abaloparatide; Parathyroid Hormone-Related Protein; Teriparatide; Bone Density Conservation Agents; Receptor, Parathyroid Hormone, Type 1; Humans; Bone Density/drug effects; Osteoporotic Fractures/prevention & control; Parathyroid Hormone-Related Protein/therapeutic use; Teriparatide/therapeutic use; Osteoporosis/drug therapy; Bone Density Conservation Agents/therapeutic use; Receptor, Parathyroid Hormone, Type 1/agonists; Bone Density; Osteoporosis; Osteoporotic Fractures; Rheumatology
Abstract :
[en] Parathyroid hormone (PTH) regulates bone homeostasis. Intermittent exposure to PTH results in bone formation being greater than bone resorption, and this effect has been harnessed through the development of agonists of the PTH and PTH-related protein type 1 receptor (PTH1R) to treat osteoporosis. Teriparatide, an analogue of the first 34 amino acids of PTH, and abaloparatide, which resembles PTH-related protein (PTHrP) in structure, are PTH1R agonists currently in clinical use. Both medications have been shown to increase bone mineral density at the lumbar spine, femoral neck and total hip. Randomized controlled trials with teriparatide or abaloparatide have also provided evidence of reduction in vertebral and non-vertebral fractures. The ACTIVE trial suggested slightly greater efficacy for major osteoporotic fractures (as an exploratory end point) for abaloparatide than for teriparatide. A similar potential superiority was suggested for hip fracture in a real-world, observational study. Side effects of these medications are usually transient, and although a risk of osteosarcoma was suggested by studies using murine models, no such risk has been observed in extensive human studies. Overall, both teriparatide and abaloparatide have demonstrated convincing clinical effectiveness and cost-effectiveness, with a reassuring safety profile. Potential differences in their effects on bone mineral density and their antifracture effects offer avenues for differentiation but require further validation in appropriately designed studies.
Disciplines :
Laboratory medicine & medical technology Public health, health care sciences & services
Author, co-author :
Fuggle, Nicholas ; MRC Lifecourse Epidemiology Centre, University of Southampton, Southampton, UK
Rizzoli, René ; Université de Liège - ULiège > Département des sciences de la santé publique > Santé publique, Epidémiologie et Economie de la santé ; Division of Bone Diseases, Geneva University Hospitals and Faculty of Medicine, Geneva, Switzerland
Beaudart, Charlotte ; Université de Liège - ULiège > Département des sciences de la santé publique > Epidémiologie générale ; Public Health Aging Research & Epidemiology (PHARE) Group, Research Unit in Clinical Pharmacology and Toxicology (URPC), NAmur Research Institute for LIfe Sciences (NARILIS), University of Namur, Namur, Belgium
Cortet, Bernard; Department of Rheumatology, University-Hospital of Lille, Lille, France
Curtis, Elizabeth M; MRC Lifecourse Epidemiology Centre, University of Southampton, Southampton, UK
Hiligsmann, Mickaël ; Université de Liège - ULiège > Département des sciences de la santé publique > Santé publique, Epidémiologie et Economie de la santé ; Department of Health Services Research, CAPHRI Care and Public Health Research Institute, Maastricht University, Maastricht, Netherlands
Kaufman, Jean-Marc ; Université de Liège - ULiège > Département des sciences de la santé publique > Santé publique, Epidémiologie et Economie de la santé ; Department of Endocrinology, Ghent University Hospital, Ghent, Belgium
Veronese, Nicola ; Biochemistry Department, College of Science, King Saud University, Riyadh, Kingdom of Saudi Arabia ; Saint Camillus International University of Health Sciences, Rome, Italy
Albergaria, Ben Hur; Espirito Santo Research and Osteoporosis Center, Federal University of Espirito Santo, Vitória, Brazil
Al-Daghri, Nasser ; Université de Liège - ULiège > Département des sciences de la santé publique > Santé publique, Epidémiologie et Economie de la santé ; Biochemistry Department, College of Science, King Saud University, Riyadh, Kingdom of Saudi Arabia
