title: Bone formation in a carbonate-substituted hydroxyapatite implant is inhibited by zoledronate: the importance of bioresorption to osteoconduction.
abstract: Carbonate-substituted hydroxyapatite (CHA) is more osteoconductive and more resorbable than hydroxyapatite (HA), but the underlying mode of its action is unclear. We hypothesised that increased resorption of the ceramic by osteoclasts might subsequently upregulate osteoblasts by a coupling mechanism, and sought to test this in a large animal model. Defects were created in both the lateral femoral condyles of 12 adult sheep. Six were implanted with CHA granules bilaterally, and six with HA. Six of the animals in each group received the bisphosphonate zoledronate (0.05 mg/kg), which inhibits the function of osteoclasts, intra-operatively. After six weeks bony ingrowth was greater in the CHA implants than in HA, but not in the animals given zoledronate. Functional osteoclasts are necessary for the enhanced osteoconduction seen in CHA compared with HA.
authors.affiliation: Orthopaedic Research Unit, University of Cambridge, Addenbrookes Hospital, Cambridge, England. gmspence59@yahoo.co.uk
authors.forename: G
authors.initials: G
authors.lastname: Spence
authors.forename: S
authors.initials: S
authors.lastname: Phillips
authors.forename: C
authors.initials: C
authors.lastname: Campion
authors.forename: R
authors.initials: R
authors.lastname: Brooks
authors.forename: N
authors.initials: N
authors.lastname: Rushton
mesh_terms: D000818:Animals; D001861:Bone Regeneration / Q000187:drug effects / Q000502:physiology; D018786:Bone Substitutes / Q000737:chemistry* / Q000493:pharmacokinetics; D002254:Carbonates / Q000737:chemistry*; D002516:Ceramics / Q000737:chemistry / Q000493:pharmacokinetics; D017886:Durapatite / Q000737:chemistry* / Q000493:pharmacokinetics; D005264:Femoral Fractures / Q000601:surgery; D005269:Femur / Q000503:physiopathology / Q000601:surgery; D017102:Fracture Healing / Q000502:physiology; D020007:Implants, Experimental; D008422:Materials Testing / Q000379:methods; D016348:Osseointegration / Q000187:drug effects / Q000502:physiology; D010012:Osteogenesis / Q000187:drug effects* / Q000502:physiology; D012756:Sheep
chemical_list: D018786:Bone Substitutes; D002254:Carbonates; D017886:Durapatite