Parathyroid hormone receptor agonists in the management of osteoporosis

Nicholas Fuggle^#¹, René Rizzoli^#², Charlotte Beaudart³, Bernard Cortet⁴, Elizabeth M Curtis¹, Mickaël Hiligsmann⁵, Jean-Marc Kaufman⁶, Nicola Veronese^{7

8}, Ben Hur Albergaria⁹, Nasser Al-Daghri⁷, Majed Alokail⁷, Maria Luisa Brandi^{10

11}, Olivier Bruyère¹², Nansa Burlet¹³, Claudia Campusano^{14

15}, Enrique Casado^{16

17}, Etienne Cavalier¹⁸, Manju Chandran^{19

20}, Cyrus Cooper^{1

21

22}, Patrizia D'Amelio²³, Bess Dawson-Hughes²⁴, Peter R Ebeling²⁵, John A Kanis²⁶, Andreas Kurth²⁷, Radmila Matijevic^{28

29}, Eugene McCloskey²⁶, Michael McClung³⁰, Ouafa Mkinsi³¹, Ngozi Njeze³², Régis P Radermecker³³, François Rannou³⁴, Stuart Silverman^{35

36}, Şansın Tüzün³⁷, Leith Zakraoui³⁸, Jean-Yves Reginster⁷, Nicholas C Harvey^{39

40}

Affiliations

¹ MRC Lifecourse Epidemiology Centre, University of Southampton, Southampton, UK.
² Division of Bone Diseases, Geneva University Hospitals and Faculty of Medicine, Geneva, Switzerland.
³ 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.
⁴ Department of Rheumatology, University-Hospital of Lille, Lille, France.
⁵ Department of Health Services Research, CAPHRI Care and Public Health Research Institute, Maastricht University, Maastricht, Netherlands.
⁶ Department of Endocrinology, Ghent University Hospital, Ghent, Belgium.
⁷ Biochemistry Department, College of Science, King Saud University, Riyadh, Kingdom of Saudi Arabia.
⁸ Saint Camillus International University of Health Sciences, Rome, Italy.
⁹ Espirito Santo Research and Osteoporosis Center, Federal University of Espirito Santo, Vitória, Brazil.
¹⁰ University Vita-Salute San Raffaele, Milan, Italy.
¹¹ FIRMO Foundation, Florence, Italy.
¹² Research Unit in Public Health, Epidemiology and Health Economics, University of Liège, Liège, Belgium.
¹³ The European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO), Liege, Belgium.
¹⁴ Department of Internal Medicine, Clínica Universidad de los Andes, Universidad de los Andes, Santiago, Chile.
¹⁵ School of Medicine, Universidad de los Andes, Santiago, Chile.
¹⁶ Department of Rheumatology, Parc Taulí Hospital Universitari, Universitat Autònoma de Barcelona, Sabadell, Spain.
¹⁷ Institut d'Investigació i Innovació Parc Taulí (I3PT-CERCA). Universitat Autònoma de Barcelona, Sabadell, Spain.
¹⁸ Department of Clinical Chemistry, CIRM, University of Liège, CHU de Liège, Liège, Belgium.
¹⁹ Osteoporosis and Bone Metabolism Unit, Department of Endocrinology, Singapore General Hospital, Singapore, Singapore.
²⁰ DUKE NUS Medical School, Singapore, Singapore.
²¹ NIHR Southampton Biomedical Research Centre, University of Southampton, Southampton, UK.
²² NIHR Oxford Biomedical Research Centre, University of Oxford, Oxford, UK.
²³ Department of Geriatrics and Geriatric Rehabilitation, Lausanne University Hospital, Lausanne, Switzerland.
²⁴ Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, Boston, MA, USA.
²⁵ Department of Medicine, School of Clinical Sciences, Monash University, Clayton, Victoria, Australia.
²⁶ Centre for Integrated Research in Musculoskeletal Ageing, Division of Clinical Medicine, School of Medicine and Population Health, University of Sheffield, Sheffield, UK.
²⁷ Johann Wolfgang Goethe University, Frankfurt, Germany.
²⁸ Faculty of Medicine, University of Novi Sad, Novi Sad, Serbia.
²⁹ Clinic for Orthopedic Surgery and Traumatology, University Clinical Center of Vojvodina, Novi Sad, Serbia.
³⁰ Oregon Osteoporosis Center, Portland, OR, US.
³¹ Rheumatology Department, Ibn Roch University Hospital, Casablanca, Morocco.
³² Department of Radiation Medicine, University of Nigeria Medical School, Nsukka, Nigeria.
³³ Department of Diabetes, Nutrition and Metabolic disorders, Clinical Pharmacology, University of Liège, CHU de Liège, Liège, Belgium.
³⁴ 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.
³⁵ OMC Clinical Research Center, Beverly Hills, CA, USA.
³⁶ Cedars-Sinai Medical Center, Beverly Hills, CA, USA.
³⁷ Department of Physical Medicine and Rehabilitation, Cerrahpaşa School of Medicine, Istanbul University-Cerrahpaşa, Istanbul, Turkey.
³⁸ Department of Rheumatology, University of Tunis El Manar, Tunis, Tunisia.
³⁹ MRC Lifecourse Epidemiology Centre, University of Southampton, Southampton, UK. nch@mrc.soton.ac.uk.
⁴⁰ NIHR Southampton Biomedical Research Centre, University of Southampton, Southampton, UK. nch@mrc.soton.ac.uk.