Alokail, Majed; Biochemistry Department, College of Science, King Saud University, Riyadh, Kingdom of Saudi Arabia
Brandi, Maria Luisa ; University Vita-Salute San Raffaele, Milan, Italy ; FIRMO Foundation, Florence, Italy
Bruyère, Olivier ; Université de Liège - ULiège > Département des sciences de la santé publique > Santé publique, Epidémiologie et Economie de la santé
Burlet, Nansa ; Université de Liège - ULiège > Département des sciences de la santé publique > Santé publique, Epidémiologie et Economie de la santé ; The European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO), Liege, Belgium
Campusano, Claudia; Department of Internal Medicine, Clínica Universidad de los Andes, Universidad de los Andes, Santiago, Chile ; School of Medicine, Universidad de los Andes, Santiago, Chile
Casado, Enrique ; Department of Rheumatology, Parc Taulí Hospital Universitari, Universitat Autònoma de Barcelona, Sabadell, Spain ; Institut d'Investigació i Innovació Parc Taulí (I3PT-CERCA). Universitat Autònoma de Barcelona, Sabadell, Spain
Cavalier, Etienne ; Université de Liège - ULiège > Département de pharmacie > Chimie médicale
Chandran, Manju; Osteoporosis and Bone Metabolism Unit, Department of Endocrinology, Singapore General Hospital, Singapore, Singapore ; DUKE NUS Medical School, Singapore, Singapore
Cooper, Cyrus ; Université de Liège - ULiège > Département des sciences de la santé publique > Santé publique, Epidémiologie et Economie de la santé ; MRC Lifecourse Epidemiology Centre, University of Southampton, Southampton, UK ; NIHR Southampton Biomedical Research Centre, University of Southampton, Southampton, UK ; NIHR Oxford Biomedical Research Centre, University of Oxford, Oxford, UK
D'Amelio, Patrizia; Department of Geriatrics and Geriatric Rehabilitation, Lausanne University Hospital, Lausanne, Switzerland
Dawson-Hughes, Bess; Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, Boston, MA, USA
Ebeling, Peter R ; Department of Medicine, School of Clinical Sciences, Monash University, Clayton, Victoria, Australia
Kanis, John A; Centre for Integrated Research in Musculoskeletal Ageing, Division of Clinical Medicine, School of Medicine and Population Health, University of Sheffield, Sheffield, UK
Kurth, Andreas; Johann Wolfgang Goethe University, Frankfurt, Germany
Matijevic, Radmila; Faculty of Medicine, University of Novi Sad, Novi Sad, Serbia ; Clinic for Orthopedic Surgery and Traumatology, University Clinical Center of Vojvodina, Novi Sad, Serbia
McCloskey, Eugene ; Centre for Integrated Research in Musculoskeletal Ageing, Division of Clinical Medicine, School of Medicine and Population Health, University of Sheffield, Sheffield, UK
McClung, Michael; Oregon Osteoporosis Center, Portland, OR, US
Mkinsi, Ouafa; Rheumatology Department, Ibn Roch University Hospital, Casablanca, Morocco
Njeze, Ngozi; Department of Radiation Medicine, University of Nigeria Medical School, Nsukka, Nigeria
Radermecker, Régis ; Université de Liège - ULiège > Département des sciences cliniques > Pharmacologie clinique
Rannou, François ; Université de Liège - ULiège > Département des sciences de la santé publique > Santé publique, Epidémiologie et Economie de la santé ; Service de Rééducation et de Réadaptation de l'Appareil Locomoteur et des Pathologies du Rachis, Hôpital Cochin, Assistance publique - hôpitaux de Paris, Centre-Université Paris Cité, Paris, France
Silverman, Stuart; OMC Clinical Research Center, Beverly Hills, CA, USA ; Cedars-Sinai Medical Center, Beverly Hills, CA, USA
Tüzün, Şansın; Department of Physical Medicine and Rehabilitation, Cerrahpaşa School of Medicine, Istanbul University-Cerrahpaşa, Istanbul, Turkey
Zakraoui, Leith; Department of Rheumatology, University of Tunis El Manar, Tunis, Tunisia
Reginster, Jean-Yves ; Université de Liège - ULiège > Département des sciences de la santé publique ; Biochemistry Department, College of Science, King Saud University, Riyadh, Kingdom of Saudi Arabia
