Rheumatoid arthritis and subsequent fracture risk: an individual person meta-analysis to update FRAX

John A Kanis¹, Helena Johansson^{2

3}, Eugene V McCloskey^{2

4}, Enwu Liu⁵, Marian Schini⁶, Liesbeth Vandenput⁷, Kristina E Åkesson^{8

9}, Fred A Anderson¹⁰, Rafael Azagra^{11

12

13

14}, Cecilie L Bager¹⁵, Charlotte Beaudart^{16

17}, Heike A Bischoff-Ferrari^{18

19}, Emmanuel Biver²⁰, Olivier Bruyère²¹, Jane A Cauley²², Jacqueline R Center^{23

24}, Roland Chapurlat²⁵, Claus Christiansen¹⁵, Cyrus Cooper^{26

27

28}, Carolyn J Crandall²⁹, Steven R Cummings³⁰, José A P da Silva^{31

32}, Bess Dawson-Hughes³³, Adolfo Diez-Perez³⁴, Alyssa B Dufour^{35

36}, John A Eisman^{23

24

37}, Petra J M Elders³⁸, Serge Ferrari²⁰, Yuki Fujita³⁹, Saeko Fujiwara⁴⁰, Claus-Christian Glüer⁴¹, Inbal Goldshtein^{42

43}, David Goltzman⁴⁴, Vilmundur Gudnason^{45

46}, Jill Hall⁴⁷, Didier Hans⁴⁸, Mari Hoff^{49

50}, Rosemary J Hollick⁵¹, Martijn Huisman^{52

53}, Masayuki Iki⁵⁴, Sophia Ish-Shalom⁵⁵, Graeme Jones⁵⁶, Magnus K Karlsson^{8

57}, Sundeep Khosla⁵⁸, Douglas P Kiel^{35

36}, Woon-Puay Koh^{59

60}, Fjorda Koromani^{61

62}, Mark A Kotowicz^{63

64

65}, Heikki Kröger^{66

67}, Timothy Kwok^{68

69}, Olivier Lamy^{70

71}, Arnulf Langhammer⁷², Bagher Larijani⁷³, Kurt Lippuner⁷⁴, Fiona E A McGuigan⁸, Dan Mellström^{75

76}, Thomas Merlijn³⁸, Tuan V Nguyen^{77

78

79}, Anna Nordström^{80

81

82}, Peter Nordström⁸³, Terence W O Neill^{84

85}, Barbara Obermayer-Pietsch⁸⁶, Claes Ohlsson^{3

87}, Eric S Orwoll⁸⁸, Julie A Pasco^{63

64

65

89}, Fernando Rivadeneira⁶¹, Anne-Marie Schott⁹⁰, Eric J Shiroma⁹¹, Kristin Siggeirsdottir^{45

92}, Eleanor M Simonsick⁹³, Elisabeth Sornay-Rendu⁹⁴, Reijo Sund⁶⁷, Karin Swart^{95

96}, Pawel Szulc⁹⁴, Junko Tamaki⁹⁷, David J Torgerson⁹⁸, Natasja M van Schoor^{99

100}, Tjeerd P van Staa¹⁰¹, Joan Vila¹⁰², Nicole C Wright¹⁰³, Noriko Yoshimura¹⁰⁴, M Carola Zillikens⁶¹, Marta Zwart^{13

