Tissue-level mechanisms responsible for the increase in bone formation and bone volume by sclerostin antibody
Open accessAbstract
Bone formation can be remodeling-based (RBF) or modeling-based (MBF), the former coupled to bone resorption and the latter occurring directly on quiescent surfaces. Unlike osteoanabolic therapies such as parathyroid hormone (PTH) 1-34 that increase bone remodeling and thus both formation and resorption, sclerostin antibody (Scl-Ab) increases bone formation while decreasing bone resorption. With this unique profile, we tested our hypothesis that Scl-Ab primarily elicited MBF by examining bones from Scl-Ab–treated ovariectomized (OVX) rats and male cynomolgus monkeys (cynos). Histomorphometry was performed to quantify and characterize bone surfaces in OVX rats administered vehicle or Scl-Ab (25 mg/kg) subcutaneously (sc) twice/week for 5 weeks and in adolescent cynos administered vehicle or Scl-Ab (30 mg/kg) sc every 2 weeks for 10 weeks. Fluorochrome-labeled surfaces in L2 vertebra and femur endocortex (cynos only) were considered to be MBF or RBF based on characteristics of their associated cement lines. In OVX rats, Scl-Ab increased MBF by eightfold (from 7% to 63% of bone surface, compared to vehicle). In cynos, Scl-Ab markedly increased MBF on trabecular (from 0.6% to 34%) and endocortical surfaces (from 7% to 77%) relative to vehicle. Scl-Ab did not significantly affect RBF in rats or cynos despite decreased resorption surface in both species. In cynos, Scl-Ab resulted in a greater proportion of RBF and MBF containing sequential labels from week 2, indicating an increase in the lifespan of the formative site. This extended formation period was associated with robust increases in the percent of new bone volume formed. These results demonstrate that Scl-Ab increased bone volume by increasing MBF and prolonged the formation period at both modeling and remodeling sites while reducing bone resorption. Through these unique effects on bone formation and resorption, Scl-Ab may prove to be an effective therapeutic to rapidly increase bone mass in diseases such as osteoporosis. © 2014 American Society for Bone and Mineral Research.
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Romosozumab is a potent treatment option, both alone and in combination with other drugs.
“Romosozumab is a potent treatment option, both alone and in combination with other drugs [86].”
From Osteoporosis: Molecular Pathology, Diagnostics, and Therapeutics (2023) · cites this paper as [86]
The Introduction (page not provided) describes sclerostin antibody as a potential osteoporosis treatment, and the Study design identifies the antibody given to monkeys as romosozumab. The paper reports effects of romosozumab given alone in animals, but does not establish it as a potent clinical treatment. The combination discussed in the Discussion (page not provided) is denosumab with PTH 1-34, not romosozumab with another drug. (LLM, conf=0.88)
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- Authors
- Ominsky, M. S., Niu, Q.-T., Li, C., Li, X., & Ke, H. Z.
- Affiliations
- Amgen (United States) (US)
- Corresponding author
- Ominsky, Michael S
- Venue
- Journal of Bone and Mineral Research
- Publisher
- Oxford University Press (OUP)
- Published
- 2013-11-25
- Volume
- 29
- Issue
- 6
- Pages
- 1424-1430
- ISSN
- 0884-0431 (ISSN-L)
- 1523-4681
- OpenAlex
- W1582533387
- Cited by
- 167
- References
- 20
- Citations by year
- 2026: 5 · 2025: 9 · 2024: 9 · 2023: 12 · 2022: 12 · 2021: 17 · 2020: 27 · 2019: 9 · 2018: 11 · 2017: 11 · 2016: 24 · 2015: 15 · 2014: 6
- FWCI
- 15.35
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model (vor)
- Locations
- Journal of Bone and Mineral Research (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Amgen
- UCB Pharma
- 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
- sclerostin antibody, bone formation, bone remodeling, bone modeling, bone resorption, anabolic therapy, ovariectomy, bone volume, trabecular bone, fluorescent labeling, bone histomorphometry, osteoporosis, Macaca fascicularis, rats
- MeSH terms
- Animals, Antibodies, Bone and Bones, Female, Genetic Markers, Macaca fascicularis, Male, Organ Specificity, Organ Size, Osteogenesis, Ovariectomy, Bone Remodeling, Rats, Sprague-Dawley, Bone Morphogenetic Proteins
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