1Alpha,25-dihydroxy-2beta(3-hydroxypropoxy)vitamin D3 (ED-71) suppressed callus remodeling but did not interfere with fracture healing in rat femora.
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.
Cao
Yongping
Y
Department of Orthopedic Surgery, Faculty of Medicine, Kagawa University, 1750-1 Ikenobe, Kita-gun Kagawa 761-0793, Japan.
Mori
Satoshi
S
Mashiba
Tasuku
T
Kaji
Yoshio
Y
Manabe
Takeshi
T
Iwata
Ken
K
Miyamoto
Kensaku
K
Komatsubara
Satoshi
S
Yamamoto
Tetsuji
T
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
D007527:Isoenzymes; D014807:Vitamin D; D000135:Acid Phosphatase; D000071681:Tartrate-Resistant Acid Phosphatase; D002117:Calcitriol; C547512:eldecalcitol