14

105

106}, Nicholas C Harvey^{26

27}, Mattias Lorentzon^{3

107}, William D Leslie¹⁰⁸

Affiliations

¹ Centre for Metabolic Bone Diseases, University of Sheffield, Sheffield, UK. w.j.Pontefract@sheffield.ac.uk.
² Centre for Metabolic Bone Diseases, University of Sheffield, Sheffield, UK.
³ Sahlgrenska Osteoporosis Centre, Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
⁴ Versus Arthritis Centre for Integrated Research in Musculoskeletal Ageing, Mellanby Centre for Musculoskeletal Research, Division of Clinical Medicine, School of Medicine & Population Health, University of Sheffield, Sheffield, UK.
⁵ South Australian Health and Medical Research Institute (SAHMRI), Adelaide, Australia.
⁶ Division of Clinical Medicine, School of Medicine and Population Health, University of Sheffield, Sheffield, UK.
⁷ Sahlgrenska Osteoporosis Centre, University of Gothenburg, Gothenburg, Sweden.
⁸ Clinical and Molecular Osteoporosis Research Unit, Department of Clinical Sciences, Lund University, Lund, Sweden.
⁹ Department of Orthopedics, Skåne University Hospital, Malmö, Sweden.
¹⁰ GLOW Coordinating Center, Center for Outcomes Research, University of Massachusetts Medical School, Worcester, MA, USA.
¹¹ Department of Medicine, Autonomous University of Barcelona, Barcelona, Spain.
¹² Docencia Atenció Primària, Institut Català de La Salut, Metropolitana Nord, Barcelona, Spain.
¹³ GROIMAP/GROICAP (Research Groups), Unitat de Suport a La Recerca de Girona, Institut Universitari d'Investigació en Atenció Primària Jordi Gol, Girona, Spain.
¹⁴ PRECIOSA-Fundación Para La Investigación, Barberà del Vallés, Barcelona, Spain.
¹⁵ Nordic Bioscience A/S, Herlev, Denmark.
¹⁶ WHO Collaborating Centre for Public Health Aspects of Musculoskeletal Health and Aging, Division of Public Health, Epidemiology and Health Economics, University of Liège, Liège, Belgium.
¹⁷ Department of Health Services Research, University of Maastricht, Maastricht, the Netherlands.
¹⁸ Department of Aging Medicine and Aging Research, University Hospital Zurich and University of Zurich, Zurich, Switzerland.
¹⁹ Centre On Aging and Mobility, University of Zurich and City Hospital, Zurich, Switzerland.
²⁰ Division of Bone Diseases, Department of Medicine, Geneva University Hospitals and Faculty of Medicine, University of Geneva, Geneva, Switzerland.
²¹ Research Unit in Public Health, Epidemiology and Health Economics, University of Liège, Liège, Belgium.
²² Department of Epidemiology, School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA.
²³ Skeletal Diseases Program, Garvan Institute of Medical Research, Sydney, NSW, Australia.
²⁴ St Vincent's Clinical School, School of Medicine and Health, University of New South Wales Sydney, Sydney, NSW, Australia.
²⁵ INSERM UMR 1033, Hôpital Edouard Herriot, Université Claude Bernard-Lyon1, Lyon, France.
²⁶ MRC Lifecourse Epidemiology Centre, University of Southampton, Southampton, UK.
²⁷ NIHR Southampton Biomedical Research Centre, University of Southampton and University Hospitals Southampton NHS Foundation Trust, Southampton, UK.
²⁸ NIHR Oxford Biomedical Research Unit, University of Oxford, Oxford, UK.
²⁹ Division of General Internal Medicine and Health Services Research, David Geffen School of Medicine, University of California, Los Angeles, CA, USA.
³⁰ San Francisco Coordinating Center, California Pacific Medical Center Research Institute, San Francisco, CA, USA.
³¹ Coimbra Institute for Clinical and Biomedical Research, Faculty of Medicine, University of Coimbra, Coimbra, Portugal.
³² Rheumatology Department, Centro Hospitalar E Universitário de Coimbra, Coimbra, Portugal.
³³ Bone Metabolism Laboratory, Jean Mayer US Department of Agriculture Human Nutrition Research Center On Aging, Tufts University, Boston, MA, USA.
