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https://www.readbyqxmd.com/read/27920805/abaloparatide
#1
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
#2
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...
November 25, 2016: Bone
https://www.readbyqxmd.com/read/27859635/abaloparatide-is-an-anabolic-but-does-it-spare-resorption
#3
T J Martin, E Seeman
Abaloparatide is a novel peptide that shares aminoterminal sequence with PTHrP. It has been shown in a clinical trial to reduce vertebral and nonvertebral fracture risk and to promote bone formation in the aged osteopenic rat. It is proposed to produce its anabolic effect with less promotion of resorption than with teriparatide. This article is protected by copyright. All rights reserved.
November 18, 2016: 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
#4
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
#5
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...
October 17, 2016: 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
#6
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 1 (PTH1) receptor 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...
September 9, 2016: 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
#7
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
#8
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
#9
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...
July 9, 2016: Calcified Tissue International
https://www.readbyqxmd.com/read/27230847/-the-importance-of-teriparatide-in-the-treatment-of-osteoporosis
#10
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
#11
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
#12
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
#13
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
#14
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
https://www.readbyqxmd.com/read/26354487/emerging-therapies-for-osteoporosis
#15
REVIEW
Michael R McClung
Although several effective therapies are available for the treatment of osteoporosis in postmenopausal women and older men, there remains a need for the development of even more effective and acceptable drugs. Several new drugs that are in late-stage clinical development will be discussed. Abaloparatide (recombinant parathyroid hormone related peptide [PTHrP] analogue) has anabolic activity like teriparatide. Recent data from the phase 3 fracture prevention trial demonstrate that this agent is effective in reducing fracture risk...
December 2015: Endocrinology and Metabolism
https://www.readbyqxmd.com/read/26277199/novel-therapies-for-osteoporosis
#16
REVIEW
Polyzois Makras, Sideris Delaroudis, Athanasios D Anastasilakis
Since the identification of osteoporosis as a major health issue in aging populations and the subsequent development of the first treatment modalities for its management, considerable progress has been made in our understanding of the mechanisms controlling bone turnover and disease pathophysiology, thus enabling the pinpointing of new targets for intervention. This progress, along with advances in biotechnology, has rendered possible the development of ever more sophisticated treatments employing novel mechanisms of action...
October 2015: Metabolism: Clinical and Experimental
https://www.readbyqxmd.com/read/25987981/abaloparatide-a-new-anabolic-therapy-on-the-horizon
#17
Felicia Cosman
No abstract text is available yet for this article.
2015: BoneKEy Reports
https://www.readbyqxmd.com/read/25432357/future-directions-for-new-medical-entities-in-osteoporosis
#18
REVIEW
Serge Ferrari
Odanacatib, a selective cathepsin K inhibitor, decreases bone resorption, whereas osteoclast number increases and bone formation is maintained, perhaps even increased on some cortical surfaces. In a phase 2 clinical trial, post-menopausal women receiving odanacatib presented a sustained reduction of bone resorption markers, whereas procollagen type 1 N-terminal propeptide returned to normal. In turn areal bone mineral density increased continuously at both spine and hip for up to 5 years. Blosozumab and romosozumab are sclerostin neutralizing antibodies that exert potent anabolic effects on both trabecular and cortical compartments...
December 2014: Best Practice & Research. Clinical Endocrinology & Metabolism
https://www.readbyqxmd.com/read/25393645/effects-of-abaloparatide-a-human-parathyroid-hormone-related-peptide-analog-on-bone-mineral-density-in-postmenopausal-women-with-osteoporosis
#19
RANDOMIZED CONTROLLED TRIAL
Benjamin Z Leder, Louis St L O'Dea, José R Zanchetta, Prasana Kumar, Kathleen Banks, Kathleen McKay, C Richard Lyttle, Gary Hattersley
CONTEXT: Abaloparatide is a novel synthetic peptide analog of parathyroid hormone-related protein (PTHrP) that is currently being developed as a potential anabolic agent in the treatment of postmenopausal osteoporosis. OBJECTIVE: This study sought to assess the effects of abaloparatide on bone mineral density (BMD) at the lumbar spine, total hip, and femoral neck in postmenopausal women with osteoporosis. DESIGN: Multi-center, multi-national, double-blind placebo controlled trial in which postmenopausal women were randomly assigned to receive 24 weeks of treatment with daily sc injections of placebo, abaloparatide, 20, 40, or 80 μg, or teriparatide, 20 μg...
February 2015: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/25316089/investigational-parathyroid-hormone-receptor-analogs-for-the-treatment-of-osteoporosis
#20
REVIEW
Stergios A Polyzos, Polyzois Makras, Zoe Efstathiadou, Athanasios D Anastasilakis
INTRODUCTION: Intermittent parathyroid hormone (PTH) administration, acting through multiple signaling pathways, exerts an osteoanabolic effect on the skeleton that surpasses the effect of other antiosteoporotic agents. However, its efficacy is limited by the coupling effect and relatively common adverse events. Thus, the development of more sophisticated PTH receptor analogs seems imperative. AREAS COVERED: In this review, the authors summarize the role of PTH signaling pathway in bone remodeling...
February 2015: Expert Opinion on Investigational Drugs
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