Cy. Li et al., Long-term effect of incadronate disodium (YM-175) on fracture healing of femoral shaft in growing rats, J BONE MIN, 16(3), 2001, pp. 429-436
The aim of this study was to investigate the long-term effect of incadronat
e on fracture healing of the femoral shaft in rats. Female Sprague-Dawley 8
-week-old rats were injected subcutaneously (sc) with either vehicle (V gro
up) or two doses of incadronate (10 mug/kg and 100 mug/kg) three times a me
ek for 2 weeks, Right femoral diaphysis was then fractured and fixed with i
ntramedullary stainless wire. Just after fracture, incadronate treatment wa
s stopped in pretreatment groups (P groups: P-10 and P-100) or continued in
continuous treatment groups (C groups: C-10 and C-100), All rats were kill
ed at 25 weeks or 49 weeks after surgery. Fractured femur was evaluated rad
iologically and mechanically and then stained in Villanueva bone stain and
embedded in methyl methacrylate, Undecalcified cross-sections from the frac
ture area were evaluated microradiologically and histomorphometrically. Rad
iographic observation showed that the fracture line disappeared in all grou
ps, Cross-sectional area in the C-100 group was the biggest among all group
s and in the C-10 group was larger than that in the V group at 25 weeks. Hi
stological and histomorphometric observations showed that the process of fr
acture healing was delayed under continuous treatment with incadronate as e
videnced by the delay of both lamellar cortical shell formation and resolut
ion of original cortex in C groups, Percent linear labeling perimeter, mine
ral apposition rate ((MAR), and bone formation rate (BFR) in C groups signi
ficantly decreased compared with the other groups, indicating that the call
us remodeling was suppressed under continuous treatment, especially with a
high dose. Mechanical study showed that the stiffness and ultimate load of
the fractured femur in the C 100 group were the highest among all groups at
both 25 weeks and 49 weeks, In conclusion, this study showed that long-ter
m continuous treatment with incadronate delayed the process of fracture hea
ling of femur in rats, especially under high dose but it did not impair the
recovery of mechanical integrity of the fracture.