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https://www.readbyqxmd.com/read/29113980/management-of-endocrine-disease-novel-anabolic-treatments-for-osteoporosis
#1
Ernesto Canalis
Skeletal anabolic agents enhance bone formation, which is determined by the number and function of osteoblasts. Signals that influence the differentiation and function of cells of the osteoblast lineage play a role in the mechanism of action of anabolic agents in the skeleton. Wnts induce the differentiation of mesenchymal stem cells toward osteoblasts, and insulin-like growth factor I (IGF-I) enhances the function of mature osteoblasts. The activity of Wnt and IGF-I is controlled by proteins that bind to the growth factor or to its receptors...
November 7, 2017: European Journal of Endocrinology
https://www.readbyqxmd.com/read/29113523/monoclonal-antibodies-for-treating-osteoporosis
#2
Maria Felicia Faienza, Mariangela Chiarito, Gabriele D'amato, Graziana Colaianni, Silvia Colucci, Maria Grano, Giacomina Brunetti
Osteoporosis is the most widespread skeletal disease requiring innovative therapeutic strategies for its management. The understanding of receptor activator of nuclear factor kappa-B ligand (RANKL) and sclerostin's role in bone cell biology is completely changing the therapeutic landscape. RANKL supports osteoclast formation and activity and is mainly produced by cells of osteoblastic lineage. Sclerostin, an antagonist of the Wnt pathway, has a key role in bone formation and is mainly secreted by osteocytes...
November 7, 2017: Expert Opinion on Biological Therapy
https://www.readbyqxmd.com/read/29079995/bone-targeted-therapies-in-cancer-induced-bone-disease
#3
REVIEW
Sofia Sousa, Philippe Clézardin
Cancer-induced bone disease is a major source of morbidity and mortality in cancer patients. Thus, effective bone-targeted therapies are essential to improve disease-free, overall survival and quality of life of cancer patients with bone metastases. Depending of the cancer-type, bone metastases mainly involve the modulation of osteoclast and/or osteoblast activity by tumour cells. To inhibit metastatic bone disease effectively, it is imperative to understand its underlying mechanisms and identify the target cells for therapy...
October 27, 2017: Calcified Tissue International
https://www.readbyqxmd.com/read/29027994/bone-diseases-romosozumab-on-track-or-derailed
#4
Sundeep Khosla
No abstract text is available yet for this article.
December 2017: Nature Reviews. Endocrinology
https://www.readbyqxmd.com/read/28892459/romosozumab-promising-or-practice-changing
#5
EDITORIAL
Clifford J Rosen
New England Journal of Medicine, Volume 377, Issue 15, Page 1479-1480, October 2017.
October 12, 2017: New England Journal of Medicine
https://www.readbyqxmd.com/read/28892457/romosozumab-or-alendronate-for-fracture-prevention-in-women-with-osteoporosis
#6
RANDOMIZED CONTROLLED TRIAL
Kenneth G Saag, Jeffrey Petersen, Maria Luisa Brandi, Andrew C Karaplis, Mattias Lorentzon, Thierry Thomas, Judy Maddox, Michelle Fan, Paul D Meisner, Andreas Grauer
BACKGROUND: Romosozumab is a monoclonal antibody that binds to and inhibits sclerostin, increases bone formation, and decreases bone resorption. METHODS: We enrolled 4093 postmenopausal women with osteoporosis and a fragility fracture and randomly assigned them in a 1:1 ratio to receive monthly subcutaneous romosozumab (210 mg) or weekly oral alendronate (70 mg) in a blinded fashion for 12 months, followed by open-label alendronate in both groups. The primary end points were the cumulative incidence of new vertebral fracture at 24 months and the cumulative incidence of clinical fracture (nonvertebral and symptomatic vertebral fracture) at the time of the primary analysis (after clinical fractures had been confirmed in ≥330 patients)...
October 12, 2017: New England Journal of Medicine
https://www.readbyqxmd.com/read/28854619/amgen-and-ucb-announce-increased-cardiovascular-risk-in-patients-receiving-romosozumab-an-anti-sclerotin-antibody
#7
(no author information available yet)
No abstract text is available yet for this article.
August 1, 2017: Rheumatology
https://www.readbyqxmd.com/read/28836858/investigational-anabolic-agents-for-the-treatment-of-osteoporosis-an-update-on-recent-developments
#8
REVIEW
Anastasia D Dede, Polyzois Makras, Athanasios D Anastasilakis
Teriparatide, a PTH analogue, was the first anabolic agent to be approved for the treatment of osteoporosis in 2002. Abaloparatide was also recently approved by the FDA. The need for other anabolic agents is still unmet. Areas covered: In this review, we discuss target molecules and recent advances in the field of anabolic therapy for osteoporosis. PTH and PTHrP analogues binding to the PTH receptor and different routes of administration of teriparatide to avoid the burden of daily subcutaneous injections are discussed...
