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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/29048260/abaloparatide-comparator-trial-in-vertebral-endpoints-active-confirms-that-abaloparatide-is-a-valuable-addition-to-the-armamentarium-against-osteoporosis
#2
Jean-Yves Reginster, Nasser Mohammad Al Daghri, Olivier Bruyere
The recently published Abaloparatide Comparator Trial in Vertebral Endpoints (ACTIVE) assessed the efficacy and safety of abaloparatide (80 µg daily subcutaneous) (ABL) vs placebo during 18 months, in postmenopausal osteoporosis. Teriparatide (20 µg daily subcutaneous) (TPD) was used as an open label active comparator. The results of the study suggest that ABL increases bone mineral density more than TPD and reduces major osteoporotic fractures to a greater extent than TPD with a more rapid onset of action...
November 14, 2017: Expert Opinion on Pharmacotherapy
https://www.readbyqxmd.com/read/28914969/autocrine-and-paracrine-regulation-of-the-murine-skeleton-by-osteocyte-derived-parathyroid-hormone-related-protein
#3
Niloufar Ansari, Patricia Wm Ho, Blessing Crimeen-Irwin, Ingrid J Poulton, Athena R Brunt, Mark R Forwood, Paola Divieti Pajevic, Jonathan H Gooi, T John Martin, Natalie A Sims
Parathyroid hormone-related protein (PTHrP) and parathyroid hormone (PTH) have N-terminal domains that bind a common receptor, PTHR1. N-terminal PTH (teriparatide) and now a modified N-terminal PTHrP (abaloparatide) are US Food and Drug Administration (FDA)-approved therapies for osteoporosis. In physiology, PTHrP does not normally circulate at significant levels, but acts locally, and osteocytes, cells residing within the bone matrix, express both PTHrP and the PTHR1. Because PTHR1 in osteocytes is required for normal bone resorption, we determined how osteocyte-derived PTHrP influences the skeleton...
September 15, 2017: Journal of Bone and Mineral Research: the Official Journal of the American Society for Bone and Mineral Research
https://www.readbyqxmd.com/read/28836858/investigational-anabolic-agents-for-the-treatment-of-osteoporosis-an-update-on-recent-developments
#4
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/28780668/new-anabolic-therapies-for-osteoporosis
#5
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
#6
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/28743854/-new-methods-for-the-evaluation-of-bone-quality-bone-anabolic-agents-and-bone-quality
#7
Norio Yamamoto, Hiroyuki Tsuchiya
Teriparatide(TPTD)products that can be used clinically in Japan include a daily subcutaneous injection form produced by genetic engineering and a weekly subcutaneous injectable TPTD acetate form produced by chemical synthesis. Published reports indicate that both forms exhibit excellent antifracture efficacy, and as the only anabolic agents that promote osteogenesis, TPTD products now occupy a prominent position. However, the two forms differ considerably, not only in frequency of administration, but also in mechanism of action...
2017: Clinical Calcium
https://www.readbyqxmd.com/read/28680788/profile-of-abaloparatide-and-its-potential-in-the-treatment-of-postmenopausal-osteoporosis
#8
REVIEW
Sri Harsha Tella, Anuhya Kommalapati, Ricardo Correa
Abaloparatide (previously known as BA058) is a synthetic 34-amino acid peptide and novel selective activator of parathyroid hormone receptor 1 (PTHR1) currently under development as a new anabolic agent in the management of osteoporosis. This paper reviews the profile and potential of abaloparatide in the treatment of postmenopausal osteoporosis. This paper is based on clinical trials and a PubMed search. Search terms used were "abaloparatide", "BA058", and "PTHrP". This review outlines the effects of this anabolic PTHR1 activator, which increases bone mineral density in patients at high risk for osteoporosis...
