Pub Date : 2025-09-09DOI: 10.1038/s41584-025-01298-7
Ahmet Gül, Ivona Aksentijevich, Paul Brogan, Marco Gattorno, Peter C. Grayson, Seza Ozen
{"title":"Reply to ‘Inborn errors of immunity and AAV: a complex picture’","authors":"Ahmet Gül, Ivona Aksentijevich, Paul Brogan, Marco Gattorno, Peter C. Grayson, Seza Ozen","doi":"10.1038/s41584-025-01298-7","DOIUrl":"10.1038/s41584-025-01298-7","url":null,"abstract":"","PeriodicalId":18810,"journal":{"name":"Nature Reviews Rheumatology","volume":"21 12","pages":"753-753"},"PeriodicalIF":32.7,"publicationDate":"2025-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145017624","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-09-08DOI: 10.1038/s41584-025-01297-8
Axel Finckh
Analysis of regional variations in the epidemiology of rheumatoid arthritis (RA) over the past 40 years indicates that the age-standardized incidence of RA has increased — and is expected to continue rising — while the mortality and morbidity of the disease are decreasing. As a result, the number of years lived with disability and the overall disease burden attributable to RA have increased and are projected to rise further.
{"title":"The epidemiology of RA","authors":"Axel Finckh","doi":"10.1038/s41584-025-01297-8","DOIUrl":"10.1038/s41584-025-01297-8","url":null,"abstract":"Analysis of regional variations in the epidemiology of rheumatoid arthritis (RA) over the past 40 years indicates that the age-standardized incidence of RA has increased — and is expected to continue rising — while the mortality and morbidity of the disease are decreasing. As a result, the number of years lived with disability and the overall disease burden attributable to RA have increased and are projected to rise further.","PeriodicalId":18810,"journal":{"name":"Nature Reviews Rheumatology","volume":"21 12","pages":"701-702"},"PeriodicalIF":32.7,"publicationDate":"2025-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145017914","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-09-08DOI: 10.1038/s41584-025-01294-x
Jörg H. W. Distler, Masataka Kuwana, Shervin Assassi, Christopher P. Denton
Systemic sclerosis (SSc) is an autoimmune disease in which fibrotic, vascular, autoimmune and fibrotic mechanisms synergize to promote disease progression. SSc is associated with high morbidity and mortality, primarily owing to fibrotic tissue remodelling and subsequent organ failure. Despite progress with the approval of novel therapies, mortality remains high; approximately half of the people diagnosed with SSc will succumb to disease. This statistic highlights the considerable need for novel, effective therapies. Indeed, SSc has become a disease with very active drug development. Numerous drugs with different modes of actions are currently evaluated in or are about to enter clinical trials in SSc. These clinical trials provide hope for effectively slowing or even halting the progression of fibrosis and thereby further improving outcomes for patients with SSc. This Review provides a comprehensive overview of emerging therapies for the treatment of systemic sclerosis. The authors highlight novel therapeutic targets and emphasize the need for precision medicine approaches for the effective treatment of this disease.
{"title":"Emerging therapies for the treatment of systemic sclerosis","authors":"Jörg H. W. Distler, Masataka Kuwana, Shervin Assassi, Christopher P. Denton","doi":"10.1038/s41584-025-01294-x","DOIUrl":"10.1038/s41584-025-01294-x","url":null,"abstract":"Systemic sclerosis (SSc) is an autoimmune disease in which fibrotic, vascular, autoimmune and fibrotic mechanisms synergize to promote disease progression. SSc is associated with high morbidity and mortality, primarily owing to fibrotic tissue remodelling and subsequent organ failure. Despite progress with the approval of novel therapies, mortality remains high; approximately half of the people diagnosed with SSc will succumb to disease. This statistic highlights the considerable need for novel, effective therapies. Indeed, SSc has become a disease with very active drug development. Numerous drugs with different modes of actions are currently evaluated in or are about to enter clinical trials in SSc. These clinical trials provide hope for effectively slowing or even halting the progression of fibrosis and thereby further improving outcomes for patients with SSc. This Review provides a comprehensive overview of emerging therapies for the treatment of systemic sclerosis. The authors highlight novel therapeutic targets and emphasize the need for precision medicine approaches for the effective treatment of this disease.","PeriodicalId":18810,"journal":{"name":"Nature Reviews Rheumatology","volume":"21 10","pages":"612-625"},"PeriodicalIF":32.7,"publicationDate":"2025-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145009244","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-09-05DOI: 10.1038/s41584-025-01301-1
Holly Webster
Findings indicate that the collagen-binding integrin α11 could be a therapeutic target for rheumatoid arthritis.