³⁴ Department of Internal Medicine, Hospital del Mar and CIBERFES, Autonomous University of Barcelona, Barcelona, Spain.
³⁵ Marcus Institute for Aging Research, Hebrew SeniorLife, Boston, MA, USA.
³⁶ Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
³⁷ School of Medicine Sydney, University of Notre Dame Australia, Sydney, NSW, Australia.
³⁸ Department of General Practice, Amsterdam UMC, Location AMC, Amsterdam Public Health Research Institute, Amsterdam, The Netherlands.
³⁹ Department of Hygiene and Public Health, Faculty of Medicine, Kansai Medical University, Osaka, Japan.
⁴⁰ Department of Pharmacy, Yasuda Women's University, Hiroshima, Japan.
⁴¹ Section Biomedical Imaging, Molecular Imaging North Competence Center, Department of Radiology and Neuroradiology, University Medical Center Schleswig-Holstein Kiel, Kiel University, Kiel, Germany.
⁴² Maccabitech Institute of Research and Innovation, Maccabi Healthcare Services, Tel Aviv, Israel.
⁴³ Department of Epidemiology and Preventive Medicine, School of Public Health, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
⁴⁴ Department of Medicine, McGill University and McGill University Health Centre, Montreal, Canada.
⁴⁵ Icelandic Heart Association, Kopavogur, Iceland.
⁴⁶ University of Iceland, Reykjavik, Iceland.
⁴⁷ MRC Centre for Reproductive Health, University of Edinburgh, Edinburgh, UK.
⁴⁸ Interdisciplinary Centre of Bone Diseases, Bone and Joint Department, Lausanne University Hospital (CHUV) & University of Lausanne, Lausanne, Switzerland.
⁴⁹ Department of Neuromedicine and Movement Science, Norwegian University of Science and Technology, Trondheim, Norway.
⁵⁰ Department of Rheumatology, St Olavs Hospital, Trondheim, Norway.
⁵¹ Aberdeen Centre for Arthritis and Musculoskeletal Health, Epidemiology Group, University of Aberdeen, Aberdeen, UK.
⁵² Department of Epidemiology and Data Science, Amsterdam Public Health Research Institute, VU University Medical Center, Amsterdam, The Netherlands.
⁵³ Department of Sociology, VU University, Amsterdam, The Netherlands.
⁵⁴ Department of Public Health, Faculty of Medicine, Kindai University, Osaka, Japan.
⁵⁵ Endocrine Clinic, Elisha Hospital, Haifa, Israel.
⁵⁶ Menzies Institute for Medical Research, University of Tasmania, Hobart, Australia.
⁵⁷ Department of Orthopaedics, Skåne University Hospital, Malmö, Sweden.
⁵⁸ Robert and Arlene Kogod Center On Aging and Division of Endocrinology, Mayo Clinic College of Medicine, Mayo Clinic, Rochester, MN, USA.
⁵⁹ Healthy Longevity Translational Research Programme, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
⁶⁰ Agency for Science Technology and Research (A*STAR), Singapore Institute for Clinical Sciences, Singapore, Singapore.
⁶¹ Department of Internal Medicine, Erasmus University Medical Center, Rotterdam, The Netherlands.
⁶² Department of Radiology and Nuclear Medicine, Erasmus University Medical Center, Rotterdam, The Netherlands.
⁶³ IMPACT (Institute for Mental and Physical Health and Clinical Translation), Deakin University, Geelong, VIC, Australia.
⁶⁴ Barwon Health, Geelong, VIC, Australia.
⁶⁵ Department of Medicine - Western Health, The University of Melbourne, St Albans, Victoria, Australia.
⁶⁶ Department of Orthopedics and Traumatology, Kuopio University Hospital, Kuopio, Finland.
⁶⁷ Kuopio Musculoskeletal Research Unit, University of Eastern Finland, Kuopio, Finland.
⁶⁸ Department of Medicine and Therapeutics, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, Hong Kong, China.
⁶⁹ Jockey Club Centre for Osteoporosis Care and Control, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, Hong Kong, China.
⁷⁰ Centre of Bone Diseases, Lausanne University Hospital, Lausanne, Switzerland.