October 2017: Expert Opinion on Investigational Drugs
https://www.readbyqxmd.com/read/28794512/osteoporosis-romosozumab-versus-teriparatide
#9
Dario Ummarino
No abstract text is available yet for this article.
September 2017: Nature Reviews. Rheumatology
https://www.readbyqxmd.com/read/28780668/new-anabolic-therapies-for-osteoporosis
#10
REVIEW
Salvatore Minisola, Cristiana Cipriani, Marco Occhiuto, Jessica Pepe
Osteoporosis is characterized by low bone mass and qualitative structural abnormalities of bone tissue, leading to increased bone fragility that results in fractures. Pharmacological therapy is aimed at decreasing the risk of fracture, mainly correcting the imbalance between bone resorption and formation at the level of bone remodeling units. Anabolic therapy has the capability to increase bone mass to a greater extent than traditional antiresorptive agents. The only currently available drug licensed is parathyroid hormone 1-34 (teriparatide); new drugs are on the horizon, targeting the stimulation of bone formation, and therefore improving bone mass, structure and ultimately skeletal strength...
August 5, 2017: Internal and Emergency Medicine
https://www.readbyqxmd.com/read/28756709/emerging-anabolic-agents-in-the-treatment-of-osteoporosis
#11
REVIEW
Christina Lovato, E Michael Lewiecki
Osteoporosis is a common skeletal disease with serious consequences due to osteoporotic fractures and high costs to society for post-fracture care. Most patients at high risk for fracture are not receiving care to reduce fracture risk. The osteoporosis treatment gap has reached crisis proportions. Strategies to reduce the treatment gap include systematic methods for identifying and treating high risk patients, better education of patients and healthcare providers, better use of currently available drugs, and development of new drugs to treat osteoporosis...
September 2017: Expert Opinion on Emerging Drugs
https://www.readbyqxmd.com/read/28755782/romosozumab-sclerostin-monoclonal-antibody-versus-teriparatide-in-postmenopausal-women-with-osteoporosis-transitioning-from-oral-bisphosphonate-therapy-a-randomised-open-label-phase-3-trial
#12
Bente L Langdahl, Cesar Libanati, Daria B Crittenden, Michael A Bolognese, Jacques P Brown, Nadia S Daizadeh, Eva Dokoupilova, Klaus Engelke, Joel S Finkelstein, Harry K Genant, Stefan Goemaere, Lars Hyldstrup, Esteban Jodar-Gimeno, Tony M Keaveny, David Kendler, Peter Lakatos, Judy Maddox, Jorge Malouf, Fabio E Massari, Jose Fernando Molina, Maria Rosa Ulla, Andreas Grauer
BACKGROUND: Previous bisphosphonate treatment attenuates the bone-forming effect of teriparatide. We compared the effects of 12 months of romosozumab (AMG 785), a sclerostin monoclonal antibody, versus teriparatide on bone mineral density (BMD) in women with postmenopausal osteoporosis transitioning from bisphosphonate therapy. METHODS: This randomised, phase 3, open-label, active-controlled study was done at 46 sites in North America, Latin America, and Europe...
September 30, 2017: Lancet
https://www.readbyqxmd.com/read/28731148/molecular-genetics-and-targeted-therapy-of-wnt-related-human-diseases-review
#13
Masuko Katoh, Masaru Katoh
Canonical WNT signaling through Frizzled and LRP5/6 receptors is transduced to the WNT/β-catenin and WNT/stabilization of proteins (STOP) signaling cascades to regulate cell fate and proliferation, whereas non-canonical WNT signaling through Frizzled or ROR receptors is transduced to the WNT/planar cell polarity (PCP), WNT/G protein-coupled receptor (GPCR) and WNT/receptor tyrosine kinase (RTK) signaling cascades to regulate cytoskeletal dynamics and directional cell movement. WNT/β-catenin signaling cascade crosstalks with RTK/SRK and GPCR-cAMP-PKA signaling cascades to regulate β-catenin phosphorylation and β-catenin-dependent transcription...
September 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28689769/osteoporosis-treatment-recent-developments-and-ongoing-challenges
#14
REVIEW
Sundeep Khosla, Lorenz C Hofbauer
Osteoporosis is an enormous and growing public health problem. Once considered an inevitable consequence of ageing, it is now eminently preventable and treatable. Ironically, despite tremendous therapeutic advances, there is an increasing treatment gap for patients at high fracture risk. In this Series paper, we trace the evolution of drug therapy for osteoporosis, which began in the 1940s with the demonstration by Fuller Albright that treatment with oestrogen could reverse the negative calcium balance that developed in women after menopause or oophorectomy...