Harvey, Nicholas C ; MRC Lifecourse Epidemiology Centre, University of Southampton, Southampton, UK. nch@mrc.soton.ac.uk ; NIHR Southampton Biomedical Research Centre, University of Southampton, Southampton, UK. nch@mrc.soton.ac.uk
N.F. has received honoraria and speaker fees from UCB and Viatris, and travel bursaries from Eli Lilly and Pfizer. B.C. has received occasional fees as an expert or speaker from Alexion, Amgen, Aptissen, Expanscience, Lilly, Kyowa Kirin, Novartis, Theramex, UCB and Viatris. E.M.C. has received speaker fees from Eli Lilly, Thornton and Ross, and UCB, and travel bursaries or conference support from Amgen and Eli Lilly. M.H. has received research grants (paid to his institution) from Angelini Pharma and Radius Health, and lecture fees from IBSA (paid to his institution) and Mylan Pharmaceuticals, and was grant adviser for Pfizer (paid to his institution). N.V. declares personal fees from Bayer, Fidia, Nestl\u00E8 and Viatris. B.H.A. reports research grants from Amgen and UCB, and honoraria from Amgen, Theramex and UCB. M.L.B. declares honoraria from Amgen, Ascendis, Bruno Farmaceutici, Calcilytix and Kyowa Kirin, grants or speaker fees from Alexion, Amgen, Amolyt, Bruno Farmaceutici, CoGeDi, Echolight, Gedeon Richter, Kyowa Kirin, Monte Rosa Therapeutics and UCB, and consultancy for Aboca, Alexion, Amolyt, Bruno Farmaceutici, Calcilytix, Echolight, Enterabio, Kyowa Kirin, Personal Genomics and Septern. O.B. has received consulting or lecture fees from Amgen, Aptissen, Biophytis, IBSA, Mylan, Novartis, Nutricia, Orifarm, Sanofi, UCB and Viatris outside the submitted work. E. Casado has received honoraria and speaker fees from FAES, Gedeon-Richter, STADA, Theramex and UCB, and travel bursaries from Amgen, Rubi\u00F3, STADA and Theramex. M.C. has received honoraria and travel grants from Amgen and Promedius AI solutions. P.D'A. declares research grants and honoraria from ErreKappa, Nestl\u00E9, OM Pharma and Schwabe Pharma. P.R.E. declares research grants from Amgen, Alexion and Sanofi, and honoraria from Amgen, Alexion and Kyowa Kirin. J.A.K. is a director of Osteoporosis Research, which maintains FRAX. A.K. declares honoraria for scientific advisory board, research grants and speakers fees from AgNovos bioscience, Alexion, Amgen, Celltrion Deutschland, Echolight, Eli Lilly, Ipsen, Imaging Biopsy Lab (IBL), Kyowa Kirin, Merit Medical, new4med, Novartis, NovoNordisk, Roche, Sandoz, Servier, Stadapharm, Theramex and UCB. E.McC. is a director of Osteoporosis Research, which maintains FRAX, and has also received honoraria and research funding from Amgen, Fresenius Kabi, Lilly, ObsEva, Radius Pharma, Theramex and UCB. M.McC. declares consulting fees or honoraria from Amgen, Alexion, Pfizer and UCB. O.M. declares lecture fees or honoraria from Bottu Johnson and Johnson, Pfizer and Sanofi. J.-Y.R. declares speaker\u2019s Bureau for Radius Health and Theramex, and consultancy agreement for Theramex. N.C.H. has received personal fees, consultancy, lecture fees or honoraria from Alliance for Better Bone Health, AMGEN, MSD, Eli Lilly, Internis Pharma, Kyowa Kirin, Servier, Shire, Consilient Healthcare, Theramex and UCB outside the submitted work. R.R., C.B., J.-M.K, N.A.-D., M.A., N.B., C. Campusano, E. Cavalier, C. Cooper, B.D.-H., R.M., N.N., R.P. R., F.R., S.S. S.T., and L.Z. have no competing interests to declare.This ESCEO Working Group was funded by the ESCEO. The ESCEO receives unrestricted educational grants to support its educational and scientific activities from non-governmental organisations, not-for-profit organisations, non-commercial or corporate partners. The choice of topics, participants, content and agenda of the Working Groups as well as the writing, editing, submission and reviewing of the manuscript are the sole responsibility of the ESCEO, without any influence from third parties. This work was supported by the Distinguished Scientist Fellowship Program (DSFP) of the King Saud University, Riyadh, Kingdom of Saudi Arabia.
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