ウサギの抜歯モデルにおける薬害顎骨壊死に対する軟部組織閉鎖の効果。パイロットスタディ

Effects of Soft Tissue Closure on Medication-Related Osteonecrosis of the Jaw in a Rabbit Model with Tooth Extraction: A Pilot Study.

抄録

目的:

本研究では、抜歯後の軟部組織閉鎖が、ウサギモデルにおける投薬関連顎骨壊死の予防に及ぼす効果を検討した。

Objectives: The study investigated the effect of soft tissue closure after tooth extraction on the prevention of medication-related osteonecrosis of the jaw in a rabbit model.

材料と方法:

雌のニュージーランドホワイトラビット20匹を、ゾレドロン酸（ZA）を投与する実験群と生理食塩水を投与する対照群に無作為に割り付けた。ZA/生理食塩水投与の4週間後に両側下顎小臼歯の抜歯を行った。抜歯後すぐに右下顎の傷口を縫合して閉じたが，反対側は開放したままとした。抜歯から4週間後および8週間後に動物を犠牲にした。骨の成長速度を評価するために，フルオロクローム標識液を皮下に注射した。下顎を採取し，マイクロコンピュータ断層撮影，共焦点顕微鏡，組織形態学的検査を行った。

Materials and Methods: Twenty female New Zealand white rabbits were randomly assigned into the experimental group administrated with zoledronic acid (ZA) and control groups treated with saline. Bilateral lower premolar extraction was performed 4 weeks after ZA/saline administration. Immediately after extraction, the wound on the right mandible was closed by suture while the other side was left open. Animals were sacrificed 4 weeks and 8 weeks after tooth extraction. Fluorochrome labeling solutions were injected subcutaneously to evaluate the bone growth rates. The mandibles were harvested and subjected for microcomputed tomography, confocal microscope, and histomorphological examinations.

結果:

すべての抜歯部位は、感染の兆候もなく良好に治癒した。海綿体厚さ（Tb.Th）は，4週目と8週目のいずれにおいても，ZA投与群が対照群よりも有意に高かったが，その他の評価項目には有意な差は認められなかった。下顎骨の骨成長率は，ZA投与群で徐々に低下した。組織学的解析の結果，8週目には，ZA投与群は対照群に比べて骨壊死の発生率が有意に高かったが，縫合側と非縫合側の間には有意差は認められなかった。

Results: All extraction sites healed well without any signs of infection. Trabecular thickness (Tb.Th) was significantly higher in the ZA-treated group than in the control group at both week 4 and week 8, while no significant difference was detected in the rest of the assessed parameters. The bone growth rate in mandibles showed gradual reduction in the ZA-treated group. Histological analysis showed that at week 8, the animals in the ZA-treated group had significantly higher incidence of osteonecrosis than that in the control group, while no significance was revealed between the sutured and nonsutured side.

結論:

ZA治療は、骨成長率を有意に低下させるが、骨密度と骨マイクロアーキテクチャーには有意な影響を及ぼさないことがわかった。ZA処理したウサギモデルでは、抜歯窩の軟部組織の閉鎖はONJの発生率を低下させない。

Conclusions: ZA treatment significantly reduces bone growth rates but does not reveal a significant effect on bone mineral density and bone microarchitecture. Soft tissue closure of the extraction socket does not reduce the incidence of ONJ in the ZA-treated rabbit model.