Romosozumab for the treatment of osteoporosis

被引:119
作者
Bandeira, Leonardo [1 ]
Lewiecki, E. Michael [2 ]
Bilezikian, John P. [1 ]
机构
[1] Columbia Univ, Coll Phys & Surg, Med Ctr, Dept Med, New York, NY USA
[2] New Mexico Clin Res & Osteoporosis Ctr, 300 Oak St NE, Albuquerque, NM 87106 USA
关键词
Anabolic; bone mineral density; fracture; monoclonal antibody; osteoporosis; romosozumab; sclerostin; BONE-MINERAL DENSITY; RANDOMIZED CONTROLLED-TRIAL; PARATHYROID-HORMONE; 1-34; VAN-BUCHEM-DISEASE; POSTMENOPAUSAL WOMEN; SCLEROSTIN ANTIBODY; HIP FRACTURE; SOST GENE; RAT MODEL; IN-VITRO;
D O I
10.1080/14712598.2017.1280455
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 [微生物学]; 090105 [作物生产系统与生态工程];
摘要
Introduction: Sclerostin, a glycoprotein produced primarily by osteocytes, blocks the canonical Wnt signaling bone formation pathway. Romosozumab is a humanized monoclonal antibody to sclerostin that binds to sclerostin, permitting the engagement of Wnt ligands with their co-receptors, resulting in an increase in bone formation and bone mineral density (BMD). Clinical studies with romosozumab have shown dramatic improvements in BMD at the spine and hip. Romosozumab is associated with improvement in bone strength through mechanisms that include increases in bone formation and, different from classical osteoanabolic agents, suppression of bone resorption.Areas covered: Herein, the authors highlight the available data on romosozumab for the treatment of osteoporosis. This includes the latest data on the efficacy, pharmacokinetics and pharmacodynamics as well as safety and tolerability data.Expert opinion: Monthly subcutaneous dosing of romosozumab reduces the risk of vertebral and clinical fractures in women with postmenopausal osteoporosis, with a favorable balance of benefits and risks. Romosozumab is a promising emerging anabolic agent with a novel mechanism of action that may expand the options for treating osteoporotic patients at high risk of fracture.
引用
收藏
页码:255 / 263
页数:9
相关论文
共 72 条
[1]
Sclerostin Antibody Treatment Enhances Metaphyseal Bone Healing in Rats [J].
Agholme, Fredrik ;
Li, Xiaodong ;
Isaksson, Hanna ;
Ke, Hua Zhu ;
Aspenberg, Per .
JOURNAL OF BONE AND MINERAL RESEARCH, 2010, 25 (11) :2412-2418
[2]
WNT signalling pathways as therapeutic targets in cancer [J].
Anastas, Jamie N. ;
Moon, Randall T. .
NATURE REVIEWS CANCER, 2013, 13 (01) :11-26
[3]
The US Postmarketing Surveillance Study of Adult Osteosarcoma and Teriparatide: Study Design and Findings From the First 7 Years [J].
Andrews, Elizabeth B. ;
Gilsenan, Alicia W. ;
Midkiff, Kirk ;
Sherrill, Beth ;
Wu, Yun ;
Mann, Beth H. ;
Masica, Daniel .
JOURNAL OF BONE AND MINERAL RESEARCH, 2012, 27 (12) :2429-2437
[4]
A novel strategy for generating monoclonal antibodies from single, isolated lymphocytes producing antibodies of defined specificities [J].
Babcook, JS ;
Leslie, KB ;
Olsen, OA ;
Salmon, RA ;
Schrader, JW .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1996, 93 (15) :7843-7848
[5]
Identification of a 52 kb deletion downstream of the SOST gene in patients with van Buchem disease [J].
Balemans, W ;
Patel, N ;
Ebeling, M ;
Van Hul, E ;
Wuyts, W ;
Lacza, C ;
Dioszegi, M ;
Dikkers, FG ;
Hildering, P ;
Willems, PJ ;
Verheij, JBGM ;
Lindpaintner, K ;
Vickery, B ;
Foernzler, D ;
Van Hul, W .
JOURNAL OF MEDICAL GENETICS, 2002, 39 (02) :91-97
[6]
Increased bone density in sclerosteosis is due to the deficiency of a novel secreted protein (SOST) [J].
Balemans, W ;
Ebeling, M ;
Patel, N ;
Van Hul, E ;
Olson, P ;
Dioszegi, M ;
Lacza, C ;
Wuyts, W ;
Van den Ende, J ;
Willems, P ;
Paes-Alves, AF ;
Hill, S ;
Bueno, M ;
Ramos, FJ ;
Tacconi, P ;
Dikkers, FG ;
Stratakis, C ;
Lindpaintner, K ;
Vickery, B ;
Foernzler, D ;
Van Hul, W .
HUMAN MOLECULAR GENETICS, 2001, 10 (05) :537-543
[7]
WNT signaling in bone homeostasis and disease: from human mutations to treatments [J].
Baron, Roland ;
Kneissel, Michaela .
NATURE MEDICINE, 2013, 19 (02) :179-192
[8]
Once-yearly zoledronic acid for treatment of postmenopausal osteoporosis [J].
Black, Dennis M. ;
Delmas, Pierre D. ;
Eastell, Richard ;
Reid, Ian R. ;
Boonen, Steven ;
Cauley, Jane A. ;
Cosman, Felicia ;
Lakatos, Peter ;
Leung, Ping Chung ;
Man, Zulema ;
Mautalen, Carlos ;
Mesenbrink, Peter ;
Hu, Huilin ;
Caminis, John ;
Tong, Karen ;
Rosario-Jansen, Theresa ;
Krasnow, Joel ;
Hue, Trisha F. ;
Sellmeyer, Deborah ;
Eriksen, Erik Fink ;
Cummings, Steven R. .
NEW ENGLAND JOURNAL OF MEDICINE, 2007, 356 (18) :1809-1822
[9]
Bone dysplasia sclerosteosis results from loss of the SOST gene product, a novel cystine knot-containing protein [J].
Brunkow, ME ;
Gardner, JC ;
Van Ness, J ;
Paeper, BW ;
Kovacevich, BR ;
Proll, S ;
Skonier, JE ;
Zhao, L ;
Sabo, PJ ;
Fu, YH ;
Alisch, RS ;
Gillett, L ;
Colbert, T ;
Tacconi, P ;
Galas, D ;
Hamersma, H ;
Beighton, P ;
Mulligan, JT .
AMERICAN JOURNAL OF HUMAN GENETICS, 2001, 68 (03) :577-589
[10]
AMERICAN ASSOCIATION OF CLINICAL ENDOCRINOLOGISTS AND AMERICAN COLLEGE OF ENDOCRINOLOGY CLINICAL PRACTICE GUIDELINES FOR THE DIAGNOSIS AND TREATMENT OF POSTMENOPAUSAL OSTEOPOROSIS-2016 [J].
Camacho, Pauline M. ;
Petak, Steven M. ;
Binkley, Neil ;
Clarke, Bart L. ;
Harris, Steven T. ;
Hurley, Daniel L. ;
Kleerekoper, Michael ;
Lewiecki, E. Michael ;
Miller, Paul D. ;
Narula, Harmeet S. ;
Pessah-Pollack, Rachel ;
Tangpricha, Vin ;
Wimalawansa, Sunil J. ;
Watts, Nelson B. .
ENDOCRINE PRACTICE, 2016, 22 :1-42