title: Role of parathyroid hormone in the mechanosensitivity of fracture healing.
abstract: The mechanical environment at a fracture site can influence the course of healing. Intermittent parathyroid hormone (PTH) has been shown to accelerate fracture healing. Intact bone models show that mechanical loading and PTH have a synergistic beneficial effect on osteogenesis. We hypothesized that PTH and mechanical loading would have a similar synergistic effect on fracture healing. Eighty mice underwent surgical osteotomy and intramedullary nailing of the tibia. The mice were divided into four groups: one underwent daily loading, one received daily subcutaneous PTH injections (30 microg/kg/day), one received both loading and PTH, and a control group received sham loading and vehicle injection. Daily loading was applied to the ends of the tibia with an external loading device for 2 weeks. Fracture healing was assessed by microcomputed tomography, histology, and biomechanical testing. The group with both loading and PTH had increased osteoblast and osteoclast activity and was the only group with a significantly larger callus mineral density and bone volume fraction. The PTH only group had significantly more osteoid in the callus compared to the control group, indicating enhanced early osteoblast activity. This group also had a significantly higher bone mineral content and total bone volume compared to controls. The group that received loading as the only intervention had significantly greater osteoclast activity versus controls. The contribution of loading and PTH administration to the fracture healing cascade indicates a synergistic effect. This finding may be of potential clinical utility when weight bearing is utilized to stimulate lower extremity fracture healing.
authors.affiliation: Hospital for Special Surgery, 535 East 70th Street, New York, New York 10021, USA. gardnerm@hss.edu
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Gardner
authors.forename: Marjolein C H
authors.initials: MC
authors.lastname: van der Meulen
authors.forename: Joshua
authors.initials: J
authors.lastname: Carson
authors.forename: Jonathan
authors.initials: J
authors.lastname: Zelken
authors.forename: Benjamin F
authors.initials: BF
authors.lastname: Ricciardi
authors.forename: Timothy M
authors.initials: TM
authors.lastname: Wright
authors.forename: Joseph M
authors.initials: JM
authors.lastname: Lane
authors.forename: Mathias P
authors.initials: MP
authors.lastname: Bostrom
mesh_terms: D000818:Animals; D015519:Bone Density / Q000187:drug effects / Q000502:physiology; D019245:Compressive Strength / Q000187:drug effects / Q000502:physiology; D004195:Disease Models, Animal; D004334:Drug Administration Schedule; D017102:Fracture Healing / Q000187:drug effects* / Q000502:physiology; D007279:Injections, Subcutaneous; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010027:Osteotomy; D010281:Parathyroid Hormone / Q000008:administration & dosage / Q000494:pharmacology*; D013314:Stress, Mechanical; D013977:Tibia / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D013978:Tibial Fractures / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000378:metabolism; D014057:Tomography, X-Ray Computed; D016474:Weight-Bearing / Q000502:physiology
chemical_list: D010281:Parathyroid Hormone