^# Contributed equally.

PMID: 40790089
DOI: 10.1038/s41584-025-01287-w

Review

Parathyroid hormone receptor agonists in the management of osteoporosis

Nicholas Fuggle et al. Nat Rev Rheumatol. 2025 Oct.

. 2025 Oct;21(10):599-611.

doi: 10.1038/s41584-025-01287-w. Epub 2025 Aug 11.

Authors

Affiliations

¹ MRC Lifecourse Epidemiology Centre, University of Southampton, Southampton, UK.
² Division of Bone Diseases, Geneva University Hospitals and Faculty of Medicine, Geneva, Switzerland.
³ 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.
⁴ Department of Rheumatology, University-Hospital of Lille, Lille, France.
⁵ Department of Health Services Research, CAPHRI Care and Public Health Research Institute, Maastricht University, Maastricht, Netherlands.
⁶ Department of Endocrinology, Ghent University Hospital, Ghent, Belgium.
⁷ Biochemistry Department, College of Science, King Saud University, Riyadh, Kingdom of Saudi Arabia.
⁸ Saint Camillus International University of Health Sciences, Rome, Italy.
⁹ Espirito Santo Research and Osteoporosis Center, Federal University of Espirito Santo, Vitória, Brazil.
¹⁰ University Vita-Salute San Raffaele, Milan, Italy.
¹¹ FIRMO Foundation, Florence, Italy.
¹² Research Unit in Public Health, Epidemiology and Health Economics, University of Liège, Liège, Belgium.
¹³ The European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO), Liege, Belgium.
¹⁴ Department of Internal Medicine, Clínica Universidad de los Andes, Universidad de los Andes, Santiago, Chile.
¹⁵ School of Medicine, Universidad de los Andes, Santiago, Chile.
¹⁶ Department of Rheumatology, Parc Taulí Hospital Universitari, Universitat Autònoma de Barcelona, Sabadell, Spain.
¹⁷ Institut d'Investigació i Innovació Parc Taulí (I3PT-CERCA). Universitat Autònoma de Barcelona, Sabadell, Spain.
¹⁸ Department of Clinical Chemistry, CIRM, University of Liège, CHU de Liège, Liège, Belgium.
¹⁹ Osteoporosis and Bone Metabolism Unit, Department of Endocrinology, Singapore General Hospital, Singapore, Singapore.
²⁰ DUKE NUS Medical School, Singapore, Singapore.
²¹ NIHR Southampton Biomedical Research Centre, University of Southampton, Southampton, UK.
²² NIHR Oxford Biomedical Research Centre, University of Oxford, Oxford, UK.
²³ Department of Geriatrics and Geriatric Rehabilitation, Lausanne University Hospital, Lausanne, Switzerland.
²⁴ Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, Boston, MA, USA.
²⁵ Department of Medicine, School of Clinical Sciences, Monash University, Clayton, Victoria, Australia.
²⁶ Centre for Integrated Research in Musculoskeletal Ageing, Division of Clinical Medicine, School of Medicine and Population Health, University of Sheffield, Sheffield, UK.
²⁷ Johann Wolfgang Goethe University, Frankfurt, Germany.
²⁸ Faculty of Medicine, University of Novi Sad, Novi Sad, Serbia.
²⁹ Clinic for Orthopedic Surgery and Traumatology, University Clinical Center of Vojvodina, Novi Sad, Serbia.
³⁰ Oregon Osteoporosis Center, Portland, OR, US.
³¹ Rheumatology Department, Ibn Roch University Hospital, Casablanca, Morocco.
³² Department of Radiation Medicine, University of Nigeria Medical School, Nsukka, Nigeria.
³³ Department of Diabetes, Nutrition and Metabolic disorders, Clinical Pharmacology, University of Liège, CHU de Liège, Liège, Belgium.
³⁴ 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.
³⁵ OMC Clinical Research Center, Beverly Hills, CA, USA.
³⁶ Cedars-Sinai Medical Center, Beverly Hills, CA, USA.
³⁷ Department of Physical Medicine and Rehabilitation, Cerrahpaşa School of Medicine, Istanbul University-Cerrahpaşa, Istanbul, Turkey.
³⁸ Department of Rheumatology, University of Tunis El Manar, Tunis, Tunisia.
³⁹ MRC Lifecourse Epidemiology Centre, University of Southampton, Southampton, UK. nch@mrc.soton.ac.uk.
⁴⁰ NIHR Southampton Biomedical Research Centre, University of Southampton, Southampton, UK. nch@mrc.soton.ac.uk.