提示胶原结合整合素α11可能成为类风湿关节炎的治疗靶点。
{"title":"Integrin α11 on fibroblast-like synoviocytes promotes joint damage in arthritis","authors":"Holly Webster","doi":"10.1038/s41584-025-01301-1","DOIUrl":"10.1038/s41584-025-01301-1","url":null,"abstract":"Findings indicate that the collagen-binding integrin α11 could be a therapeutic target for rheumatoid arthritis.","PeriodicalId":18810,"journal":{"name":"Nature Reviews Rheumatology","volume":"21 10","pages":"577-577"},"PeriodicalIF":32.7,"publicationDate":"2025-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144995350","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-09-05DOI: 10.1038/s41584-025-01300-2
Maria Papatriantafyllou
Stem-like and effector-like peripheral helper T cells have distinct functions in rheumatoid arthritis.
干细胞样和效应样外周辅助性T细胞在类风湿关节炎中具有不同的功能。
{"title":"Two subsets of TPH cells with distinct functions in RA","authors":"Maria Papatriantafyllou","doi":"10.1038/s41584-025-01300-2","DOIUrl":"10.1038/s41584-025-01300-2","url":null,"abstract":"Stem-like and effector-like peripheral helper T cells have distinct functions in rheumatoid arthritis.","PeriodicalId":18810,"journal":{"name":"Nature Reviews Rheumatology","volume":"21 10","pages":"577-577"},"PeriodicalIF":32.7,"publicationDate":"2025-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144995349","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-09-01DOI: 10.1038/s41584-025-01291-0
Deepak A. Rao
Methods for high-dimensional immune-cell profiling have advanced dramatically in the past decade. Studies of tissue and blood samples from patients with rheumatic diseases have revealed stereotyped features of immune dysregulation in individual diseases and in subsets of patients who share diagnosis of a heterogeneous disease. Translating immunological patterns into clinically implementable, actionable biomarkers has the potential to improve detection and quantification of pathological immune activity and selection of appropriate treatments for autoimmune rheumatic diseases. For example, cytometric features can be used to distinguish the various forms of inflammatory arthritis, stratify subsets of patients with rheumatoid arthritis or subsets of patients with systemic lupus erythematosus and predict treatment responses. Cellular immune profiling also enables the identification of specific features of immune dysregulation in individuals with rare, undiagnosed, inflammatory diseases. Several paths might lead to translation of discoveries from broad immune profiling into clinical tests to interrogate immune activation in people with rheumatic diseases. In this Review article, the potential of cytometry- and single-cell RNA sequencing-based immune profiling for aiding the diagnosis and personalized treatment of rheumatic diseases is discussed.