⁷¹ Service of Internal Medicine, Lausanne University Hospital, Lausanne, Switzerland.
⁷² HUNT Research Centre, Department of Public Health and Nursing, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, Trondheim, Norway.
⁷³ Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran.
⁷⁴ Department of Osteoporosis, Bern University Hospital, University of Bern, Bern, Switzerland.
⁷⁵ Geriatric Medicine, Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
⁷⁶ Geriatric Medicine, Sahlgrenska University Hospital Mölndal, Mölndal, Sweden.
⁷⁷ School of Biomedical Engineering, University of Technology Sydney, Sydney, Australia.
⁷⁸ School of Population Health, UNSW Medicine, UNSW Sydney, Kensington, Australia.
⁷⁹ Tam Anh Hospital, Tam Anh Research Institute, Ho Chi Minh City, Vietnam.
⁸⁰ School of Sport Sciences, UiT The Arctic University of Norway, Tromsø, Norway.
⁸¹ Department of Health Sciences, Swedish Winter Sports Research Centre, Mid Sweden University, Östersund, Sweden.
⁸² Department of Medical Sciences, Uppsala University, Uppsala, Sweden.
⁸³ Department of Public Health and Caring Sciences, Uppsala University, Uppsala, Sweden.
⁸⁴ National Institute for Health Research Manchester Biomedical Research Centre, Manchester Academic Health Science Centre, Manchester University NHS Foundation Trust, Manchester, UK.
⁸⁵ Centre for Epidemiology Versus Arthritis, University of Manchester, Manchester, UK.
⁸⁶ Department of Internal Medicine, Division of Endocrinology and Diabetology, Medical University Graz, Graz, Austria.
⁸⁷ Department of Drug Treatment, Sahlgrenska University Hospital, Region Västra Götaland, Gothenburg, Sweden.
⁸⁸ Department of Medicine, Oregon Health and Science University, Portland, OR, USA.
⁸⁹ Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, Australia.
⁹⁰ Université Claude Bernard Lyon 1, U INSERM 1290 RESHAPE, Lyon, France.
⁹¹ Laboratory of Epidemiology and Population Sciences, National Institute On Aging, Baltimore, MD, USA.
⁹² Janus Rehabilitation, Reykjavik, Iceland.
⁹³ Translational Gerontology Branch, National Institute On Aging Intramural Research Program, Baltimore, MD, USA.
⁹⁴ INSERM UMR 1033, Hôpital Edouard Herriot, University of Lyon, Lyon, France.
⁹⁵ Department of General Practice, Amsterdam Public Health Research Institute, Amsterdam UMC, Location VUmc, Amsterdam, The Netherlands.
⁹⁶ PHARMO Institute for Drug Outcomes Research, Utrecht, The Netherlands.
⁹⁷ Department of Hygiene and Public Health, Faculty of Medicine, Educational Foundation of Osaka Medical and Pharmaceutical University, Osaka, Japan.
⁹⁸ York Trials Unit, Department of Health Sciences, University of York, York, UK.
⁹⁹ Department of Epidemiology and Data Science, Location Vrije Universiteit Amsterdam, Amsterdam UMC, Amsterdam, The Netherlands.
¹⁰⁰ Aging & Later Life, Amsterdam Public Health Research Institute, Amsterdam, The Netherlands.
¹⁰¹ Centre for Health Informatics, Faculty of Biology, Medicine and Health, School of Health Sciences, University of Manchester, Manchester, UK.
¹⁰² Statistics Support Unit, CIBER Epidemiology and Public Health (CIBERESP), Hospital del Mar Medical Research Institute, Barcelona, Spain.
¹⁰³ Department of Epidemiology, University of Alabama at Birmingham, Birmingham, AL, USA.
¹⁰⁴ Department of Preventive Medicine for Locomotive Organ Disorders, The University of Tokyo Hospital, Tokyo, Japan.
¹⁰⁵ Health Center Can Gibert del Plà, Catalan Institute of Health, Girona, Spain.
¹⁰⁶ Department of Medical Sciences, University of Girona, Girona, Spain.
¹⁰⁷ Region Västra Götaland, Geriatric Medicine, Sahlgrenska University Hospital, Mölndal, Sweden.
¹⁰⁸ Department of Medicine, University of Manitoba, Winnipeg, MB, Canada.

