Effects of Simvastatin on bone healing around titanium implants in osteoporotic rats.
OBJECTIVE
Osteoporosis is known to impair the process of implant osseointegration. The recent discovery that statins (HMG-CoA reductase inhibitors) act as bone anabolic agents suggests that statins can be used as potential agents in the treatment of osteoporosis. Therefore, we hypothesized that statins will promote osteogenesis around titanium implants in subjects with osteoporosis.


METHODS
Fifty-four female Sprague Dawley rats, aged 3 months old, were randomly divided into three groups: Sham-operated group (SHAM; n=18), ovariectomized group (OVX; n=18), and ovariectomized with Simvastatin treatment group (OVX+SIM; n=18). Fifty-six days after being ovariectomized (OVX), screw-shaped titanium implants were inserted into the tibiae. Simvastatin was administered orally at 5 mg/kg each day after the placement of the implant in the OVX+SIM group. The animals were sacrificed at either 28 or 84 days after implantation and the undecalcified tissue sections were obtained. Bone-to-implant contact (BIC) and bone area (BA) within the limits of implant threads were measured around the cortical (zone A) and cancellous (zone B) bone regions. Furthermore, bone density (BD) of zone B in a 500 microm wide zone lateral to the implants was also measured.


RESULTS
There were no significant differences in BIC and BA measurements in zone A in any of the three groups at either 28 or 84 days after implantation (P>0.05). By contrast, in zone B, significant differences in the measurement of BIC, BA, and BD were observed at 28 and 84 days between all three groups. Bone healing decreased with lower BIC, BA, and BD around implant in OVX group compared with other two groups, and Simvastatin reversed the negative effect of OVX on bone healing around implants with the improvement of BIC, BA, and BD in zone B.


CONCLUSIONS
Osteoporosis can significantly influence bone healing in the cancellous bone around titanium implants and Simvastatin was shown to significantly improve the osseointegration of pure titanium implants in osteoporotic rats.
Du
Zhibin
Z
Department of Oral Implant, Affiliated Stomatological Hospital of Fujian Medical University, Fuzhou, China.
Chen
Jiang
J
Yan
Fuhua
F
Xiao
Yin
Y
D000818:Animals; D015519:Bone Density / Q000187:drug effects; D050071:Bone Density Conservation Agents / Q000627:therapeutic use*; D001863:Bone Screws; D015921:Dental Implants; D003764:Dental Materials; D005260:Female; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D016348:Osseointegration / Q000187:drug effects; D010012:Osteogenesis / Q000187:drug effects; D010024:Osteoporosis / Q000188:drug therapy* / Q000473:pathology; D010052:Ovariectomy; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D019821:Simvastatin / Q000627:therapeutic use*; D013977:Tibia / Q000187:drug effects* / Q000473:pathology; D013997:Time Factors; D014025:Titanium
D050071:Bone Density Conservation Agents; D015921:Dental Implants; D003764:Dental Materials; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D019821:Simvastatin; D014025:Titanium