Departmental Bulletin Paper 全身的副甲状腺ホルモン間歇投与が骨造成部での骨形成に及ぼす影響

伊藤, 理妙  ,  田辺, 俊一郎  ,  山田, 尚子  ,  長谷川, ユカ  ,  近藤, 雄三  ,  高橋, 潤  ,  永原, 國央

Description
副甲状腺ホルモン(PTH)の間歇投与により骨形成を促進することから、副作用が少なく、減少した骨量を増加させることで、現在、骨粗鬆症治療に応用され、病的骨折を予防すると報告されている。本研究では、歯科インプラント治療のために骨造成が必要な症例に対して、PTH間歇投与による骨形成活性状態の獲得を目的とした動物実験による基礎研究を行った。実験動物には、ビーグル犬3頭を用いた。両側下顎第4前臼歯と第1後臼歯を抜歯し、4週間後に同部位に骨欠損(5mm×5mm×15mm)を作成した。同骨欠損部に対し6週後に、チタンメッシュを応用したGBR処置を行った。PTHは、遺伝子組換えヒトPTH製剤(h-PTH)を用い、生理的食塩液(PS)投与したものと比較した。h-PTHは体重1kgあたり1回6μgとし、隔日で1週間に3回、頸部に皮下注射した。投与期間は、GBR処置前2週間(GBR前投与群)と、GBR処置後2週間(GBR後投与群)とした。GBR処置後3週間後に下顎骨を摘出し、マイクロCTによる観察を行い、下顎骨のBMD画像を作成し、骨欠損部の新生骨を含む全組織量(TV)、新生骨の骨量(BV)、新生骨の骨密度(BMD)、新生骨の骨塩量(BMC)、BV/TV(%)、骨表面積(BS)を計測した結果、BVはPS投与群5.89mm3、GBR前投与群8.9mm3、GBR後投与群5.25mm3であった。BV/TVは、PS投与群GBR25.6%、GBR前投群与41.0%、GBR後投与群43.1%であった。BMDは、PS投与群465.2mg/cm3、GBR前投与群520.3mg/cm3、GBR後投与群494.5mg/cm3、BMCは、PS投与群27.4mg、GBR前投与群46.3mg、GBR後投与群26mgであった。BSはPS投与群303.7mm2、GBR前投与群262.3mm2、GBR後投与群204mm2といずれもh-PTH投与により、GBR処置部位の骨形成が、PS投与群と比較して速やかに行われ、GBR処置後3週目に成熟した骨形成されたことから、PTH投与により骨形成活性を獲得できることが示唆された。Intermittent parathormone (PTH) injection will prevent a morbid bone fracture by increasing the bone mass to promote osteogenic activity was reported. In this study, we performed basic research for the purpose of investigating whether intermittent PTH injection could acquire an osteogenic activity state for the case of bone augmentaion needed for dental implant treatment. Three beagles dogs mandibular fourth premolar and first molar in both sides were extracted and bone defect (5mm ×5mm ×15mm) after four weeks teeth extraction was made. Then after six weeks, the GBR treatment for the bone defect was performed using titanium mesh and screw fixation. Recombinant human Parathyroid hormone (PTH),6μg/kg was prepared and subcutaneously injected in three times in a week 2 weeks before or 2 weeks after GBR treatment.We prepared two groups for this study. One is injected for two weeks before GBR treatment (before GBR) and the other is injected for two weeks after GBR treatment (after GBR). After three weeks GBR treatment,the mandible were removed and proceeded by the micro-CT analysis. The condition to analyze with micro-CT photography were; tube voltage 70.5kV, a tube electric current for this study. One is injected for two weeks before GBR treatment (before GBR) and the other is injected for two weeks after GBR treatment (after GBR). After three weeks GBR treatment,the mandible were removed and proceeded by the micro-CT analysis. The condition to analyze with micro-CT photography were; tube voltage 70.5kV, a tube electric current 114.5 μA, geometric amplifi cation 4.861 times, a condition of resolution 20.574μm/pixel. And the data were used to made mandibular BMD image with image analysis software (TRY/3D-BON BMD), and measured all organization quantity (TV), bone mass (BV), bone density (BMD), bone mineral density (BMC), BV/TV (%), bone surface area (BS) including the new formed bone at the bone defect area. Results; BV was 5.25mm3 for after GBR, 8.9mm3 for before GBR and 5.89mm3 for PS injection. BV/TV was 43.1% for after GBR, 41.0% for before GBR and 25.6% for PS injection. BMD was 494.5mg/cm3 for after GBR, 520.3mg/cm3 for before GBR and 465.2mg/cm3 for PS injection. BMC was 26.0mg after GBR, 46.3mg for before GBR and 27.4mg for PS injection. BS was 204 mm2 for after GBR, 262.3mm2 for before GBR and 303.7mm2 for PS injection. According to these findings, we concluded that osteogenic activity was able to acquire by intermittent PTH injection because the bone formation was enhauced at the GBR treatment area with the PTH injection compared to PS injection, and a mature bone was formed three weeks later of GBR treatment.
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