PMID: 39955689
DOI: 10.1007/s00198-025-07397-1

Meta-Analysis

Rheumatoid arthritis and subsequent fracture risk: an individual person meta-analysis to update FRAX

John A Kanis et al. Osteoporos Int. 2025 Apr.

. 2025 Apr;36(4):653-671.

doi: 10.1007/s00198-025-07397-1. Epub 2025 Feb 16.

Authors

Affiliations

¹ Centre for Metabolic Bone Diseases, University of Sheffield, Sheffield, UK. w.j.Pontefract@sheffield.ac.uk.
² Centre for Metabolic Bone Diseases, University of Sheffield, Sheffield, UK.
³ Sahlgrenska Osteoporosis Centre, Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
⁴ Versus Arthritis Centre for Integrated Research in Musculoskeletal Ageing, Mellanby Centre for Musculoskeletal Research, Division of Clinical Medicine, School of Medicine & Population Health, University of Sheffield, Sheffield, UK.
⁵ South Australian Health and Medical Research Institute (SAHMRI), Adelaide, Australia.
⁶ Division of Clinical Medicine, School of Medicine and Population Health, University of Sheffield, Sheffield, UK.
⁷ Sahlgrenska Osteoporosis Centre, University of Gothenburg, Gothenburg, Sweden.
⁸ Clinical and Molecular Osteoporosis Research Unit, Department of Clinical Sciences, Lund University, Lund, Sweden.
⁹ Department of Orthopedics, Skåne University Hospital, Malmö, Sweden.
¹⁰ GLOW Coordinating Center, Center for Outcomes Research, University of Massachusetts Medical School, Worcester, MA, USA.
¹¹ Department of Medicine, Autonomous University of Barcelona, Barcelona, Spain.
¹² Docencia Atenció Primària, Institut Català de La Salut, Metropolitana Nord, Barcelona, Spain.
¹³ GROIMAP/GROICAP (Research Groups), Unitat de Suport a La Recerca de Girona, Institut Universitari d'Investigació en Atenció Primària Jordi Gol, Girona, Spain.
¹⁴ PRECIOSA-Fundación Para La Investigación, Barberà del Vallés, Barcelona, Spain.
¹⁵ Nordic Bioscience A/S, Herlev, Denmark.
¹⁶ WHO Collaborating Centre for Public Health Aspects of Musculoskeletal Health and Aging, Division of Public Health, Epidemiology and Health Economics, University of Liège, Liège, Belgium.
¹⁷ Department of Health Services Research, University of Maastricht, Maastricht, the Netherlands.
¹⁸ Department of Aging Medicine and Aging Research, University Hospital Zurich and University of Zurich, Zurich, Switzerland.
¹⁹ Centre On Aging and Mobility, University of Zurich and City Hospital, Zurich, Switzerland.
²⁰ Division of Bone Diseases, Department of Medicine, Geneva University Hospitals and Faculty of Medicine, University of Geneva, Geneva, Switzerland.
²¹ Research Unit in Public Health, Epidemiology and Health Economics, University of Liège, Liège, Belgium.
²² Department of Epidemiology, School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA.
²³ Skeletal Diseases Program, Garvan Institute of Medical Research, Sydney, NSW, Australia.
²⁴ St Vincent's Clinical School, School of Medicine and Health, University of New South Wales Sydney, Sydney, NSW, Australia.
²⁵ INSERM UMR 1033, Hôpital Edouard Herriot, Université Claude Bernard-Lyon1, Lyon, France.
²⁶ MRC Lifecourse Epidemiology Centre, University of Southampton, Southampton, UK.
²⁷ NIHR Southampton Biomedical Research Centre, University of Southampton and University Hospitals Southampton NHS Foundation Trust, Southampton, UK.
²⁸ NIHR Oxford Biomedical Research Unit, University of Oxford, Oxford, UK.
²⁹ Division of General Internal Medicine and Health Services Research, David Geffen School of Medicine, University of California, Los Angeles, CA, USA.
³⁰ San Francisco Coordinating Center, California Pacific Medical Center Research Institute, San Francisco, CA, USA.
³¹ Coimbra Institute for Clinical and Biomedical Research, Faculty of Medicine, University of Coimbra, Coimbra, Portugal.
³² Rheumatology Department, Centro Hospitalar E Universitário de Coimbra, Coimbra, Portugal.
³³ Bone Metabolism Laboratory, Jean Mayer US Department of Agriculture Human Nutrition Research Center On Aging, Tufts University, Boston, MA, USA.
