title: 1Alpha,25-dihydroxy-2beta(3-hydroxypropoxy)vitamin D3 (ED-71) suppressed callus remodeling but did not interfere with fracture healing in rat femora.
abstract: BACKGROUND
  Because osteoporotic patients are prone to fractures, it must be considered whether or not patients undergoing drug therapies should discontinue treatment after sustaining a non-vertebral fracture. This study has tested the effect of novel active vitamin D3 analog, 1alpha,25-dihydroxy-2beta(3-hydroxypropoxy)vitamin D3 (ED-71), on the fracture healing comparing with a powerful anti-resorptive agent, alendronate, using a rat femoral fracture model.
  
  
  METHODS
  Female SD rats (n=201) allocated into 6 groups were treated with MCT-vehicle and ED-71 at 0.025 and 0.05 microg/kg/day (EDL and EDH groups), and with saline-vehicle and alendronate at 5 and 10 microg/kg/day (ALL and ALH groups). After 4 weeks of pretreatment, osteotomy of the femur was performed. Treatment was continued until sacrifice at 6 and 16 weeks post-fracture. Fracture callus was evaluated by soft X-ray radiography, pQCT, biomechanical testing and histomorphometry.
  
  
  RESULTS
  At 16 weeks post-fracture, new cortical shell appeared in 100% of Control (MCT and saline-vehicle), EDL and EHL, and in 67% and 56% of ALL and ALH, respectively. ED-71 treatment showed insignificantly large callus area only at 6 weeks, while alendronate treatment induced bigger callus at both 6 and 16 weeks post-fracture. The lamellar/callus area was decreased only at 6 weeks by ED-71 treatment, but both at 6 and 16 weeks by alendronate treatment. Osteoclast number in callus surface was decreased in both ED-71 and alendronate treatment groups at 6 weeks and in EDH, ALL and ALH at 16 weeks, indicating that ED-71 inhibits osteoclastic bone resorption, but its effect is less prominent than alendronate. Almost complete callus remodeling was observed in ED-71-treated groups at 16 weeks without any significant change in structural and material properties of fractured bone.
  
  
  CONCLUSIONS
  ED-71 suppression of callus remodeling by inhibiting osteoclastic bone resorption was mild and dose-dependent and did not interfere with natural fracture healing process at 16 weeks post-fracture.
authors.affiliation: Department of Orthopedic Surgery, Faculty of Medicine, Kagawa University, 1750-1 Ikenobe, Kita-gun Kagawa 761-0793, Japan.
authors.forename: Yongping
authors.initials: Y
authors.lastname: Cao
authors.forename: Satoshi
authors.initials: S
authors.lastname: Mori
authors.forename: Tasuku
authors.initials: T
authors.lastname: Mashiba
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Kaji
authors.forename: Takeshi
authors.initials: T
authors.lastname: Manabe
authors.forename: Ken
authors.initials: K
authors.lastname: Iwata
authors.forename: Kensaku
authors.initials: K
authors.lastname: Miyamoto
authors.forename: Satoshi
authors.initials: S
authors.lastname: Komatsubara
authors.forename: Tetsuji
authors.initials: T
authors.lastname: Yamamoto
mesh_terms: D000135:Acid Phosphatase / Q000032:analysis; D000818:Animals; D016723:Bone Remodeling / Q000187:drug effects*; D002146:Bony Callus / Q000166:cytology / Q000000981:diagnostic imaging / Q000187:drug effects*; D002117:Calcitriol / Q000008:administration & dosage / Q000031:analogs & derivatives*; D004195:Disease Models, Animal; D005260:Female; D005264:Femoral Fractures / Q000000981:diagnostic imaging; D005269:Femur / Q000000981:diagnostic imaging / Q000187:drug effects / Q000502:physiology*; D017102:Fracture Healing / Q000187:drug effects*; D007527:Isoenzymes / Q000032:analysis; D011859:Radiography; D051381:Rats; D017207:Rats, Sprague-Dawley; D000071681:Tartrate-Resistant Acid Phosphatase; D014807:Vitamin D / Q000031:analogs & derivatives
chemical_list: D007527:Isoenzymes; D014807:Vitamin D; D000135:Acid Phosphatase; D000071681:Tartrate-Resistant Acid Phosphatase; D002117:Calcitriol; C547512:eldecalcitol