The effect of PTH(1-34) on fracture healing during different loading conditions

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  • Maria Ellegaard
  • ,
  • Tina Kringelbach
  • ,
  • Susanne Syberg
  • ,
  • Solveig Petersen
  • ,
  • Jens-Erik Beck Jensen, Institut for Klinisk Medicin, Danmark
  • Annemarie Brüel
  • Niklas Rye Jørgensen, Danmark
  • Peter Schwarz, Ortopædi og Intern Medicin, Danmark
Parathyroid hormone (PTH) and PTH(1-34) have been shown to promote bone healing in several animal studies. It is known that the mechanical environment is important in fracture healing. Furthermore, PTH and mechanical loading has been suggested to have synergistic effects on intact bone. The aim of the present study was to investigate whether the effect of PTH(1-34) on fracture healing in rats was influenced by reduced mechanical loading. For this purpose we used female, 25-week-old ovariectomized rats. Animals were subjected to closed midshaft fracture of the right tibia ten weeks after ovariectomy. Five days before fracture, half of the animals received Botulinum Toxin A-injections in the muscles of the fractured leg to induce muscle paralysis (unloaded group), while the other half received saline injections (control group). For the following eight weeks, half of the animals in each group received injections of hPTH(1-34) (20 µg/kg/day) and the other half received vehicle treatment. Fracture healing was assessed by radiology, DXA, histology and bone strength analysis. We found that unloading reduced callus area significantly, while no effects of PTH(1-34) on callus area were seen in neither normally nor unloaded animals. PTH(1-34) increased callus bone mineral density (BMD) and bone mineral content (BMC) significantly, while unloading decreased callus BMD and BMC significantly. PTH(1-34)-treatment increased bone volume of the callus in both unloaded and control animals. PTH(1-34)-treatment increased ultimate force of the fracture by 63% in both control and unloaded animals and no interaction of the two interventions could be detected. PTH(1-34) was able to stimulate bone formation in normally loaded as well as unloaded intact bone. In conclusion, the study confirms the stimulatory effect of PTH(1-34) on fracture healing and our data suggest that PTH(1-34) is able to promote fracture healing, as well as intact bone formation during conditions of reduced mechanical loading.
TidsskriftJournal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research
StatusUdgivet - 13 apr. 2013

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