title: Early tissue responses to zoledronate, locally delivered by bone screw, into a compromised cancellous bone site: a pilot study.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Stryker Osteosynthesis, Selzach, Switzerland. joergarnoldi@sunrise.ch.
authors.forename: Joerg
authors.initials: J
authors.lastname: Arnoldi
authors.forename: Antoine
authors.initials: A
authors.lastname: Alves
authors.forename: Philip
authors.initials: P
authors.lastname: Procter
mesh_terms: D000818:Animals; D001862:Bone Resorption / Q000517:prevention & control*; D001863:Bone Screws; D020099:Coated Materials, Biocompatible; D004164:Diphosphonates / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D004353:Drug Evaluation, Preclinical; D005122:Exudates and Transudates; D005269:Femur / Q000187:drug effects* / Q000473:pathology; D005337:Fibrin / Q000032:analysis; D005340:Fibrinogen; D005355:Fibrosis; D007093:Imidazoles / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D020007:Implants, Experimental; D008264:Macrophages / Q000473:pathology; D008297:Male; D008648:Mesoderm / Q000473:pathology; D016348:Osseointegration; D010010:Osteoclasts / Q000187:drug effects; D010865:Pilot Projects; D011817:Rabbits; D014025:Titanium; D000077211:Zoledronic Acid
chemical_list: D020099:Coated Materials, Biocompatible; D004164:Diphosphonates; D007093:Imidazoles; D000077211:Zoledronic Acid; D005337:Fibrin; D005340:Fibrinogen; D014025:Titanium