Osteoconductive action of alendronate after implantation of beta tricalcium phosphate in rat adjuvant-induced arthritis.
The aim of the study was to determine the effect of alendronate on resorption of β-tricalcium phosphate (β-TCP) and bone formation in rats with adjuvant-induced arthritis (AIA). After preparation of a model of AIA in rats (day 0), alendronate or vehicle was injected intraperitoneally once daily five times in a week. Cylindrical β-TCP was implanted into the rat femoral condyle on day 7. Rats were killed on days 12, 15, and 21, and specimens and serum samples were collected. Specimens were analyzed by tartrate-resistant acid phosphate (TRAP) staining, immunohistochemistry of the ED1 protein, and in situ hybridization with digoxigenin-labeled α1 chain of type I procollagen (COL1A1). Mineralized bone sections were analyzed by Villanueva bone stain. The serum osteocalcin level was measured using an enzyme-linked immunosorbent assay kit. Alendronate decreased the number of TRAP-positive cells attached to β-TCP, the numbers of ED1-positive multinucleated giant cells, and resorption of β-TCP. In AIA rats treated with alendronate, COL1A1 mRNA-positive cells adhered to β-TCP were round or cuboid whereas the cells in untreated AIA rats were fibroblast-like cells. Alendronate increased calcification of newly formed bone whereas it did not restore the bone formation suppressed with inflammation. These results suggest that alendronate has the potential to conduct mature bone after implantation of β-TCP in AIA. Alendronate may help to reduce insufficiency of newly formed bone after implantation of β-TCP in diseases characterized by increased bone resorption such as rheumatoid arthritis.
Division of Orthopaedic Surgery, Department of Regenerative and Transplant Medicine, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.
Takahiro
T
Netsu
Naoki
N
Kondo
Katsumitsu
K
Arai
Akira
A
Ogose
Naoto
N
Endo
D000135:Acid Phosphatase / Q000378:metabolism; D019386:Alendronate / Q000494:pharmacology*; D000818:Animals; D001169:Arthritis, Experimental / Q000188:drug therapy; D002113:Calcification, Physiologic; D002130:Calcium Phosphates / Q000378:metabolism*; D024042:Collagen Type I / Q000096:biosynthesis; D000090602:Collagen Type I, alpha 1 Chain; D007527:Isoenzymes / Q000378:metabolism; D008297:Male; D015675:Osteocalcin / Q000097:blood; D010012:Osteogenesis / Q000187:drug effects*; D051381:Rats; D000071681:Tartrate-Resistant Acid Phosphatase
D002130:Calcium Phosphates; D024042:Collagen Type I; D000090602:Collagen Type I, alpha 1 Chain; D007527:Isoenzymes; C485817:beta-tricalcium phosphate; D015675:Osteocalcin; D000135:Acid Phosphatase; D000071681:Tartrate-Resistant Acid Phosphatase; D019386:Alendronate