³⁴ Department of Internal Medicine, Hospital del Mar and CIBERFES, Autonomous University of Barcelona, Barcelona, Spain.
³⁵ Marcus Institute for Aging Research, Hebrew SeniorLife, Boston, MA, USA.
³⁶ Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
³⁷ School of Medicine Sydney, University of Notre Dame Australia, Sydney, NSW, Australia.
³⁸ Department of General Practice, Amsterdam UMC, Location AMC, Amsterdam Public Health Research Institute, Amsterdam, The Netherlands.
³⁹ Department of Hygiene and Public Health, Faculty of Medicine, Kansai Medical University, Osaka, Japan.
⁴⁰ Department of Pharmacy, Yasuda Women's University, Hiroshima, Japan.
⁴¹ Section Biomedical Imaging, Molecular Imaging North Competence Center, Department of Radiology and Neuroradiology, University Medical Center Schleswig-Holstein Kiel, Kiel University, Kiel, Germany.
⁴² Maccabitech Institute of Research and Innovation, Maccabi Healthcare Services, Tel Aviv, Israel.
⁴³ Department of Epidemiology and Preventive Medicine, School of Public Health, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
⁴⁴ Department of Medicine, McGill University and McGill University Health Centre, Montreal, Canada.
⁴⁵ Icelandic Heart Association, Kopavogur, Iceland.
⁴⁶ University of Iceland, Reykjavik, Iceland.
⁴⁷ MRC Centre for Reproductive Health, University of Edinburgh, Edinburgh, UK.
⁴⁸ Interdisciplinary Centre of Bone Diseases, Bone and Joint Department, Lausanne University Hospital (CHUV) & University of Lausanne, Lausanne, Switzerland.
⁴⁹ Department of Neuromedicine and Movement Science, Norwegian University of Science and Technology, Trondheim, Norway.
⁵⁰ Department of Rheumatology, St Olavs Hospital, Trondheim, Norway.
⁵¹ Aberdeen Centre for Arthritis and Musculoskeletal Health, Epidemiology Group, University of Aberdeen, Aberdeen, UK.
⁵² Department of Epidemiology and Data Science, Amsterdam Public Health Research Institute, VU University Medical Center, Amsterdam, The Netherlands.
⁵³ Department of Sociology, VU University, Amsterdam, The Netherlands.
⁵⁴ Department of Public Health, Faculty of Medicine, Kindai University, Osaka, Japan.
⁵⁵ Endocrine Clinic, Elisha Hospital, Haifa, Israel.
⁵⁶ Menzies Institute for Medical Research, University of Tasmania, Hobart, Australia.
⁵⁷ Department of Orthopaedics, Skåne University Hospital, Malmö, Sweden.
⁵⁸ Robert and Arlene Kogod Center On Aging and Division of Endocrinology, Mayo Clinic College of Medicine, Mayo Clinic, Rochester, MN, USA.
⁵⁹ Healthy Longevity Translational Research Programme, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
⁶⁰ Agency for Science Technology and Research (A*STAR), Singapore Institute for Clinical Sciences, Singapore, Singapore.
⁶¹ Department of Internal Medicine, Erasmus University Medical Center, Rotterdam, The Netherlands.
⁶² Department of Radiology and Nuclear Medicine, Erasmus University Medical Center, Rotterdam, The Netherlands.
⁶³ IMPACT (Institute for Mental and Physical Health and Clinical Translation), Deakin University, Geelong, VIC, Australia.
⁶⁴ Barwon Health, Geelong, VIC, Australia.
⁶⁵ Department of Medicine - Western Health, The University of Melbourne, St Albans, Victoria, Australia.
⁶⁶ Department of Orthopedics and Traumatology, Kuopio University Hospital, Kuopio, Finland.
⁶⁷ Kuopio Musculoskeletal Research Unit, University of Eastern Finland, Kuopio, Finland.
⁶⁸ Department of Medicine and Therapeutics, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, Hong Kong, China.
⁶⁹ Jockey Club Centre for Osteoporosis Care and Control, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, Hong Kong, China.
⁷⁰ Centre of Bone Diseases, Lausanne University Hospital, Lausanne, Switzerland.
⁷¹ Service of Internal Medicine, Lausanne University Hospital, Lausanne, Switzerland.
⁷² HUNT Research Centre, Department of Public Health and Nursing, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, Trondheim, Norway.
⁷³ Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran.
⁷⁴ Department of Osteoporosis, Bern University Hospital, University of Bern, Bern, Switzerland.
