone volume fraction (BV/TV) by 300% close to the screw and 100% further away. The double effect on bone formation and resorption indicates a great potential of Zoledronateloaded hydrogel for enhancement of peri-implant bone volume which is directly linked to improved implant fixation.

Time course of bone screw fixation following a local delivery of Zoledronate in a rat femoral model – A micro-finite element analysis

“…The increase in force at yield and pullout as well as in stiffness for the Zol-Gel group was also caused to a high extent by the periosteal callus formation and resulting thickening of the cortex which was observed in this group around the screw head (Kettenberger et al, 2014). The newly formed trabecular bone seems to play a less significant role for the load transfer.…”

“…This might be a disadvantage in the current study as the bone trauma caused by the insertion of an implant is known to cause a rapid formation of woven bone in direct proximity of the implant (Marco et al, 2005). We recently showed that this early peri-implant bone formation is even enhanced by a fast local delivery of Zoledronate (Kettenberger et al, 2014). Studies have also shown that the BP can delay the remodeling of the newly formed woven bone to lamellar bone (McDonald et al, 2008), however the intrinsic mechanical properties of healing bone should not be affected by the BP (Amanat et al, 2008).…”

“…The in vivo microCT data, that provided the basis for the microFE models, were obtained from an animal study published earlier by our group (Kettenberger et al, 2014). Since the miniature polymer screws used in the in vivo study were not suitable for biomechanical pullout tests, we performed a complementary cadaver study with aluminum screws on similar bone specimens and with similar screw geometry.…”

“…Both femurs of all animals were scanned with a special in vivo microCT for small rodents (Skyscan 1076, Bruker microCT, Kontich, Belgium) at day 3, 10, 17, 31, 45, and 58 after screw implantation. The used scanning parameters were published earlier (Kettenberger et al, 2014). Hydroxyapatite-polymer phantoms (diameter 4 mm, Bruker microCT, Kontich, Belgium) with known bone mineral density served as references for the microCT calibration.…”

“…The reconstruction of the projection images was done with NRecon and GPURecon Server (Bruker microCT, Kontich, Belgium) following a protocol that was published earlier (Kettenberger et al, 2014). Image processing after reconstruction was done with CTan (Bruker microCT, Kontich, Belgium) and Amira s (FEI Visualization Sciences Group, Burlington, USA).…”