Glucocorticoid attenuates the anabolic effects of parathyroid hormone on fracture repair.
Long-term use of glucocorticoid (GC) not only reduces bone mass and strength, which leads to a greater risk of fracture, but also hinders fracture repair. In this study, we produced open fractures in GC-treated mice and investigated the effects of human parathyroid hormone 1-34 (hPTH) on fracture repair. Swiss-Webster mice were randomly divided into five groups. Three groups of GC-treated mice were given prednisolone, which was slowly released from subcutaneously implanted pellets at the rate of 1.4 mg/kg/day. Placebo pellets were implanted into the animals in two placebo groups. Three weeks later, osteotomies at the midshaft femora were performed and intramedullary pins were inserted to stabilize the fracture site under general anesthesia. Following fracture surgery, three GC groups were treated subcutaneously with vehicle, PTH at a low dose (40 ug/kg/day), and PTH at a high dose (80 ug/kg/day), respectively. Two placebo groups were given vehicle and PTH at a dose of 40 ug/kg/day, respectively. Radiographs, dual-energy X-ray absorptiometry, and mechanical testing (four-point bending) were used to evaluate fracture repair at 4 weeks after fracture surgery. Callus development, endochondral ossification, and recovery of mechanical strength at the fracture sites in GC animals treated with vehicle were significantly suppressed compared to placebo animals. Normally, PTH accelerates fracture repair. In GC-treated mice, PTH fails to improve endochondral ossification and mechanical properties compared to vehicle treatment, suggesting that the anabolic effect of PTH on fracture healing can be attenuated by GC administration in mice.
Doyon
Anthony R
AR
Department of Biology, Indiana University-Purdue University Inidanapolis, 723 West Michigan Street, SL 306, Indianapolis, IN 46202, USA.
Ferries
Ian K
IK
Li
Jiliang
J
D015502:Absorptiometry, Photon; D000818:Animals; D001858:Bone Nails; D002146:Bony Callus / Q000000981:diagnostic imaging / Q000187:drug effects; D018483:Diaphyses / Q000000981:diagnostic imaging / Q000187:drug effects; D005269:Femur / Q000000981:diagnostic imaging / Q000187:drug effects; D017102:Fracture Healing / Q000187:drug effects; D005938:Glucocorticoids / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D051379:Mice; D010012:Osteogenesis / Q000187:drug effects; D010027:Osteotomy; D010281:Parathyroid Hormone / Q000008:administration & dosage* / Q000494:pharmacology* / Q000627:therapeutic use; D011239:Prednisolone / Q000494:pharmacology / Q000627:therapeutic use; D011897:Random Allocation; D014965:X-Rays
D005938:Glucocorticoids; C470125:PTH protein, human; D010281:Parathyroid Hormone; D011239:Prednisolone