Tags

Type your tag names separated by a space and hit enter

Sclerostin antibody treatment increases bone formation, bone mass, and bone strength in a rat model of postmenopausal osteoporosis.
J Bone Miner Res. 2009 Apr; 24(4):578-88.JB

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.

Authors+Show Affiliations

Department of Metabolic Disorders, Amgen, Thousand Oaks, California 91320-1799, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

19049336

Citation

Li, Xiaodong, et al. "Sclerostin Antibody Treatment Increases Bone Formation, Bone Mass, and Bone Strength in a Rat Model of Postmenopausal Osteoporosis." Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research, vol. 24, no. 4, 2009, pp. 578-88.
Li X, Ominsky MS, Warmington KS, et al. Sclerostin antibody treatment increases bone formation, bone mass, and bone strength in a rat model of postmenopausal osteoporosis. J Bone Miner Res. 2009;24(4):578-88.
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 : the Official Journal of the American Society for Bone and Mineral Research, 24(4), 578-88. https://doi.org/10.1359/jbmr.081206
Li X, et al. Sclerostin Antibody Treatment Increases Bone Formation, Bone Mass, and Bone Strength in a Rat Model of Postmenopausal Osteoporosis. J Bone Miner Res. 2009;24(4):578-88. PubMed PMID: 19049336.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Sclerostin antibody treatment increases bone formation, bone mass, and bone strength in a rat model of postmenopausal osteoporosis. AU - Li,Xiaodong, AU - Ominsky,Michael S, AU - Warmington,Kelly S, AU - Morony,Sean, AU - Gong,Jianhua, AU - Cao,Jin, AU - Gao,Yongming, AU - Shalhoub,Victoria, AU - Tipton,Barbara, AU - Haldankar,Raj, AU - Chen,Qing, AU - Winters,Aaron, AU - Boone,Tom, AU - Geng,Zhaopo, AU - Niu,Qing-Tian, AU - Ke,Hua Zhu, AU - Kostenuik,Paul J, AU - Simonet,W Scott, AU - Lacey,David L, AU - Paszty,Chris, PY - 2008/12/4/pubmed PY - 2009/7/17/medline PY - 2008/12/4/entrez SP - 578 EP - 88 JF - Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research JO - J Bone Miner Res VL - 24 IS - 4 N2 - 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. SN - 1523-4681 UR - https://www.unboundmedicine.com/medline/citation/19049336/Sclerostin_antibody_treatment_increases_bone_formation_bone_mass_and_bone_strength_in_a_rat_model_of_postmenopausal_osteoporosis_ L2 - https://doi.org/10.1359/jbmr.081206 DB - PRIME DP - Unbound Medicine ER -