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Cited by 784

The DOI matches its Crossref record; 40 of the 40 references it cites were found in a registry or an index.

Sclerostin Antibody Treatment Increases Bone Formation, Bone Mass, and Bone Strength in a Rat Model of Postmenopausal Osteoporosis

Li, Xiaodong, Ominsky, Michael S, Warmington, Kelly S, Morony, Sean, Gong, Jianhua, Cao, Jin, Gao, Yongming, Shalhoub, Victoria, Tipton, Barbara, Haldankar, Raj, Chen, Qing, Winters, Aaron, Boone, Tom, Geng, Zhaopo, Niu, Qing-Tian, Ke, Hua Zhu, Kostenuik, Paul J, Simonet, W Scott, Lacey, David L, Paszty, Chris·2009·Journal of Bone and Mineral Research
DOI 10.1359/jbmr.081206
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Abstract

The development of bone-rebuilding anabolic agents for potential use in the treatment of bone loss conditions, such as osteoporosis, has been a long-standing goal. Genetic studies in humans and mice have shown that the secreted protein sclerostin is a key negative regulator of bone formation, although the magnitude and extent of sclerostin's role in the control of bone formation in the aging skeleton is still unclear. To study this unexplored area of sclerostin biology and to assess the pharmacologic effects of sclerostin inhibition, we used a cell culture model of bone formation to identify a sclerostin neutralizing monoclonal antibody (Scl-AbII) for testing in an aged ovariectomized rat model of postmenopausal osteoporosis. Six-month-old female rats were ovariectomized and left untreated for 1 yr to allow for significant estrogen deficiency-induced bone loss, at which point Scl-AbII was administered for 5 wk. Scl-AbII treatment in these animals had robust anabolic effects, with marked increases in bone formation on trabecular, periosteal, endocortical, and intracortical surfaces. This not only resulted in complete reversal, at several skeletal sites, of the 1 yr of estrogen deficiency-induced bone loss, but also further increased bone mass and bone strength to levels greater than those found in non-ovariectomized control rats. Taken together, these preclinical results establish sclerostin's role as a pivotal negative regulator of bone formation in the aging skeleton and, furthermore, suggest that antibody-mediated inhibition of sclerostin represents a promising new therapeutic approach for the anabolic treatment of bone-related disorders, such as postmenopausal osteoporosis.

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Metadata

Authors
Li, X., Ominsky, M. S., Warmington, K. S., Morony, S., Gong, J., Cao, J., Gao, Y., Shalhoub, V., Tipton, B., Haldankar, R., Chen, Q., Winters, A., Boone, T., Geng, Z., Niu, Q.-T., Ke, H. Z., Kostenuik, P. J., Simonet, W. S., Lacey, D. L., & Paszty, C.
Venue
Journal of Bone and Mineral Research
Publisher
Oxford University Press (OUP)
Published
2009-04-01
Volume
24
Issue
4
Pages
578-588
ISSN
  • 0884-0431 (ISSN-L)
  • 1523-4681
DOI
10.1359/jbmr.081206
OpenAlex
W1983220846
Cited by
784
References
40
FWCI
46.68
Type
journal article
Language
en
Open access
closed

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CoChat. (2026). Citation check: Sclerostin Antibody Treatment Increases Bone Formation, Bone Mass, and Bone Strength in a Rat Model of Postmenopausal Osteoporosis. https://app.cochat.ai/papers/10.1359/jbmr.081206
The paper
Li, X., Ominsky, M. S., Warmington, K. S., Morony, S., Gong, J., Cao, J., Gao, Y., Shalhoub, V., Tipton, B., Haldankar, R., Chen, Q., Winters, A., Boone, T., Geng, Z., Niu, Q.-T., Ke, H. Z., Kostenuik, P. J., Simonet, W. S., Lacey, D. L., & Paszty, C. (2009). Sclerostin Antibody Treatment Increases Bone Formation, Bone Mass, and Bone Strength in a Rat Model of Postmenopausal Osteoporosis. Journal of Bone and Mineral Research. https://doi.org/10.1359/jbmr.081206

Data sources

Bibliographic data: Semantic Scholar, OpenAlex, Crossref.

Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).

Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.