{"title":"Immune-cell profiling to guide stratification and treatment of patients with rheumatic diseases","authors":"Deepak A. Rao","doi":"10.1038/s41584-025-01291-0","DOIUrl":"10.1038/s41584-025-01291-0","url":null,"abstract":"Methods for high-dimensional immune-cell profiling have advanced dramatically in the past decade. Studies of tissue and blood samples from patients with rheumatic diseases have revealed stereotyped features of immune dysregulation in individual diseases and in subsets of patients who share diagnosis of a heterogeneous disease. Translating immunological patterns into clinically implementable, actionable biomarkers has the potential to improve detection and quantification of pathological immune activity and selection of appropriate treatments for autoimmune rheumatic diseases. For example, cytometric features can be used to distinguish the various forms of inflammatory arthritis, stratify subsets of patients with rheumatoid arthritis or subsets of patients with systemic lupus erythematosus and predict treatment responses. Cellular immune profiling also enables the identification of specific features of immune dysregulation in individuals with rare, undiagnosed, inflammatory diseases. Several paths might lead to translation of discoveries from broad immune profiling into clinical tests to interrogate immune activation in people with rheumatic diseases. In this Review article, the potential of cytometry- and single-cell RNA sequencing-based immune profiling for aiding the diagnosis and personalized treatment of rheumatic diseases is discussed.","PeriodicalId":18810,"journal":{"name":"Nature Reviews Rheumatology","volume":"21 11","pages":"657-670"},"PeriodicalIF":32.7,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144923904","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-08-26DOI: 10.1038/s41584-025-01290-1
David S. Pisetsky, Amanda M. Eudy, Jennifer L. Rogers, Ru-Rong Ji, Katherine T. Martucci, Camilla Svensson, Peter E. Lipsky
Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by protean clinical manifestations that are associated with immune system dysregulation. Of these manifestations, pain and pain-related symptoms such as fatigue, mood disturbance and cognitive impairment are the most common features reported by patients and represent important determinants of quality of life. Nevertheless, the relationship of these symptoms to underlying immune mechanisms is unclear. To advance scientific study and patient-centric care, this Review will consider the origin of pain in SLE and the clinical ramifications. Although many of the inflammatory aspects of SLE, including arthritis, serositis and skin disease, can be associated with nociceptive pain, patients frequently report pain that seems out of proportion to the degree of inflammation. In many of these patients, pain might reflect central and peripheral nervous system sensitization that mediates nociplasticity, a change in brain processing; with nociplasticity, changes in neuronal function and brain connections can amplify the experience of pain and pain-related symptoms. The close interplay between the immune and the nervous systems means that widespread pain and the associated symptoms can be considered as essential features of SLE; these features might share pathogenic mechanisms with other autoimmune diseases and nociplastic pain syndromes such as fibromyalgia. In systemic lupus erythematosus (SLE), pain is one of the most commonly reported and debilitating symptoms. The authors of this Review highlight the importance of understanding the mechanisms of pain in SLE and addressing pain and pain-associated symptoms in the management of SLE.
{"title":"Pain in systemic lupus erythematosus: emerging insights and paradigms","authors":"David S. Pisetsky, Amanda M. Eudy, Jennifer L. Rogers, Ru-Rong Ji, Katherine T. Martucci, Camilla Svensson, Peter E. Lipsky","doi":"10.1038/s41584-025-01290-1","DOIUrl":"10.1038/s41584-025-01290-1","url":null,"abstract":"Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by protean clinical manifestations that are associated with immune system dysregulation. Of these manifestations, pain and pain-related symptoms such as fatigue, mood disturbance and cognitive impairment are the most common features reported by patients and represent important determinants of quality of life. Nevertheless, the relationship of these symptoms to underlying immune mechanisms is unclear. To advance scientific study and patient-centric care, this Review will consider the origin of pain in SLE and the clinical ramifications. Although many of the inflammatory aspects of SLE, including arthritis, serositis and skin disease, can be associated with nociceptive pain, patients frequently report pain that seems out of proportion to the degree of inflammation. In many of these patients, pain might reflect central and peripheral nervous system sensitization that mediates nociplasticity, a change in brain processing; with nociplasticity, changes in neuronal function and brain connections can amplify the experience of pain and pain-related symptoms. The close interplay between the immune and the nervous systems means that widespread pain and the associated symptoms can be considered as essential features of SLE; these features might share pathogenic mechanisms with other autoimmune diseases and nociplastic pain syndromes such as fibromyalgia. In systemic lupus erythematosus (SLE), pain is one of the most commonly reported and debilitating symptoms. The authors of this Review highlight the importance of understanding the mechanisms of pain in SLE and addressing pain and pain-associated symptoms in the management of SLE.","PeriodicalId":18810,"journal":{"name":"Nature Reviews Rheumatology","volume":"21 10","pages":"626-639"},"PeriodicalIF":32.7,"publicationDate":"2025-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144905872","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-08-14DOI: 10.1038/s41584-025-01295-w
Elizabeth C. Rosser, Lucy R. Wedderburn
The future of rheumatology research will be defined by the growing era of personalized and stratified medicine, with a focus on establishing drug-free remission. In the face of substantial global upheaval, now is the time to ensure no patient group is left behind by prioritizing research equity and inclusion.
