title: Local ZnCl2 accelerates fracture healing.
abstract: This study evaluated the effect of local zinc chloride (ZnCl2 ), an insulin mimetic agent, upon the early and late parameters of fracture healing in rats using a standard femur fracture model. Mechanical testing, radiographic scoring, histomorphometry, qualitative histological scoring, PCNA immunohistochemistry, and local growth factor analysis were performed. Fractures treated with local ZnCl2 possessed significantly increased mechanical properties compared to controls at 4 weeks post fracture. The radiographic scoring analysis showed increased cortical bridging at 4 weeks in the 1.0 (p=0.0015) and 3.0 (p<0.0001) mg/kg ZnCl2 treated groups. Histomorphometry of the fracture callus at day 7 showed 177% increase (p=0.036) in percent cartilage and 133% increase (p=0.002) in percent mineralized tissue with local ZnCl2 treatment compared to controls. Qualitative histological scoring showed a 2.1× higher value at day 7 in the ZnCl2 treated group compared to control (p = 0.004). Cell proliferation and growth factors, VEGF and IGF-I, within fracture calluses treated with local ZnCl2 were increased at day 7. The results suggest local administration of ZnCl2 increases cell proliferation, causing increased growth factor production which yields improved chondrogenesis and endochondral ossification. Ultimately, these events lead to accelerated fracture healing as early as 4 weeks post fracture.
authors.affiliation: Rutgers New Jersey Medical School, Department of Orthopaedics, 90 Bergen Street, Suite 7300, Newark, New Jersey, 07103.
authors.forename: Aaron
authors.initials: A
authors.lastname: Wey
authors.forename: Catherine
authors.initials: C
authors.lastname: Cunningham
authors.forename: Jeremy
authors.initials: J
authors.lastname: Hreha
authors.forename: Eric
authors.initials: E
authors.lastname: Breitbart
authors.forename: Jessica
authors.initials: J
authors.lastname: Cottrell
authors.forename: Joseph
authors.initials: J
authors.lastname: Ippolito
authors.forename: Devin
authors.initials: D
authors.lastname: Clark
authors.forename: Hsuan-Ni
authors.initials: HN
authors.lastname: Lin
authors.forename: Joseph
authors.initials: J
authors.lastname: Benevenia
authors.forename: J Patrick
authors.initials: JP
authors.lastname: O'Connor
authors.forename: Sheldon S
authors.initials: SS
authors.lastname: Lin
authors.forename: David N
authors.initials: DN
authors.lastname: Paglia
mesh_terms: D000818:Animals; D002146:Bony Callus / Q000187:drug effects*; D049109:Cell Proliferation; D002712:Chlorides / Q000627:therapeutic use*; D020219:Chondrogenesis; D005264:Femoral Fractures / Q000188:drug therapy* / Q000473:pathology; D005269:Femur / Q000187:drug effects; D017102:Fracture Healing / Q000187:drug effects*; D007334:Insulin-Like Growth Factor I / Q000096:biosynthesis; D008297:Male; D018809:Proliferating Cell Nuclear Antigen / Q000096:biosynthesis; D051381:Rats; D011913:Rats, Inbred BB; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis; D017967:Zinc Compounds / Q000627:therapeutic use*
chemical_list: D002712:Chlorides; D018809:Proliferating Cell Nuclear Antigen; D042461:Vascular Endothelial Growth Factor A; D017967:Zinc Compounds; C548904:insulin-like growth factor-1, rat; C467498:vascular endothelial growth factor A, rat; D007334:Insulin-Like Growth Factor I; C016837:zinc chloride
keywords: bone healing; fracture healing; insulin mimetic; rat; zinc chloride