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https://www.readbyqxmd.com/read/28303448/parathyroid-hormone-and-parathyroid-hormone-related-protein-analogs-in-osteoporosis-therapy
#1
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...
March 16, 2017: Current Osteoporosis Reports
https://www.readbyqxmd.com/read/28286990/the-quest-for-new-drugs-to-prevent-osteoporosis-related-fractures
#2
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
#3
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
#4
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
#5
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
#6
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
https://www.readbyqxmd.com/read/27920805/abaloparatide
#7
REVIEW
Stefano Gonnelli, Carla Caffarelli
Abaloparatide is an investigational analog of human PTHrP (1-34) being developed for the treatment of osteoporosis. The amino-acid sequence of abaloparatide is identical to that of PTHrP in the first 20 amino-acids, while over half of the remaining amino-acids are different. Some studies in animals and in humans reported that abaloparatide presented a potent anabolic activity with reduced effects on bone resorption as compared to that observed with teriparatide. This may be due to a more transient signaling response of abaloparatide related to differing affinities of the two drugs to the specific conformations of the PTH1 receptor...
May 2016: Clinical Cases in Mineral and Bone Metabolism
https://www.readbyqxmd.com/read/27894941/one-year-of-abaloparatide-a-selective-peptide-activator-of-the-pth1-receptor-increased-bone-mass-and-strength-in-ovariectomized-rats
#8
Aurore Varela, Luc Chouinard, Elisabeth Lesage, Robert Guldberg, Susan Y Smith, Paul J Kostenuik, Gary Hattersley
Abaloparatide is a novel 34 amino acid peptide selected to be a potent and selective activator of the parathyroid hormone receptor 1 (PTHR1) signaling pathway. The effects of 12months of abaloparatide treatment on bone mass, bone strength and bone quality was assessed in osteopenic ovariectomized (OVX) rats. SD rats were subjected to OVX or sham surgery at 6months of age and left untreated for 3months to allow OVX-induced bone loss. Eighteen OVX rats were sacrificed after this bone depletion period, and the remaining OVX rats received daily s...
February 2017: Bone
https://www.readbyqxmd.com/read/27859635/abaloparatide-is-an-anabolic-but-does-it-spare-resorption
#9
T John Martin, Ego Seeman
No abstract text is available yet for this article.
January 2017: Journal of Bone and Mineral Research: the Official Journal of the American Society for Bone and Mineral Research
https://www.readbyqxmd.com/read/27826127/effects-of-abaloparatide-sc-ba058-on-bone-histology-and-histomorphometry-the-active-phase-3-trial
#10
Carolina Moreira, Lorraine A Fitzpatrick, Yamei Wang, Robert R Recker
There are a number of effective treatments for osteoporosis but most are in the antiresorptive class of compounds. Abaloparatide-SC is a new osteoanabolic agent, which increased bone mineral density and lowered the risk of osteoporosis-related fractures in the phase 3 ACTIVE trial. The objective of this report is to describe the effects of abaloparatide-SC 80μg on bone histology and histomorphometry in iliac crest bone biopsies from this trial in which participants were randomized to receive blinded daily subcutaneous injections of placebo or abaloparatide-SC 80μg/d or open-label teriparatide 20μg/d for 18months...
November 5, 2016: Bone
https://www.readbyqxmd.com/read/27748532/one-year-of-abaloparatide-a-selective-activator-of-the-pth1-receptor-increased-bone-formation-and-bone-mass-in-osteopenic-ovariectomized-rats-without-increasing-bone-resorption
#11
Aurore Varela, Luc Chouinard, Elisabeth Lesage, Susan Y Smith, Gary Hattersley
Abaloparatide is a novel 34-amino acid peptide selected to be a potent and selective activator of the parathyroid hormone receptor (PTH1R) signaling pathway with 41% homology to PTH(1-34) and 76% homology to PTHrP(1-34). A 12-month treatment study was conducted in osteopenic ovariectomized (OVX) rats to characterize the mechanisms by which abaloparatide increases bone mass. Sprague-Dawley (SD) rats were subjected to OVX or sham surgery at age 6 months and left untreated for 3 months to allow OVX-induced bone loss...
