Status of drug development for the prevention and treatment of osteoporosis

被引:24
作者
Schwarz, Peter [1 ,3 ]
Jorgensen, Niklas Rye [2 ,3 ]
Abrahamsen, Bo [1 ,4 ]
机构
[1] Copenhagen Univ Hosp, Res Ctr Ageing & Osteoporosis, Dept Med, DK-2600 Glostrup, Denmark
[2] Copenhagen Univ Hosp, Res Ctr Ageing & Osteoporosis, Dept Diagnost, DK-2600 Glostrup, Denmark
[3] Univ Copenhagen, Fac Hlth Sci, Glostrup, Denmark
[4] Univ Southern Denmark, Glostrup, Denmark
关键词
cathepsin K; odanacatib; osteoporosis; postmenopausal; romosozumab; sclerostin-neutralizing monoclonal antibody; treatment; BONE-MINERAL DENSITY; PARATHYROID-HORMONE; 1-34; SENSING RECEPTOR ANTAGONIST; VERTEBRAL FRACTURE RISK; J-SHAPED ASSOCIATION; ALL-CAUSE MORTALITY; POSTMENOPAUSAL WOMEN; STRONTIUM RANELATE; SEQUENTIAL CITRATE; SCLEROSTIN ANTIBODY;
D O I
10.1517/17460441.2014.884067
中图分类号
R9 [药学];
学科分类号
100702 [药剂学];
摘要
Introduction: The metabolic bone disease osteoporosis is a growing health and health-economic problem worldwide. Bisphosphonates are the most widely used antiresorptive medication and the de facto gold standard in fracture prophylaxis all over the world, in conjunction with calcium and vitamin D supplementation. Several new medications for the treatment of postmenopausal osteoporosis are in the pipeline. Areas covered: The authors present the most recent studies on new and current antiresorptive as well as anabolic drugs. Specifically, the authors present the current knowledge on drugs directed against cathepsin K and sclerostin as well as the new pathways of interest from preclinical studies. Expert opinion: New scientific results have identified novel signaling pathways as potential targets for future development of anti-osteoporotic drugs. The treatments close to marketing at the moment are odanacatib and romosozumab and these are both promising new medications based on bone mineral density results, safety profile and administration. Theoretically, romosozumab may hold the potential to be a drug to 'cure' even advanced stages of osteoporosis with short-term treatment. However, safety, fracture data and cost are key elements that will determine the extent of use.
引用
收藏
页码:245 / 253
页数:9
相关论文
共 71 条
[1]
Nationwide registry-based analysis of cardiovascular risk factors and adverse outcomes in patients treated with strontium ranelate [J].
Abrahamsen, B. ;
Grove, E. L. ;
Vestergaard, P. .
OSTEOPOROSIS INTERNATIONAL, 2014, 25 (02) :757-762
[2]
Abrahamsen B, 2013, OSTEOPOROSI IN PRESS
[3]
Activin A Suppresses Osteoblast Mineralization Capacity by Altering Extracellular Matrix (ECM) Composition and Impairing Matrix Vesicle (MV) Production [J].
Alves, Rodrigo D. A. M. ;
Eijken, Marco ;
Bezstarosti, Karel ;
Demmers, Jeroen A. A. ;
van Leeuwen, Johannes P. T. M. .
MOLECULAR & CELLULAR PROTEOMICS, 2013, 12 (10) :2890-2900
[4]
Circulating activin-A is elevated in postmenopausal women with low bone mass: the three-month effect of zoledronic acid treatment [J].
Anastasilakis, A. D. ;
Polyzos, S. A. ;
Makras, P. ;
Gkiomisi, A. ;
Savvides, M. ;
Papatheodorou, A. ;
Terpos, E. .
OSTEOPOROSIS INTERNATIONAL, 2013, 24 (07) :2127-2132
[5]
A soluble bone morphogenetic protein type IA receptor increases bone mass and bone strength [J].
Baud'huin, Marc ;
Solban, Nicolas ;
Cornwall-Brady, Milton ;
Sako, Dianne ;
Kawamoto, Yoshimi ;
Liharska, Katia ;
Lath, Darren ;
Bouxsein, Mary L. ;
Underwood, Kathryn W. ;
Ucran, Jeffrey ;
Kumar, Ravindra ;
Pobre, Eileen ;
Grinberg, Asya ;
Seehra, Jasbir ;
Canalis, Ernesto ;
Pearsall, R. Scott ;
Croucher, Peter I. .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2012, 109 (30) :12207-12212
[6]
A Pooled Analysis of Vitamin D Dose Requirements for Fracture Prevention [J].
Bischoff-Ferrari, Heike A. ;
Willett, Walter C. ;
Orav, Endel J. ;
Lips, Paul ;
Meunier, Pierre J. ;
Lyons, Ronan A. ;
Flicker, Leon ;
Wark, John ;
Jackson, Rebecca D. ;
Cauley, Jane A. ;
Meyer, Haakon E. ;
Pfeifer, Michael ;
Sanders, Kerrie M. ;
Stahelin, Hannes B. ;
Theiler, Robert ;
Dawson-Hughes, Bess .
NEW ENGLAND JOURNAL OF MEDICINE, 2012, 367 (01) :40-49
[7]
The effects of parathyroid hormone and alendronate alone or in combination in postmenopausal osteoporosis [J].
Black, DM ;
Greenspan, SL ;
Ensrud, KE ;
Palermo, L ;
McGowan, JA ;
Lang, TF ;
Garnero, P ;
Bouxsein, ML ;
Bilezikian, JP ;
Rosen, CJ .
NEW ENGLAND JOURNAL OF MEDICINE, 2003, 349 (13) :1207-1215
[8]
Randomised trial of effect of alendronate on risk of fracture in women with existing vertebral fractures [J].
Black, DM ;
Cummings, SR ;
Karpf, DB ;
Cauley, JA ;
Thompson, DE ;
Nevitt, MC ;
Bauer, DC ;
Genant, HK ;
Haskell, WL ;
Marcus, R ;
Ott, SM ;
Torner, JC ;
Quandt, SA ;
Reiss, TF ;
Ensrud, KE .
LANCET, 1996, 348 (9041) :1535-1541
[9]
Blum B, 2004, ORTHOPEDICS, V27, pS161
[10]
The Effect of Three or Six Years of Denosumab Exposure in Women With Postmenopausal Osteoporosis: Results From the FREEDOM Extension [J].
Bone, Henry G. ;
Chapurlat, Roland ;
Brandi, Maria-Luisa ;
Brown, Jacques P. ;
Czerwinski, Edward ;
Krieg, Marc-Antoine ;
Mellstrom, Dan ;
Radominski, Sebastiao C. ;
Reginster, Jean-Yves ;
Resch, Heinrich ;
Roman Ivorra, Jose A. ;
Roux, Christian ;
Vittinghoff, Eric ;
Daizadeh, Nadia S. ;
Wang, Andrea ;
Bradley, Michelle N. ;
Franchimont, Nathalie ;
Geller, Michelle L. ;
Wagman, Rachel B. ;
Cummings, Steven R. ;
Papapoulos, Socrates .
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 2013, 98 (11) :4483-4492