open access

https://doi.org/10.14943/doctoral.k13868

https://hdl.handle.net/2115/79663

アバロパラチドは骨形成促進作用により骨アナボリックウインドウを拡大させ、マウスの海綿骨及び皮質骨を増加させる : テリパラチドとの比較

英語

2020-03-25

Hokkaido University

40p

Abaloparatide (ABL) is a novel 34-amino acid peptide analog of parathyroid hormone-related protein. In clinical studies, although ABL showed a greater bone mineral density (BMD) increase than teriparatide (TPTD, human parathyroid hormone 1-34), the responses of ABL to bone formation and resorption markers were weaker, making it difficult to understand the relationship between the bone anabolic window (increase in bone formation versus resorption) and bone mass. In the present study, the effects of ABL and TPTD were compared in mice. Given that the rate of bone turnover is higher in rodents than in humans, the comparison was made with several administration regimens providing equivalent daily dosages: once daily (QD, 30 μg/kg every 24 hours), twice daily (BID, 15 μg/kg every 12 hours), or three times a day (TID, 10 μg/kg every 8 hours). Frequent administration of ABL showed higher BMD with enhancement of trabecular and cortical bone mass and structures than that of TPTD, consistent with the clinical results seen with once daily administration. ABL increased bone formation marker levels more than TPTD with more frequent regimens, while bone resorption marker levels were not different between ABL and TPTD in all regimens. Analysis of bone histomorphometry and gene expression also suggested that ABL increased bone formation more than TPTD, while the effect on bone resorption 3 was almost comparable between ABL and TPTD. The bone anabolic windows calculated from bone turnover markers indicated that ABL enhanced the anabolic windows more than TPTD, leading to a robust increase in BMD. The mechanism by which ABL showed a better balance of bone turnover was suggested to be partly due to the enhanced remodeling-based bone formation involved in Ephb4. Taken together, the author’s findings would help elucidate the mechanism by which ABL shows excellent BMD gain and reduction of fractures in patients with osteoporosis.

2020-03-25

甲第13868号

博士(歯学)

(主査) 教授 網塚 憲生, 教授 飯村 忠浩, 教授 田村 正人

歯学研究科（口腔医学専攻）

博士論文

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