NEW TREATMENT MODALITIES IN OSTEOPOROSIS

被引:24
作者
Canalis, Ernesto [1 ]
机构
[1] Univ Connecticut, Sch Med, Farmington, CT USA
关键词
BONE-MINERAL DENSITY; GROWTH-FACTOR-I; CATHEPSIN-K; POSTMENOPAUSAL WOMEN; PARATHYROID-HORMONE; TARGETED DISRUPTION; STRONTIUM RANELATE; VERTEBRAL FRACTURE; DOUBLE-BLIND; SRC KINASE;
D O I
10.4158/EP10048.RA
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Objective: To describe recently discovered agents for the management of osteoporosis. Methods: A literature review (PubMed search) was conducted to identify agents at various stages of development for osteoporosis treatment. Agents under study or review for approval were included. Results: In menopause, bone remodeling is increased, and agents that suppress bone resorption can stabilize bone mass. In contrast, agents that target the osteoblast can increase bone formation and bone mass. Novel antiresorptive agents can target the formation or the activity of osteoclasts. They include denosumab, an antibody to receptor activated nuclear factor kappa B; new selective estrogen receptor modulators, such as bazedoxifene; and cathepsin K inhibitors, such as odanacatib. Src kinase inhibitors are in the early phases of development. Parathyroid hormone is the only approved anabolic agent for the treatment of osteoporosis. Novel anabolic therapies for osteoporosis may include the use of factors with anabolic properties for bone or the neutralization of growth factor antagonists. Recent discoveries have demonstrated that the Wnt/beta-catenin signaling pathway has a central role in osteoblastic cell differentiation. Antibodies to Wnt antagonists, such as sclerostin, are under development as new therapeutic approaches for osteoporosis. Anabolic therapies have the potential to enhance bone mass, but their long-term safety must be proven. Conclusions: New developments in the treatment of osteoporosis include novel antiresorptive and anabolic agents. Their success will depend on their long-term effectiveness and safety profile. (Endocr Pract. 2010;16:855-863)
引用
收藏
页码:855 / 863
页数:9
相关论文
共 68 条
[41]   Wnt inhibitory factor 1 is epigenetically silenced in human osteosarcoma, and targeted disruption accelerates osteosarcomagenesis in mice [J].
Kansara, Maya ;
Tsang, Michael ;
Kodjabachian, Laurent ;
Sims, Natalie A. ;
Trivett, Melanie K. ;
Ehrich, Mathias ;
Dobrovic, Alexander ;
Slavin, John ;
Choong, Peter F. M. ;
Simmons, Paul J. ;
Dawid, Igor B. ;
Thomas, David M. .
JOURNAL OF CLINICAL INVESTIGATION, 2009, 119 (04) :837-851
[42]   Increasing Options for the Treatment of Osteoporosis [J].
Khosla, Sundeep .
NEW ENGLAND JOURNAL OF MEDICINE, 2009, 361 (08) :818-820
[43]   Proteasome inhibitors: from research tools to drug candidates [J].
Kisselev, AF ;
Goldberg, AL .
CHEMISTRY & BIOLOGY, 2001, 8 (08) :739-758
[44]   Regulation of bone mass by Wnt signaling [J].
Krishnan, V ;
Bryant, HU ;
MacDougald, OA .
JOURNAL OF CLINICAL INVESTIGATION, 2006, 116 (05) :1202-1209
[45]   A highly potent inhibitor of cathepsin K (relacatib) reduces biomarkers of bone resorption both in vitro and in an acute model of elevated bone turnover in vivo in monkeys [J].
Kumar, S. ;
Dare, L. ;
Vasko-Moser, J. A. ;
James, I. E. ;
Blake, S. M. ;
Rickard, D. J. ;
Hwang, S. -M. ;
Tomaszek, T. ;
Yamashita, D. S. ;
Marquis, R. W. ;
Oh, H. ;
Jeong, J. U. ;
Veber, D. F. ;
Gowen, M. ;
Lark, M. W. ;
Stroup, G. .
BONE, 2007, 40 (01) :122-131
[46]   Association between insulin-like growth factor I and bone mineral density in older women and men: The Framingham Heart Study [J].
Langlois, JA ;
Rosen, CJ ;
Visser, M ;
Hannan, MT ;
Harris, T ;
Wilson, PWF ;
Kiel, DP .
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 1998, 83 (12) :4257-4262
[47]   INSULIN-LIKE GROWTH-FACTORS AND CANCER [J].
LEROITH, D ;
BASERGA, R ;
HELMAN, L ;
ROBERTS, CT .
ANNALS OF INTERNAL MEDICINE, 1995, 122 (01) :54-59
[48]   Mice lacking cathepsin K maintain bone remodeling but develop bone fragility despite high bone mass [J].
Li, Chao Yang ;
Jepsen, Karl J. ;
Majeska, Robert J. ;
Zhang, Jian ;
Ni, Rujing ;
Gelb, Bruce D. ;
Schaffler, Mitchell B. .
JOURNAL OF BONE AND MINERAL RESEARCH, 2006, 21 (06) :865-875
[49]   Targeted deletion of the sclerostin gene in mice results in increased bone formation and bone strength [J].
Li, Xiaodong ;
Ominsky, Michael S. ;
Niu, Qing-Tian ;
Sun, Ning ;
Daugherty, Betsy ;
D'Agostin, Diane ;
Kurahara, Carole ;
Gao, Yongming ;
Cao, Jin ;
Gong, Jianhua ;
Asuncion, Frank ;
Barrero, Mauricio ;
Warmington, Kelly ;
Dwyer, Denise ;
Stolina, Marina ;
Morony, Sean ;
Sarosi, Ildiko ;
Kostenuik, Paul J. ;
Lacey, David L. ;
Simonet, W. Scott ;
Ke, Hua Zhu ;
Paszty, Chris .
JOURNAL OF BONE AND MINERAL RESEARCH, 2008, 23 (06) :860-869
[50]   Sclerostin Antibody Treatment Increases Bone Formation, Bone Mass, and Bone Strength in a Rat Model of Postmenopausal Osteoporosis [J].
Li, Xiaodong ;
Ominsky, Michael S. ;
Warmington, Kelly S. ;
Morony, Sean ;
Gong, Jianhua ;
Cao, Jin ;
Gao, Yongming ;
Shalhoub, Victoria ;
Tipton, Barbara ;
Haldankar, R. J. ;
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 .
JOURNAL OF BONE AND MINERAL RESEARCH, 2009, 24 (04) :578-588