OP-1 augments glucocorticoid-inhibited fracture healing in a rat fracture model.
Glucocorticoids inhibit bone remodeling and fracture healing. We sought to determine whether osteogenic protein 1 (OP-1) can overcome this inhibition in a closed fracture model in the rat. Time-released prednisolone or placebo pellets were implanted subcutaneously; closed femoral fractures were created 2 weeks later in rats. Fractures received sham, OP-1 and collagen, or collagen-only implants. Femurs were harvested at 3, 10, 21, 28, and 42 days postfracture. Fractures were examined radiographically for amount of hard callus; mechanically for torque and stiffness (also expressed as a percentage of the contralateral intact femur); and histomorphometrically for amount of cartilaginous and noncartilaginous soft callus, hard callus, and total callus. Glucocorticoid administration inhibited fracture healing. The application of a devitalized Type I collagen matrix mitigated the inhibitory effects of prednisolone on fracture healing However, further increases in indices of fracture healing were observed when OP-1 was added to the collagen matrix compared with collagen alone. OP-1 and collagen was more effective than collagen alone.
Gilley
Robert S
RS
Department of Small Animal Clinical Sciences, College of Veterinary Medicine, University of Minnesota, St Paul, MN, USA. rsgilley@vet.upenn.edu
Wallace
Larry J
LJ
Bourgeault
Craig A
CA
Kidder
Louis S
LS
Bechtold
Joan E
JE
D000818:Animals; D001696:Biomechanical Phenomena; D055419:Bone Morphogenetic Protein 7 / Q000008:administration & dosage*; D016723:Bone Remodeling / Q000187:drug effects*; D002146:Bony Callus / Q000187:drug effects / Q000503:physiopathology; D024042:Collagen Type I; D004195:Disease Models, Animal; D004337:Drug Carriers; D004343:Drug Implants; D005264:Femoral Fractures / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000503:physiopathology; D005269:Femur / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000503:physiopathology; D017102:Fracture Healing / Q000187:drug effects*; D005938:Glucocorticoids / Q000008:administration & dosage*; D008297:Male; D011239:Prednisolone / Q000008:administration & dosage*; D011859:Radiography; D051381:Rats; D013997:Time Factors; D019415:Torque
D055419:Bone Morphogenetic Protein 7; D024042:Collagen Type I; D004337:Drug Carriers; D004343:Drug Implants; D005938:Glucocorticoids; D011239:Prednisolone