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Subcutaneous administration of lactone form of simvastatin stimulates ectopic osteoinduction by rhBMP‐2
Author(s) -
Sugiyama T,
Nakagawa T,
Sato C,
Fujii T,
Mine K,
Shimizu K,
Murata T,
Tagawa T
Publication year - 2007
Publication title -
oral diseases
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.953
H-Index - 87
eISSN - 1601-0825
pISSN - 1354-523X
DOI - 10.1111/j.1601-0825.2006.01271.x
Subject(s) - simvastatin , alkaline phosphatase , chemistry , acid phosphatase , endocrinology , cerivastatin , bone morphogenetic protein , medicine , bone formation , calcium , urology , enzyme , biochemistry , reductase , gene
Objective: To evaluate the effects of various 3‐hydroxy‐3‐methylglutaryl‐coenzyme A reductase inhibitors (statins) on ectopic osteoinduction by recombinant human bone morphogenetic protein‐2 (rhBMP‐2) using different administration methods. Materials and methods: Disks containing 5 μ g of rhBMP‐2 and type I collagen were implanted into the calf muscles of 6‐week‐old male rats ( n = 64). Either the lactone form of simvastatin (SV), open hydroxy‐acid form of simvastatin (SVA), cerivastatin (CVA), or vehicle (control) was then administered per orally (PO group) or subcutaneously (SC group) for 20 days. The disks were removed on day 21 after implantation, and ectopic induced bone formation was evaluated by radiographic, histologic, and biochemical analysis. Results: Both the projected and radiopaque area on X‐ray film, and the calcium content of the SV group in the SC group (SV–SC group) were significantly greater than those in the other SC and PO groups. Alkaline phosphatase activity and tartrate‐resistant acid phosphatase activity in the SV–SC group were significantly lower than those in the other SC and PO groups. Histologic examination revealed an increase of ectopic induced bone volume in the SV–SC group. Conclusion: Subcutaneous administration of SV stimulates ectopic osteoinduction by rhBMP‐2 through reduction of bone turnover.