title: Local insulin therapy affects fracture healing in a rat model.
abstract: A significant number of lower extremity fractures result in mal-union necessitating effective treatments to restore ambulation. Prior research in diabetic animal fracture models demonstrated improved healing following local insulin application to the fracture site and indicated that local insulin therapy can aid bone regeneration, at least within an insulin-dependent diabetic animal model. This study tested whether local insulin therapy could accelerate femur fracture repair in normal, non-diabetic rats. High (20 units) and low (10 units) doses of insulin were delivered in a calcium sulfate carrier which provided sustained release of the exogenous insulin for 7 days after fracture. Histomorphometry, radiographic scoring, and torsional mechanical testing were used to measure fracture healing. The fracture calluses from rats treated with high-dose insulin had significantly more cartilage than untreated rats after 7 and 14 days of healing. After 4 weeks of healing, femurs from rats treated with low-dose insulin had significantly higher radiographic scores and mechanical strength (p < 0.05), compared to the no treatment control groups. The results of this study suggest that locally delivered insulin is a potential therapeutic agent for treating bone fractures. Further studies are necessary, such as large animal proof of concepts, prior to the clinical use of insulin for bone fracture treatment.
authors.affiliation: Department of Orthopaedics, University of Medicine, Dentistry of New Jersey-New Jersey Medical School, 185 South Orange Avenue, 90 Bergen Street, Suite 7300, Newark, NJ 07103, USA.
authors.forename: Andrew G
authors.initials: AG
authors.lastname: Park
authors.forename: David N
authors.initials: DN
authors.lastname: Paglia
authors.forename: Loay
authors.initials: L
authors.lastname: Al-Zube
authors.forename: Jeremy
authors.initials: J
authors.lastname: Hreha
authors.forename: Swaroopa
authors.initials: S
authors.lastname: Vaidya
authors.forename: Eric
authors.initials: E
authors.lastname: Breitbart
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
mesh_terms: D000818:Animals; D001696:Biomechanical Phenomena / Q000187:drug effects / Q000502:physiology; D002133:Calcium Sulfate / Q000494:pharmacology*; D018483:Diaphyses / Q000000981:diagnostic imaging / Q000187:drug effects / Q000502:physiology; D004195:Disease Models, Animal; D004337:Drug Carriers / Q000494:pharmacology; D005260:Female; D005264:Femoral Fractures / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000503:physiopathology; D005269:Femur / Q000000981:diagnostic imaging / Q000187:drug effects / Q000502:physiology; D017102:Fracture Healing / Q000187:drug effects* / Q000502:physiology; D007004:Hypoglycemic Agents / Q000097:blood / Q000494:pharmacology; D015552:Injections, Intralesional; D061406:Insulin, Ultralente / Q000097:blood / Q000494:pharmacology*; D008297:Male; D011859:Radiography; D051381:Rats; D011913:Rats, Inbred BB; D017208:Rats, Wistar; D054159:Torsion, Mechanical
chemical_list: D004337:Drug Carriers; D007004:Hypoglycemic Agents; D061406:Insulin, Ultralente; D002133:Calcium Sulfate