The effect of simvastatin on bone formation and ceramic resorption in a peri-implant defect model.
Experimental use of statins as stimulators of bone formation suggests they may have widespread applicability in the field of orthopaedics. With their combined effects on osteoblasts and osteoclasts, statins have the potential to enhance resorption of synthetic materials and improve bone ingrowth. In this study, the effect of oral and local administration of simvastatin to a beta tricalcium phosphate (betaTCP)-filled defect around an implant was compared with recombinant human bone morphogenetic protein 2 (rhBMP2). On hundred and sixty-two Sprague-Dawley rats were assigned to treatment groups: local application of 0.1, 0.9 or 1.7 mg of simvastatin, oral simvastatin at 5, 10 or 50 mg kg(-1) day(-1) for 20 days, local delivery of 1 or 10 microg of rhBMP2, or control. At 6 weeks rhBMP2 increased serum tartrate-resistant acid phosphatase 5b levels and reduced betaTCP area fraction, particle size and number compared with control, suggesting increased osteoclast activity. There was reduced stiffness and increased mechanical strength with this treatment. Local simvastatin resulted in a decreased mineral apposition rate at 6 weeks and increased fibrous area fraction, betaTCP area fraction, particle size and number at 26 weeks. Oral simvastatin had no effect compared with control. Local application of rhBMP2 increased resorption and improved mechanical strength whereas simvastatin was detrimental to healing. Oral simvastatin was ineffective at promoting either ceramic resorption or bone formation. The effect of statins on the repair of bone defects with graft substitute materials is influenced by its bioavailability. Thus, further studies on the optimal delivery system are needed.
Ma
Bingkui
B
Orthopaedic Research Unit, University of Cambridge, Box 180, Addenbrooke's Hospital, Hills Road, Cambridge CB2 2QQ, UK.
Clarke
Susan A
SA
Brooks
Roger A
RA
Rushton
Neil
N
D000818:Animals; D018786:Bone Substitutes / Q000378:metabolism*; D002130:Calcium Phosphates / Q000378:metabolism; D002516:Ceramics / Q000378:metabolism*; D020007:Implants, Experimental; D008297:Male; D010012:Osteogenesis / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D019821:Simvastatin / Q000008:administration & dosage / Q000494:pharmacology*; D013997:Time Factors
D018786:Bone Substitutes; D002130:Calcium Phosphates; C485817:beta-tricalcium phosphate; D019821:Simvastatin