Long-term effect of incadronate disodium (YM-175) on fracture healing of femoral shaft in growing rats

Citation
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
Citations number
37
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Endocrinology, Nutrition & Metabolism
Journal title
JOURNAL OF BONE AND MINERAL RESEARCH
ISSN journal
0884-0431 → ACNP
Volume
16
Issue
3
Year of publication
2001
Pages
429 - 436
Database
ISI
SICI code
0884-0431(200103)16:3<429:LEOID(>2.0.ZU;2-X
Abstract
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.