July 6, 2017: Lancet Diabetes & Endocrinology
https://www.readbyqxmd.com/read/28687496/romosozumab-increases-bone-mineral-density-in-postmenopausal-japanese-women-with-osteoporosis-a-phase-2-study
#15
Hideaki Ishibashi, Daria B Crittenden, Akimitsu Miyauchi, Cesar Libanati, Judy Maddox, Michelle Fan, Li Chen, Andreas Grauer
BACKGROUND: Romosozumab is a monoclonal antibody that inhibits sclerostin and rapidly increases bone mineral density (BMD) through a dual effect on bone by increasing bone formation and decreasing bone resorption, as shown in a global phase 2 study in postmenopausal women with low bone mass. Here, we report the key results of a phase 2, double-blind, placebo-controlled, dose-ranging study to assess the efficacy and safety of romosozumab in postmenopausal Japanese women with osteoporosis...
July 5, 2017: Bone
https://www.readbyqxmd.com/read/28629610/a-model-for-assessing-the-clinical-and-economic-benefits-of-bone-forming-agents-for-reducing-fractures-in-postmenopausal-women-at-high-near-term-risk-of-osteoporotic-fracture
#16
Claire E O'Hanlon, Anju Parthan, Morgan Kruse, Shannon Cartier, Bjorn Stollenwerk, Yawen Jiang, John P Caloyeras, Daria B Crittenden, Richard Barron
PURPOSE: The goal of this study was to assess and compare the potential clinical and economic value of emerging bone-forming agents using the only currently available agent, teriparatide, as a reference case in patients at high, near-term (imminent, 1- to 2-year) risk of osteoporotic fractures, extending to a lifetime horizon with sequenced antiresorptive agents for maintenance treatment. METHODS: Analyses were performed by using a Markov cohort model accounting for time-specific fracture protection effects of bone-forming agents followed by antiresorptive treatment with denosumab...
July 2017: Clinical Therapeutics
https://www.readbyqxmd.com/read/28547661/targeting-sclerostin-in-postmenopausal-osteoporosis-focus-on-romosozumab-and-blosozumab
#17
Ian R Reid
Most current treatments for osteoporosis inhibit bone resorption and reduce total fracture numbers by about one-quarter. The identification of the osteocytic protein sclerostin as a potent regulator of bone turnover and bone density has led to the development of a new therapeutic class-agents that inhibit sclerostin activity, resulting in increased bone formation and reduced bone resorption. Romosozumab and blosozumab are monoclonal antibodies that bind to sclerostin, reducing its inhibition of Wnt signaling...
May 25, 2017: BioDrugs: Clinical Immunotherapeutics, Biopharmaceuticals and Gene Therapy
https://www.readbyqxmd.com/read/28543940/greater-gains-in-spine-and-hip-strength-for-romosozumab-compared-with-teriparatide-in-postmenopausal-women-with-low-bone-mass
#18
Tony M Keaveny, Daria B Crittenden, Michael A Bolognese, Harry K Genant, Klaus Engelke, Beatriz Oliveri, Jacques P Brown, Bente L Langdahl, Chris Yan, Andreas Grauer, Cesar Libanati
Romosozumab is a monoclonal antibody that inhibits sclerostin and has been shown to reduce the risk of fractures within 12 months. In a phase II, randomized, placebo-controlled clinical trial of treatment-naïve postmenopausal women with low bone mass, romosozumab increased bone mineral density (BMD) at the hip and spine by the dual effect of increasing bone formation and decreasing bone resorption. In a substudy of that trial, which included placebo and teriparatide arms, here we investigated whether those observed increases in BMD also resulted in improvements in estimated strength, as assessed by finite element analysis...
May 25, 2017: Journal of Bone and Mineral Research: the Official Journal of the American Society for Bone and Mineral Research
https://www.readbyqxmd.com/read/28540603/positioning-novel-biologicals-in-ckd-mineral-and-bone-disorders
#19
REVIEW
Lida Tartaglione, Marzia Pasquali, Silverio Rotondi, Maria Luisa Muci, Adrian Covic, Sandro Mazzaferro
Renal osteodystrophy (ROD), the histologic bone lesions of chronic kidney disease (CKD), is now included in a wider syndrome with laboratory abnormalities of mineral metabolism and extra-skeletal calcifications or CKD-mineral and bone disorders (CKD-MBD), to highlight the increased burden of mortality. Aging people, frequently identified as early CKD, could suffer from either the classical age-related osteoporosis (OP) or ROD. Distinguishing between these two bone diseases may not be easy without bone biopsy...
October 2017: Journal of Nephrology
https://www.readbyqxmd.com/read/28529724/recent-advances-in-the-management-of-osteoporosis
#20
REVIEW
Seiji Fukumoto, Toshio Matsumoto
There has been substantial progress in the management of patients with osteoporosis and the prevention of osteoporotic fractures. Currently available strong anti-resorptive agents are bisphosphonates and an anti-receptor activator of nuclear factor-kappa B ligand (RANKL) antibody, denosumab. Although bisphosphonates and denosumab both inhibit bone resorption and prevent vertebral and non-vertebral fractures, their mechanisms of action are different. Whereas bisphosphonates' effects on bone mineral density and fracture peak around 3 to 5 years and become plateaued, those of denosumab are maintained for up to 10 years...
2017: F1000Research
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