Early tissue responses to zoledronate, locally delivered by bone screw, into a compromised cancellous bone site: a pilot study.

BACKGROUND: In fracture treatment, adequate fixation of implants is crucial to long-term clinical performance. Bisphosphonates (BP), potent inhibitors of osteoclastic bone resorption, are known to increase peri-implant bone mass and accelerate primary fixation. However, adverse effects are associated with systemic use of BPs. Thus, Zoledronic acid (ZOL) a potent BP was loaded on bone screws and evaluated in a local delivery model. Whilst mid- to long-term effects are already reported, early cellular events occurring at the implant/bone interface are not well described. The present study investigated early tissue responses to ZOL locally delivered, by bone screw, into a compromised cancellous bone site. METHODS: ZOL was immobilized on fibrinogen coated titanium screws. Using a bilateral approach, ZOL loaded test and non-loaded control screws were implanted into femoral condyle bone defects, created by an overdrilling technique. Histological analyses of the local tissue effects such as new bone formation and osteointegration were performed at days 1, 5 and 10. RESULTS: Histological evaluation of the five day ZOL group, demonstrated a higher osseous differentiation trend. At ten days an early influx of mesenchymal and osteoprogenitor cells was seen and a higher level of cellular proliferation and differentiation (p < 5%). In the ZOL group bone-to-screw contact and bone volume values within the defect tended to increase. Local drug release did not induce any adverse cellular effects. CONCLUSION: This study indicates that local ZOL delivery into a compromised cancellous bone site actively supports peri-implant osteogenesis, positively affecting mesenchymal cells, at earlier time points than previously reported in the literature.

In vivo assessment of local effects after application of bone screws delivering bisphosphonates into a compromised cancellous bone site.

BACKGROUND: The primary stability of cancellous screw is difficult to obtain in bone of compromised quality and failure of screw fixation is common. To overcome this problem, it is proposed to locally deliver bisphosphonate from the screw. An in vivo validation of the increase in fixation of the cancellous screw is then needed in compromised bone. METHODS: In this study, we used an overdrilling procedure, which enables consistent modeling of reduced screw stability comparable to compromised cancellous bone. Forty eight adult NZW rabbits were used in this study and all animals underwent bilateral femur implantation. One leg was implanted with the screw containing the bisphosphonate (biocoated group) while the other was used as control (control group) with the screw only. Mechanical testing and micro-CT imaging were used to assess the effect of local drug delivery of Zoledronate on screws fixation at 5 time points. FINDINGS: At the early time points (1, 5, and 10 days), no significant difference could be seen between the biocoated and control groups. At 6 weeks, the bone volume fraction was significantly higher in the trabecular region of the biocoated group. However, this increase did not have a significant effect on the pull-out force. At the last time point, 11 weeks, both the bone volume fraction and the pull-out force were significantly higher in the biocoated group. INTERPRETATION: The results of this study suggest that, in compromised bone, local delivery of bisphosphonate enhances the stability of bone screws.