January 2017: Journal of Bone and Mineral Research: the Official Journal of the American Society for Bone and Mineral Research
https://www.readbyqxmd.com/read/27612281/effects-of-abaloparatide-sc-on-fractures-and-bone-mineral-density-in-subgroups-of-postmenopausal-women-with-osteoporosis-and-varying-baseline-risk-factors
#12
Felicia Cosman, Gary Hattersley, Ming-Yi Hu, Gregory C Williams, Lorraine A Fitzpatrick, Dennis M Black
Abaloparatide-SC is a novel 34-amino acid peptide created to be a potent and selective activator of the parathyroid hormone receptor type 1 (PTHR1) signaling pathway. In the Abaloparatide Comparator Trial in Vertebral Endpoints (ACTIVE) Phase 3 trial (NCT01343004), abaloparatide reduced new morphometric vertebral fractures by 86% compared with placebo (p < 0.001) and nonvertebral fractures by 43% (p = 0.049) in postmenopausal women with osteoporosis. Abaloparatide-SC increased bone mineral density (BMD) 3...
January 2017: Journal of Bone and Mineral Research: the Official Journal of the American Society for Bone and Mineral Research
https://www.readbyqxmd.com/read/27533157/effect-of-abaloparatide-vs-placebo-on-new-vertebral-fractures-in-postmenopausal-women-with-osteoporosis-a-randomized-clinical-trial
#13
RANDOMIZED CONTROLLED TRIAL
Paul D Miller, Gary Hattersley, Bente Juel Riis, Gregory C Williams, Edith Lau, Luis Augusto Russo, Peter Alexandersen, Cristiano A F Zerbini, Ming-yi Hu, Alan G Harris, Lorraine A Fitzpatrick, Felicia Cosman, Claus Christiansen
IMPORTANCE: Additional therapies are needed for prevention of osteoporotic fractures. Abaloparatide is a selective activator of the parathyroid hormone type 1 receptor. OBJECTIVE: To determine the efficacy and safety of abaloparatide, 80 μg, vs placebo for prevention of new vertebral fracture in postmenopausal women at risk of osteoporotic fracture. DESIGN, SETTING, AND PARTICIPANTS: The Abaloparatide Comparator Trial In Vertebral Endpoints (ACTIVE) was a phase 3, double-blind, RCT (March 2011-October 2014) at 28 sites in 10 countries...
August 16, 2016: JAMA: the Journal of the American Medical Association
https://www.readbyqxmd.com/read/27510350/osteoporosis-treatment-a-missed-opportunity
#14
Frances Milat, Peter R Ebeling
Osteoporosis affects 1.2 million Australians and, in 2012, fractures due to osteoporosis and osteopenia in Australians aged over 50 years cost $2.75 billion. Even minor minimal trauma fractures are associated with increased morbidity and mortality. Despite increasing therapeutic options for managing osteoporosis, fewer than 20% of patients with a minimal trauma fracture are treated or investigated for osteoporosis, so under-treatment is extremely common. Fracture risk assessment is important for selecting patients who require specific anti-osteoporosis therapy...
August 15, 2016: Medical Journal of Australia
https://www.readbyqxmd.com/read/27395059/six-weeks-of-daily-abaloparatide-treatment-increased-vertebral-and-femoral-bone-mineral-density-microarchitecture-and-strength-in-ovariectomized-osteopenic-rats
#15
Hila Bahar, Kyla Gallacher, Julie Downall, Carol A Nelson, Maysoun Shomali, Gary Hattersley
Abaloparatide is a novel, potent and selective activator of parathyroid hormone receptor 1 (PTHR1) under clinical development for the treatment of osteoporosis. We assessed the effect of 6 weeks of abaloparatide on bone mass, microarchitecture, quality and strength in ovariectomized (OVX) rats. After 8 weeks of post-surgical bone depletion (baseline), OVX rats (n = 20-21/group) received daily subcutaneous vehicle (OVX-Veh) or abaloparatide at 5 or 20 µg/kg. Sham-operated control rats (n = 24) received vehicle...