May 31, 2017: Curēus
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
#9
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/28624872/abaloparatide-first-global-approval
#10
Matt Shirley
Abaloparatide (Tymlos™) is a synthetic peptide analogue of human parathyroid hormone-related protein that was developed by Radius Health as an osteoanabolic agent for the treatment of postmenopausal osteoporosis. Abaloparatide acts through selective activation of the parathyroid hormone type 1 receptor signalling pathway. In April 2017, subcutaneous abaloparatide received its first global approval, in the USA, for the treatment of postmenopausal women with osteoporosis at high risk for fracture, defined as a history of osteoporotic fracture, multiple risk factors for fracture, or patients who have failed or are intolerant to other available osteoporosis therapy...
August 2017: Drugs
https://www.readbyqxmd.com/read/28609423/abaloparatide-tymlos-for-postmenopausal-osteoporosis
#11
(no author information available yet)
No abstract text is available yet for this article.
June 19, 2017: Medical Letter on Drugs and Therapeutics
https://www.readbyqxmd.com/read/28529724/recent-advances-in-the-management-of-osteoporosis
#12
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
https://www.readbyqxmd.com/read/28474780/the-effect-of-abaloparatide-sc-on-fracture-risk-is-independent-of-baseline-frax-fracture-probability-a-post-hoc-analysis-of-the-active-study
#13
Eugene V McCloskey, Helena Johansson, Anders Oden, Nicholas C Harvey, Hai Jiang, Sara Modin, Lorraine Fitzpatrick, John A Kanis
Daily subcutaneous (SC) injections of the investigational drug abaloparatide-SC (80 mcg) for 18 months significantly decrease the risk of vertebral and nonvertebral fracture compared with placebo in postmenopausal women. We examined the efficacy of abaloparatide-SC as a function of baseline fracture risk, assessed using the FRAX tool. Baseline clinical risk factors (age, body mass index [BMI], prior fracture, glucocorticoid use, rheumatoid arthritis, and smoking) were entered into country-specific FRAX models to calculate the 10-year probability of major osteoporotic fractures, with or without femoral neck bone mineral density (BMD)...
August 2017: Journal of Bone and Mineral Research: the Official Journal of the American Society for Bone and Mineral Research
https://www.readbyqxmd.com/read/28389324/comparing-the-incidence-of-bone-tumors-in-rats-chronically-exposed%C3%A2-to-the-selective-pth-type-1-receptor-agonist-abaloparatide%C3%A2-or%C3%A2-pth-1-34
#14
Jacquelin Jolette, Bassem Attalla, Aurore Varela, Gerald G Long, Nacera Mellal, Sabile Trimm, Susan Y Smith, Michael S Ominsky, Gary Hattersley
Prolonged treatment with human parathyroid hormone (hPTH) in rats results in development of bone tumors, though this finding has not been supported by clinical experience. The PTH type 1 receptor agonist abaloparatide, selected for its bone anabolic activity, is under clinical development to treat postmenopausal women with osteoporosis. To determine the carcinogenic potential of abaloparatide, Fischer (F344) rats were administered SC daily abaloparatide at doses of 0, 10, 25, and 50 μg/kg or 30 μg/kg hPTH(1-34) as a positive control for up to 2 years...
April 4, 2017: Regulatory Toxicology and Pharmacology: RTP
https://www.readbyqxmd.com/read/28303448/parathyroid-hormone-and-parathyroid-hormone-related-protein-analogs-in-osteoporosis-therapy
#15
REVIEW
Benjamin Z Leder
PURPOSE OF REVIEW: The purpose is to review the efficacy and optimal use of parathyroid hormone and parathyroid hormone-related protein analogs in osteoporosis treatment. RECENT FINDINGS: The parathyroid hormone analog teriparatide, a potent stimulator of bone remodeling, increases hip and spine bone mineral density and reduces the risk of vertebral and non-vertebral fractures in postmenopausal osteoporotic women. The parathyroid hormone-related protein analog, abaloparatide, also reduces fracture incidence but has pharmacological effects that differ from teriparatide, particularly in cortical bone...
