title: Endogenous PTH deficiency impairs fracture healing and impedes the fracture-healing efficacy of exogenous PTH(1-34).
abstract: BACKGROUND
  Although the capacity of exogenous PTH1-34 to enhance the rate of bone repair is well established in animal models, our understanding of the mechanism(s) whereby PTH induces an anabolic response during skeletal repair remains limited. Furthermore it is unknown whether endogenous PTH is required for fracture healing and how the absence of endogenous PTH would influence the fracture-healing capacity of exogenous PTH.
  
  
  RESULTS
  Closed mid-diaphyseal femur fractures were created and stabilized with an intramedullary pin in 8-week-old wild-type and Pth null (Pth(-/-)) mice. Mice received daily injections of vehicle or of PTH1-34 (80 µg/kg) for 1-4 weeks post-fracture, and callus tissue properties were analyzed at 1, 2 and 4 weeks post-fracture. Cartilaginous callus areas were reduced at 1 week post-fracture, but were increased at 2 weeks post-fracture in vehicle-treated and PTH-treated Pth(-/-) mice compared to vehicle-treated and PTH-treated wild-type mice respectively. The mineralized callus areas, bony callus areas, osteoblast number and activity, osteoclast number and surface in callus tissues were all reduced in vehicle-treated and PTH-treated Pth(-/-) mice compared to vehicle-treated and PTH-treated wild-type mice, but were increased in PTH-treated wild-type and Pth(-/-) mice compared to vehicle-treated wild-type and Pth(-/-) mice.
  
  
  CONCLUSIONS
  Absence of endogenous PTH1-84 impedes bone fracture healing. Exogenous PTH1-34 can act in the absence of endogenous PTH but callus formation, including accelerated endochondral bone formation and callus remodeling as well as mechanical strength of the bone are greater when endogenous PTH is present. Results of this study suggest a complementary role for endogenous PTH1-84 and exogenous PTH1-34 in accelerating fracture healing.
authors.affiliation: Department of Orthopaedics, The First Affiliated Hospital, Nanjing Medical University, Nanjing, China.
authors.forename: Yongxin
authors.initials: Y
authors.lastname: Ren
authors.forename: Bo
authors.initials: B
authors.lastname: Liu
authors.forename: Yuxu
authors.initials: Y
authors.lastname: Feng
authors.forename: Lei
authors.initials: L
authors.lastname: Shu
authors.forename: Xiaojian
authors.initials: X
authors.lastname: Cao
authors.forename: Andrew
authors.initials: A
authors.lastname: Karaplis
authors.forename: David
authors.initials: D
authors.lastname: Goltzman
authors.forename: Dengshun
authors.initials: D
authors.lastname: Miao
mesh_terms: D000818:Animals; D015153:Blotting, Western; D001862:Bone Resorption / Q000188:drug therapy / Q000473:pathology; D002146:Bony Callus / Q000187:drug effects*; D017102:Fracture Healing / Q000187:drug effects*; D050723:Fractures, Bone / Q000188:drug therapy / Q000473:pathology*; D007124:Immunoenzyme Techniques; D051379:Mice; D018345:Mice, Knockout; D010281:Parathyroid Hormone / Q000494:pharmacology* / Q000502:physiology*; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014945:Wound Healing / Q000187:drug effects*
chemical_list: D010281:Parathyroid Hormone; D012333:RNA, Messenger