November 2016: Calcified Tissue International
https://www.readbyqxmd.com/read/27230847/-the-importance-of-teriparatide-in-the-treatment-of-osteoporosis
#16
Mika Yamauchi
The anabolic agent teriparatide (TPTD) clearly increases bone mineral density both in daily and weekly formulations. In addition, the effectiveness of daily TPTD in reducing the risks of vertebral and non-vertebral fractures and of weekly TPTD in reducing the risk of vertebral fractures has been established. TPTD is indicated for severe osteoporosis, such as cases of multiple fractures, hip fractures, and fractures sustained during antiresorptive therapy. TPTD has also been shown to be effective for male osteoporosis and glucocorticoid-induced osteoporosis...
June 2016: Clinical Calcium
https://www.readbyqxmd.com/read/26989807/new-horizons-in-osteoporosis-therapies
#17
REVIEW
Torben Harsløf, Bente L Langdahl
Efficient therapies are available for the treatment of osteoporosis, however, there are still unmet needs. Anti-resorptive therapies only increase bone mineral density to a certain extent and reduce the risk of non-vertebral fractures by 20%, only one anabolic option is available-the effect of which levels off over time, and the evidence for combination therapy targeting both resorption and formation is limited. The current review will focus on emerging treatments of osteoporosis with the potential of enhanced anabolic effects (romosozumab and abaloparatide) or uncoupling of resorption and formation (odanacatib and romosozumab) as well as the effect of combination therapy...
June 2016: Current Opinion in Pharmacology
https://www.readbyqxmd.com/read/26946704/-bone-diseases
#18
Brigitte Uebelhart, René Rizzoli
Calcium intake shows a small impact on bone mineral density and fracture risk. Denosumab is a more potent inhibitor of bone resorption than zoledronate. Abaloparatide, PTHrP analog, increases bone mineral density and decreases fracture incidence. Teriparatide could be delivered via a transdermic device. Romosozumab and odanacatib improve calculated bone strength. Sequential or combined treatments with denosumab and teriparatide could be of interest, but not denosumab followed by teriparatide. Fibrous dysplasia, Paget disease and hypophosphatasia are updated, as well as atypical femoral fracture and osteonecrosis of the jaw...
January 13, 2016: Revue Médicale Suisse
https://www.readbyqxmd.com/read/26944033/commentary-concurrent-administration-of-pth-and-antiresorptives-additive-effects-or-dxa-cosmetics
#19
EDITORIAL
Erik Fink Eriksen, Jacques P Brown
Osteoanabolic therapy with parathyroid hormone (PTH(1-84)) or the PTH analogues teriparatide (PTH(1-34), TPTD) and abaloparatide induces a positive remodeling balance and increases modeling and remodeling activity on bone surfaces. As the anabolic action of PTH is primarily remodeling based increased bone turnover maximizes bone accrual. Increased remodeling, however, also increases cortical porosity and reduces mineralization of newly formed bone, which may cause initial reductions in BMD, particularly at sites rich in cortical bone...
May 2016: Bone
https://www.readbyqxmd.com/read/26562265/binding-selectivity-of-abaloparatide-for-pth-type-1-receptor-conformations-and-effects-on-downstream-signaling
#20
COMPARATIVE STUDY
Gary Hattersley, Thomas Dean, Braden A Corbin, Hila Bahar, Thomas J Gardella
The PTH receptor type 1 (PTHR1) mediates the actions of two endogenous polypeptide ligands, PTH and PTHrP, and thereby plays key roles in bone biology. Based on its capacity to stimulate bone formation, the peptide fragment PTH (1-34) is currently in use as therapy for osteoporosis. Abaloparatide (ABL) is a novel synthetic analog of human PTHrP (1-34) that holds promise as a new osteoporosis therapy, as studies in animals suggest that it can stimulate bone formation with less of the accompanying bone resorption and hypercalcemic effects that can occur with PTH (1-34)...
January 2016: Endocrinology
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