April 2017: Current Osteoporosis Reports
https://www.readbyqxmd.com/read/28286990/the-quest-for-new-drugs-to-prevent-osteoporosis-related-fractures
#16
REVIEW
T J de Villiers
There is a need for the development of new drugs to prevent osteoporosis-related fractures. Fractures are projected to increase and the present drugs have modest efficacy, significant side-effects and poor compliance. To illustrate the difficulties in the development of new drugs, the author reviews the fate of several drugs that have failed to gain regulatory approval. These drugs include arzoxifene, lasofoxifene, MK-5442, roncalceret and odanacatib. Romosozumab and abaloparatide are the only new drugs presently in phase-3 development...
April 2017: Climacteric: the Journal of the International Menopause Society
https://www.readbyqxmd.com/read/28160873/eighteen-months-of-treatment-with-subcutaneous-abaloparatide-followed-by-6-months-of-treatment-with-alendronate-in-postmenopausal-women-with-osteoporosis-results-of-the-activextend-trial
#17
RANDOMIZED CONTROLLED TRIAL
Felicia Cosman, Paul D Miller, Gregory C Williams, Gary Hattersley, Ming-Yi Hu, Ivo Valter, Lorraine A Fitzpatrick, Bente Juel Riis, Claus Christiansen, John P Bilezikian, Dennis Black
OBJECTIVE: To assess the efficacy and safety of 18 months of subcutaneous abaloparatide (ABL-SC) or placebo (PBO) followed by 6 months of alendronate (ALN) (preplanned interim analysis). PATIENTS AND METHODS: ACTIVExtend, an extension of ACTIVE, enrolled patients who completed 18 months of ABL-SC or PBO in ACTIVE to receive up to 24 additional months of open-label ALN; there was 1 month between the studies to re-consent patients. RESULTS: Of 1243 eligible ACTIVE patients, 1139 (92%) were enrolled in ACTIVExtend beginning November 20, 2012...
February 2017: Mayo Clinic Proceedings
https://www.readbyqxmd.com/read/28159062/abaloparatide-recombinant-human-pthrp-1-34-anabolic-therapy-for-osteoporosis
#18
REVIEW
Chee Kian Chew, Bart L Clarke
The treatment of osteoporosis is generally either by inhibition of bone resorption with antiresorptive agents or by stimulation of bone formation with anabolic agents. Currently, teriparatide (recombinant human parathyroid hormone 1-34 [rhPTH (1-34)]) is the only available approved anabolic agent in the U.S. Other anabolic agents are under investigation however. Abaloparatide is recombinant human parathyroid hormone-related peptide 1-34. This agent is an anabolic agent that appears more potent than teriparatide, and it may have more rapid onset of fracture reduction than teriparatide...
March 2017: Maturitas
https://www.readbyqxmd.com/read/28057953/daclizumab
#19
Anne P Kim, Danial E Baker
Each month, subscribers to The Formulary Monograph Service receive 5 to 6 well-documented monographs on drugs that are newly released or are in late phase 3 trials. The monographs are targeted to Pharmacy & Therapeutics Committees. Subscribers also receive monthly 1-page summary monographs on agents that are useful for agendas and pharmacy/nursing in-services. A comprehensive target drug utilization evaluation/medication use evaluation (DUE/MUE) is also provided each month. With a subscription, the monographs are are available online to subscribers...
December 2016: Hospital Pharmacy
https://www.readbyqxmd.com/read/28017957/-development-of-osteoporosis-drugs-the-past-the-present-and-the-future
#20
Shinya Tanaka
From 1990s to 2000s, new drugs for osteoporosis have been developed, and the bone metabolism researches have livened up. In those days, many a people gathered to the meeting from many countries, and the each booth of pharmaceutics was proud of its preeminence. The dedications by the society and its members have had osteoporosis diagnostics developed, the anchor drugs become prevalent, and the number of fractures reduced. Although the brilliant effects of Romosozumab and Abaloparatide were presented in the meeting held this year, the members had to accept the convergence state of new drug developments...
2017: Clinical Calcium
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