Frequent administration of abaloparatide shows greater gains in bone anabolic window and bone mineral density in mice: A comparison with teriparatide
| Autor: | Yoshimasa Takahashi, Tomoka Hasegawa, Hideko Takagi, Norio Amizuka, Akito Makino, Naoki Hase |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
medicine.medical_specialty Histology Physiology Endocrinology Diabetes and Metabolism Abaloparatide Osteoporosis 030209 endocrinology & metabolism Bone resorption Bone remodeling Mice 03 medical and health sciences 0302 clinical medicine Bone Density Teriparatide Anabolic window hemic and lymphatic diseases Internal medicine medicine Animals Humans Bone mineral Bone Density Conservation Agents business.industry Parathyroid Hormone-Related Protein medicine.disease Preclinical study 030104 developmental biology medicine.anatomical_structure Endocrinology Metabolic window Cortical bone business medicine.drug |
| Zdroj: | Bone. 142:115651 |
| ISSN: | 8756-3282 |
| DOI: | 10.1016/j.bone.2020.115651 |
| Popis: | 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 h), twice daily (BID, 15 μg/kg every 12 h), or three times a day (TID, 10 μg/kg every 8 h). 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 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, our findings would help elucidate the mechanism by which ABL shows excellent BMD gain and reduction of fractures in patients with osteoporosis. |
| Databáze: | OpenAIRE |
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