{"title":"Looking to the new horizon in rheumatology research","authors":"Elizabeth C. Rosser, Lucy R. Wedderburn","doi":"10.1038/s41584-025-01295-w","DOIUrl":"10.1038/s41584-025-01295-w","url":null,"abstract":"The future of rheumatology research will be defined by the growing era of personalized and stratified medicine, with a focus on establishing drug-free remission. In the face of substantial global upheaval, now is the time to ensure no patient group is left behind by prioritizing research equity and inclusion.","PeriodicalId":18810,"journal":{"name":"Nature Reviews Rheumatology","volume":"21 11","pages":"644-645"},"PeriodicalIF":32.7,"publicationDate":"2025-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144840026","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-08-12DOI: 10.1038/s41584-025-01280-3
Vicky Batchelor, Thomas A. Perry, M. Zameel Cader, Tonia L. Vincent
Pain is the primary complaint in individuals with osteoarthritis (OA) and changes as the disease progresses. Anatomical changes in several joint structures potentially contribute to pain, including the increased innervation of the periosteum, synovium and subchondral bone, and the pathological innervation of articular cartilage, which is aneural under physiological conditions. Research has focused on molecules that sensitize afferent neurons, such as neuropeptides, neurotrophins, pro-inflammatory cytokines and ion channels. The neurotrophin nerve growth factor (NGF) is the best validated target in OA pain, with proven analgesic effects in preclinical and clinical studies, although the development of NGF-targeted therapeutics has been hampered by serious side effects. One relatively neglected area of research is the contribution to OA pain of the molecular pathways that mediate remodelling of nerves in disease. Remodelling requires coordination between the nerve and the associated vasculature, along with signals that are received from the surrounding parenchyma. Key cell guidance molecules, including angiogenic factors, ephrins, semaphorins and SLIT proteins are involved in nerve growth during development, and their expression is increased in osteoarthritic joints. Peripheral mechanisms of pain in osteoarthritis include nociceptor sensitization via the function of ion channels and pro-inflammatory molecules, and, potentially, pathways supporting neuronal growth and differentiation within the diseased joint. This Review discusses how neuronal trophism and neurovascular remodelling could be targeted in combination with neuronal de-sensitization or joint re-structuring approaches to reduce osteoarthritic pain.
