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Review
. 2018 Jun;10(5-6):105-115.
doi: 10.1177/1759720X18775936. Epub 2018 Jun 7.

The clinical potential of romosozumab for the prevention of fractures in postmenopausal women with osteoporosis

Anne Sophie Koldkjær Sølling  1 , Torben Harsløf  1 , Bente Langdahl  2
Affiliations
Review

The clinical potential of romosozumab for the prevention of fractures in postmenopausal women with osteoporosis

Anne Sophie Koldkjær Sølling et al. Ther Adv Musculoskelet Dis. 2018 Jun.

Abstract

The glycoprotein sclerostin inhibits activation of the canonical Wnt pathway and thereby suppresses bone formation by inhibiting the osteoblasts. Additionally, sclerostin increases bone resorption by stimulating the production of receptor activator of nuclear factor kappa-β-ligand (RANKL). Romosozumab (ROMO) is a monoclonal antibody against sclerostin. Phase III clinical trials in postmenopausal women with osteoporosis have shown that ROMO increases bone mineral density at the lumbar spine and hip and reduces the risk of vertebral and clinical fractures in comparison with placebo. In women with severe osteoporosis, ROMO reduces the risk of vertebral, nonvertebral and clinical fractures in comparison with alendronate. ROMO is the first treatment for osteoporosis with dual action, and may become a valuable tool for improving the treatment of osteoporosis. At present, the approval of ROMO by the authorities is awaiting further investigations of a potential increased risk of cardiovascular events associated with ROMO treatment.

Keywords: fracture; osteoporosis; review; romosozumab; sclerostin.

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Conflict of interest statement

Conflict of interest statement: Torben Harsløf received lecture fees from Amgen, Astra Zeneca, and Eli Lilly. Bente Langdahl serves on advisory boards for Amgen, Eli Lilly, and UCB and has received lecture fees from Merck, Eli Lilly, TEVA and Amgen. Anne Sophie Koldkjær Sølling has nothing to disclose.

Figures

Figure 1.
Figure 1.
The Wnt signalling pathway. Left: the Wnt pathway is activated by the interaction between LRP5/6, Wnt and Frizzled. Beta-catenin is released and enters the nucleus and activates transcription from Wnt target genes. Right: the Wnt pathway is inactivated due to sclerotin binding to LRP5/6 and beta-catenin is phosphorylated and degraded. Illustration courtesy of Alessandro Baliani© 2018. LRP5/6, low-density lipoprotein receptor protein 5 and 6; β-cat, beta-catenin; Axin, a scaffold protein; APC, adenomatous polyposis coli (tumor suppressor protein); GSK3β, glycogen synthase kinase 3 beta; P, phosphate; CK1α, casein kinase 1 alpha; DSH, disheveled (cytoplasmic protein).
Figure 2.
Figure 2.
Romosozumab mode of action. Illustration courtesy of Alessandro Baliani© 2018. RANKL, receptor activator of nuclear factor kappa-β-ligand; Scl, sclerostin.
See this image and copyright information in PMC

References

    1. Baron R, Rawadi G. Minireview: targeting the Wnt/β-catenin pathway to regulate bone formation in the adult skeleton Endocrinology 2007; 148: 2635–2643. - PubMed
    1. Thompson ML, Jimenez-Andrade JM, Mantyh PW. Sclerostin immunoreactivity increases in cortical bone osteocytes and decreases in articular cartilage chondrocytes in aging mice. J Histochem Cytochem 2016; 64: 179–189. - PMC - PubMed
    1. Roudier M, Li X, Niu QT, et al. Sclerostin is expressed in articular cartilage but loss or inhibition does not affect cartilage remodeling during aging or following mechanical injury. Arthritis Rheum 2013; 65: 721–731. - PubMed
    1. Poole KE, Van Bezooijen RL, Loveridge N, et al. Sclerostin is a delayed secreted product of osteocytes that inhibits bone formation FASEB J 2005; 19: 1842–1844. - PubMed
    1. Van Bezooijen RL, Roelen BA, Visser A, et al. Sclerostin is an osteocyte-expressed negative regulator of bone formation, but not a classical BMP antagonist. J Exp Med 2004; 199: 805–814. - PMC - PubMed

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