Vertical bone augmentation with fluvastatin in an injectable delivery system: a rat study.
OBJECTIVE
HMG-CoA reductase inhibitors (statins) are widely used for hyperlipidemia. Previous studies demonstrate that statins stimulate bone morphogenetic protein-2 (BMP-2) expression and lead to bone formation. The aim of this study was to evaluate whether percutaneously injected statin with a novel statin delivery system achieved vertical bone augmentation.


METHODS
As experimental groups, atelocollagen-alpha-tricalcium phosphate (alphaTCP) composites containing 3.3 mg (low dose) or 6.7 mg (high dose) of fluvastatin were injected (one shot) subcutaneously over the calvarial periosteum of rats. The animals were then sacrificed 1, 2, and 4 weeks after injection. Vertically augmented bone was assessed by histomorphometric procedures, i.e., by measuring new bone thickness (NBT) and bone density (BD).


RESULTS
In control groups, no newly formed bone could be seen over the calvarial bone. In the experimental groups, in contrast, a large amount of newly formed bone could be seen over the preexisting calvarial bone. The newly formed bone was seen to be in direct contact with the preexisting bone. During the entire observation, significant NBT was observed in the experimental groups (P<0.05). At the final stage of observation (4 weeks), NBT was 66.7% (low-dose group) and 59.7% (high-dose group), while they were from 1% to 16.3% in the control groups. In the experimental groups, BD significantly increased in a time-dependent manner.


CONCLUSIONS
Percutaneously applied fluvastatin (one shot) with a composite of alphaTCP and collagen has great potential to augment the height of the bone.
Jinno
Yohei
Y
Section of Oral Rehabilitation, Faculty of Dental Science, Kyushu University, Higashi-ku, Fukuoka, Japan. jinno315@dent.Kyushu-u.ac.jp
Ayukawa
Yasunori
Y
Ogino
Yoichiro
Y
Atsuta
Ikiru
I
Tsukiyama
Yoshihiro
Y
Koyano
Kiyoshi
K
D000818:Animals; D001672:Biocompatible Materials / Q000008:administration & dosage / Q000494:pharmacology; D015519:Bone Density / Q000187:drug effects*; D002130:Calcium Phosphates / Q000008:administration & dosage / Q000494:pharmacology; D003094:Collagen / Q000008:administration & dosage / Q000494:pharmacology; D004337:Drug Carriers / Q000008:administration & dosage / Q000494:pharmacology; D016503:Drug Delivery Systems; D005229:Fatty Acids, Monounsaturated / Q000008:administration & dosage* / Q000494:pharmacology*; D005260:Female; D000077340:Fluvastatin; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage* / Q000494:pharmacology*; D007211:Indoles / Q000008:administration & dosage* / Q000494:pharmacology*; D010012:Osteogenesis / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D012886:Skull / Q000601:surgery*
D001672:Biocompatible Materials; D002130:Calcium Phosphates; D004337:Drug Carriers; D005229:Fatty Acids, Monounsaturated; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D007211:Indoles; C059821:atelocollagen; D000077340:Fluvastatin; D003094:Collagen; C018392:tricalcium phosphate