Concentration of bisphosphonate (incadronate) in callus area and its effects on fracture healing in rats.
The aim of the present study was to investigate effects of incadronate on early stages of fracture healing and to detect its concentration in callus area (Ca.Ar). Rats were injected three times per week with either two doses of incadronate (10 microg/kg and 100 microg/kg) or vehicle for 2 weeks. Femora were then fractured and fixed and animals were divided into pretreatment (P-10 and P-100) and continuous treatment (C-10 and C-100) groups. Incadronate treatment was stopped in P-10 and P-100 groups but continued in C-10 and C-100 groups. Animals were killed at 2 weeks and 4 weeks after fracture. Results showed significantly large callus, compared with the control, only in C-100 group at 4 weeks but not at 2 weeks. Both linear labeled surface (LS) and eroded surface (ES) decreased significantly in C-10 and C-100 groups at 2 weeks and 4 weeks. Osteoclast number (N.Oc) decreased significantly in C-10 and C-100 groups at 2 weeks but increased slightly at 4 weeks. However, there was no significant difference in the above parameters in P-10 and P-100 groups at 4 weeks. Apoptotic osteoclasts were observed only in the C-100 group at 4 weeks. A time-course decrease in incadronate concentration was detected in P-10 and P-100 groups whereas an increase was observed in C-10 and C-100 groups. These findings suggest that larger callus under incadronate treatment may result from the inhibition of bone resorption, histological characteristics of callus may be correlated with incadronate concentration, and metabolism of incadronate in bone may be related to the rate of bone turnover.
Li
J
J
Department of Orthopedic Surgery, Kagawa Medical University, Kita-gun, Japan.
Mori
S
S
Kaji
Y
Y
Kawanishi
J
J
Akiyama
T
T
Norimatsu
H
H
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D002146:Bony Callus / Q000166:cytology / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000378:metabolism*; D002452:Cell Count; D004164:Diphosphonates / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology* / Q000627:therapeutic use; D005260:Female; D005264:Femoral Fractures / Q000000981:diagnostic imaging / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D006651:Histocytochemistry; D017403:In Situ Hybridization; D010010:Osteoclasts / Q000166:cytology / Q000000981:diagnostic imaging / Q000187:drug effects; D011859:Radiography; D051381:Rats; D017207:Rats, Sprague-Dawley; D014945:Wound Healing / Q000187:drug effects*
D004164:Diphosphonates; C071542:cimadronate