Frequent administration of abaloparatide shows greater gains in bone anabolic window and bone mineral density in mice: A comparison with teriparatide
Open accessAbstract
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.
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BLCs can react to PTH exposure by quickly reverting to osteoblasts and thus expand the osteoblastic pool to fill resorption lacunae.
“For example, BLCs can react to PTH exposure by quickly reverting to osteoblasts and thus expand the osteoblastic pool258 to fill resorption lacunae, similar to process in the “anabolic window” after teriparatide and abaloparatide administration.259”
From Bone remodeling: an operational process ensuring survival and bone mechanical competence (2022) · cites this paper as [259]
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Bone remodeling: an operational process ensuring survival and bone mechanical competence
Bolamperti, S., Villa, I., & Rubinacci, A. (2022) · Bone Research · doi:10.1038/s41413-022-00219-8 · Cited by 482 · see citing works
- Authors
- Makino, A., Hasegawa, T., Takagi, H., Takahashi, Y., Hase, N., & Amizuka, N.
- Affiliations
- Hokkaido University (JP)
- Teijin Pharma Limited (Japan) (JP)
- Corresponding author
- Makino, Akito
- Venue
- Bone
- Publisher
- Elsevier BV
- Published
- 2021-01
- Volume
- 142
- Pages
- 115651
- ISSN
- 1873-2763 (ISSN-L)
- 8756-3282
- OpenAlex
- W3087151445
- Cited by
- 22
- References
- 26
- Citations by year
- 2026: 3 · 2025: 2 · 2024: 4 · 2023: 2 · 2022: 5 · 2021: 6
- FWCI
- 3.24
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Bone (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Hokkaido University Collection of Scholarly and Academic Papers (Hokkaido University) (submittedVersion, cc-by)
- Institutional Repositories DataBase (IRDB) (submittedVersion, cc-by)
- Funders
- Radius Health
- Topics
- Health Sciences › Medicine › Orthopedics and Sports Medicine › Bone health and osteoporosis research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bone Metabolism and Diseases
- Health Sciences › Medicine › Oncology › Bone health and treatments
- Keywords
- abaloparatide, teriparatide, bone mineral density, administration frequency, bone formation, bone resorption, bone turnover markers, bone histomorphometry, EphB4, bone remodeling, osteoporosis
- MeSH terms
- Animals, Humans, Bone Density, Teriparatide, Parathyroid Hormone-Related Protein, Bone Density Conservation Agents, Mice
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