^# Contributed equally.

PMID: 40790089
DOI: 10.1038/s41584-025-01287-w

Erratum in

Author Correction: Parathyroid hormone receptor agonists in the management of osteoporosis.
Fuggle N, Rizzoli R, Beaudart C, Cortet B, Curtis EM, Hiligsmann M, Kaufman JM, Veronese N, Albergaria BH, Al-Daghri N, Alokail M, Brandi ML, Bruyère O, Burlet N, Campusano C, Casado E, Cavalier E, Chandran M, Cooper C, D'Amelio P, Dawson-Hughes B, Ebeling PR, Kanis JA, Kurth A, Matijevic R, McCloskey E, McClung M, Mkinsi O, Njeze N, Radermecker RP, Rannou F, Silverman S, Tüzün Ş, Zakraoui L, Reginster JY, Harvey NC. Fuggle N, et al. Nat Rev Rheumatol. 2025 Sep 30. doi: 10.1038/s41584-025-01314-w. Online ahead of print. Nat Rev Rheumatol. 2025. PMID: 41028893 No abstract available.

Abstract

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.

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Conflict of interest statement

Competing interests: 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, Nestlè 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, Rubió, 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, Nestlé, 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’s 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.

References

1. Drake, M. T., Clarke, B. L. & Khosla, S. Bisphosphonates: mechanism of action and role in clinical practice. Mayo Clin. Proc. 83, 1032–1045 (2008). - PubMed
1. McClung, M. R. et al. Denosumab in postmenopausal women with low bone mineral density. N. Engl. J. Med. 354, 821–831 (2006). - PubMed
1. Riggs, B. L. & Hartmann, L. C. Selective estrogen-receptor modulators — mechanisms of action and application to clinical practice. N. Engl. J. Med. 348, 618–629 (2003). - PubMed
1. Rozenberg, S. et al. Is there a role for menopausal hormone therapy in the management of postmenopausal osteoporosis? Osteoporos. Int. 31, 2271–2286 (2020). - PubMed - PMC
1. Marino, S. & Bellido, T. PTH receptor signalling, osteocytes and bone disease induced by diabetes mellitus. Nat. Rev. Endocrinol. 20, 661–672 (2024). - PubMed

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Parathyroid hormone receptor agonists in the management of osteoporosis

Affiliations

Parathyroid hormone receptor agonists in the management of osteoporosis

Authors

Affiliations

Erratum in

Abstract

Conflict of interest statement

References

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Medical

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