{"title":"Peripheral neuronal sensitization and neurovascular remodelling in osteoarthritis pain","authors":"Vicky Batchelor, Thomas A. Perry, M. Zameel Cader, Tonia L. Vincent","doi":"10.1038/s41584-025-01280-3","DOIUrl":"10.1038/s41584-025-01280-3","url":null,"abstract":"Pain is the primary complaint in individuals with osteoarthritis (OA) and changes as the disease progresses. Anatomical changes in several joint structures potentially contribute to pain, including the increased innervation of the periosteum, synovium and subchondral bone, and the pathological innervation of articular cartilage, which is aneural under physiological conditions. Research has focused on molecules that sensitize afferent neurons, such as neuropeptides, neurotrophins, pro-inflammatory cytokines and ion channels. The neurotrophin nerve growth factor (NGF) is the best validated target in OA pain, with proven analgesic effects in preclinical and clinical studies, although the development of NGF-targeted therapeutics has been hampered by serious side effects. One relatively neglected area of research is the contribution to OA pain of the molecular pathways that mediate remodelling of nerves in disease. Remodelling requires coordination between the nerve and the associated vasculature, along with signals that are received from the surrounding parenchyma. Key cell guidance molecules, including angiogenic factors, ephrins, semaphorins and SLIT proteins are involved in nerve growth during development, and their expression is increased in osteoarthritic joints. Peripheral mechanisms of pain in osteoarthritis include nociceptor sensitization via the function of ion channels and pro-inflammatory molecules, and, potentially, pathways supporting neuronal growth and differentiation within the diseased joint. This Review discusses how neuronal trophism and neurovascular remodelling could be targeted in combination with neuronal de-sensitization or joint re-structuring approaches to reduce osteoarthritic pain.","PeriodicalId":18810,"journal":{"name":"Nature Reviews Rheumatology","volume":"21 9","pages":"526-545"},"PeriodicalIF":32.7,"publicationDate":"2025-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144819225","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-08-11DOI: 10.1038/s41584-025-01287-w
Nicholas Fuggle, René Rizzoli, Charlotte Beaudart, Bernard Cortet, Elizabeth M. Curtis, Mickaël Hiligsmann, Jean-Marc Kaufman, Nicola Veronese, Ben Hur Albergaria, Nasser Al-Daghri, Majed Alokail, Maria Luisa Brandi, Olivier Bruyère, Nansa Burlet, Claudia Campusano, Enrique Casado, Etienne Cavalier, Manju Chandran, Cyrus Cooper, Patrizia D’Amelio, Bess Dawson-Hughes, Peter R. Ebeling, John A. Kanis, Andreas Kurth, Radmila Matijevic, Eugene McCloskey, Michael McClung, Ouafa Mkinsi, Ngozi Njeze, Régis P. Radermecker, François Rannou, Stuart Silverman, Şansın Tüzün, Leith Zakraoui, Jean-Yves Reginster, Nicholas C. Harvey
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. This Review summarizes clinical effectiveness, health economics and safety data on the parathyroid hormone receptor agonists teriparatide and abaloparatide, discussing potential strategies and drug combinations to achieve best outcomes in patients with osteoporosis.
{"title":"Parathyroid hormone receptor agonists in the management of osteoporosis","authors":"Nicholas Fuggle, René Rizzoli, Charlotte Beaudart, Bernard Cortet, Elizabeth M. Curtis, Mickaël Hiligsmann, Jean-Marc Kaufman, Nicola Veronese, Ben Hur Albergaria, Nasser Al-Daghri, Majed Alokail, Maria Luisa Brandi, Olivier Bruyère, Nansa Burlet, Claudia Campusano, Enrique Casado, Etienne Cavalier, Manju Chandran, Cyrus Cooper, Patrizia D’Amelio, Bess Dawson-Hughes, Peter R. Ebeling, John A. Kanis, Andreas Kurth, Radmila Matijevic, Eugene McCloskey, Michael McClung, Ouafa Mkinsi, Ngozi Njeze, Régis P. Radermecker, François Rannou, Stuart Silverman, Şansın Tüzün, Leith Zakraoui, Jean-Yves Reginster, Nicholas C. Harvey","doi":"10.1038/s41584-025-01287-w","DOIUrl":"10.1038/s41584-025-01287-w","url":null,"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. This Review summarizes clinical effectiveness, health economics and safety data on the parathyroid hormone receptor agonists teriparatide and abaloparatide, discussing potential strategies and drug combinations to achieve best outcomes in patients with osteoporosis.","PeriodicalId":18810,"journal":{"name":"Nature Reviews Rheumatology","volume":"21 10","pages":"599-611"},"PeriodicalIF":32.7,"publicationDate":"2025-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144819226","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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