Long-Term Effect of Incadronate Disodium (YM-175) on Fracture Healing of Femoral Shaft in Growing Rats

Abstract

The aim of this study was to investigate the long-term effect of incadronate on fracture healing of the femoral shaft in rats. Female Sprague-Dawley 8-week-old rats were injected subcutaneously (sc) with either vehicle (V group) or two doses of incadronate (10 g/kg and 100 g/kg) three times a week for 2 weeks. Right femoral diaphysis was then fractured and fixed with intramedullary stainless wire. Just after fracture, incadronate treatment was 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 killed at 25 weeks or 49 weeks after surgery. Fractured femur was evaluated radiologically and mechanically and then stained in Villanueva bone stain and embedded in methyl methacrylate. Undecalcified cross-sections from the fracture area were evaluated microradiologically and histomorphometrically. Radiographic observation showed that the fracture line disappeared in all groups. Cross-sectional area in the C-100 group was the biggest among all groups and in the C-10 group was larger than that in the V group at 25 weeks. Histological and histomorphometric observations showed that the process of fracture healing was delayed under continuous treatment with incadronate as evidenced by the delay of both lamellar cortical shell formation and resolution of original cortex in C groups. Percent linear labeling perimeter, mineral apposition rate (MAR), and bone formation rate (BFR) in C groups significantly decreased compared with the other groups, indicating that the callus 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-term continuous treatment with incadronate delayed the process of fracture healing of femur in rats, especially under high dose but it did not impair the recovery of mechanical integrity of the fracture. (J Bone Miner Res 2001;16:429-436)

Long-term clinical study and multiscale analysis of in vivo biodegradation mechanism of Mg alloy

“…Histological slide preparations were carried out at the Ito Bone Histomorphometry Institute (Niigagta, Japan). Samples gathered from the animal models were placed in Villanueva bone stain solution for 4 d and dehydrated in sequence using EtOH according to the laboratory protocol (35). Dehydrated samples were embedded in methyl methacrylate resin for 20 d at 30∼40°C to create bone blocks.…”

Promotion by Collagen Tripeptide of Type I Collagen Gene Expression in Human Osteoblastic Cells and Fracture Healing of Rat Femur

“…The left (fractured) and right (control) femurs were then extirpated, and the progression of fracture healing was observed by soft X-ray exposure. The bone strength (stiffness and breaking load) was measured by the three-point bending test 7) with MZ-500D apparatus (Maruto, Tokyo, Japan). An isolated bone was horizontally fixed at both ends in the machine, and a probe was moved down (20 mm/min) at the mid-point of the bone.…”

Evidence for Using Bisphosphonate to Treat Legg-Calvé-Perthes Disease

“…While some data on the systemic skeletal effects of BP therapy in children with osteogenesis imperfecta have been reported in the literature [10,37,48], information on children with normal skeletons is scant. Decreased long-bone growth was observed in several animal studies [7,17,25,26] and postulated to be a dose-dependent effect where high-dose BPs were given to fast-growing animals. Such growth inhibition has not been seen in several clinical reports.…”