⁷⁵ Geriatric Medicine, Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
⁷⁶ Geriatric Medicine, Sahlgrenska University Hospital Mölndal, Mölndal, Sweden.
⁷⁷ School of Biomedical Engineering, University of Technology Sydney, Sydney, Australia.
⁷⁸ School of Population Health, UNSW Medicine, UNSW Sydney, Kensington, Australia.
⁷⁹ Tam Anh Hospital, Tam Anh Research Institute, Ho Chi Minh City, Vietnam.
⁸⁰ School of Sport Sciences, UiT The Arctic University of Norway, Tromsø, Norway.
⁸¹ Department of Health Sciences, Swedish Winter Sports Research Centre, Mid Sweden University, Östersund, Sweden.
⁸² Department of Medical Sciences, Uppsala University, Uppsala, Sweden.
⁸³ Department of Public Health and Caring Sciences, Uppsala University, Uppsala, Sweden.
⁸⁴ National Institute for Health Research Manchester Biomedical Research Centre, Manchester Academic Health Science Centre, Manchester University NHS Foundation Trust, Manchester, UK.
⁸⁵ Centre for Epidemiology Versus Arthritis, University of Manchester, Manchester, UK.
⁸⁶ Department of Internal Medicine, Division of Endocrinology and Diabetology, Medical University Graz, Graz, Austria.
⁸⁷ Department of Drug Treatment, Sahlgrenska University Hospital, Region Västra Götaland, Gothenburg, Sweden.
⁸⁸ Department of Medicine, Oregon Health and Science University, Portland, OR, USA.
⁸⁹ Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, Australia.
⁹⁰ Université Claude Bernard Lyon 1, U INSERM 1290 RESHAPE, Lyon, France.
⁹¹ Laboratory of Epidemiology and Population Sciences, National Institute On Aging, Baltimore, MD, USA.
⁹² Janus Rehabilitation, Reykjavik, Iceland.
⁹³ Translational Gerontology Branch, National Institute On Aging Intramural Research Program, Baltimore, MD, USA.
⁹⁴ INSERM UMR 1033, Hôpital Edouard Herriot, University of Lyon, Lyon, France.
⁹⁵ Department of General Practice, Amsterdam Public Health Research Institute, Amsterdam UMC, Location VUmc, Amsterdam, The Netherlands.
⁹⁶ PHARMO Institute for Drug Outcomes Research, Utrecht, The Netherlands.
⁹⁷ Department of Hygiene and Public Health, Faculty of Medicine, Educational Foundation of Osaka Medical and Pharmaceutical University, Osaka, Japan.
⁹⁸ York Trials Unit, Department of Health Sciences, University of York, York, UK.
⁹⁹ Department of Epidemiology and Data Science, Location Vrije Universiteit Amsterdam, Amsterdam UMC, Amsterdam, The Netherlands.
¹⁰⁰ Aging & Later Life, Amsterdam Public Health Research Institute, Amsterdam, The Netherlands.
¹⁰¹ Centre for Health Informatics, Faculty of Biology, Medicine and Health, School of Health Sciences, University of Manchester, Manchester, UK.
¹⁰² Statistics Support Unit, CIBER Epidemiology and Public Health (CIBERESP), Hospital del Mar Medical Research Institute, Barcelona, Spain.
¹⁰³ Department of Epidemiology, University of Alabama at Birmingham, Birmingham, AL, USA.
¹⁰⁴ Department of Preventive Medicine for Locomotive Organ Disorders, The University of Tokyo Hospital, Tokyo, Japan.
¹⁰⁵ Health Center Can Gibert del Plà, Catalan Institute of Health, Girona, Spain.
¹⁰⁶ Department of Medical Sciences, University of Girona, Girona, Spain.
¹⁰⁷ Region Västra Götaland, Geriatric Medicine, Sahlgrenska University Hospital, Mölndal, Sweden.
¹⁰⁸ Department of Medicine, University of Manitoba, Winnipeg, MB, Canada.

PMID: 39955689
DOI: 10.1007/s00198-025-07397-1

Abstract

The relationship between rheumatoid arthritis (RA) and fracture risk was estimated in an international meta-analysis of individual-level data from 29 prospective cohorts. RA was associated with an increased fracture risk in men and women, and these data will be used to update FRAX®.

Introduction: RA is a well-documented risk factor for subsequent fracture that is incorporated into the FRAX algorithm. The aim of this study was to evaluate, in an international meta-analysis, the association between rheumatoid arthritis and subsequent fracture risk and its relation to sex, age, duration of follow-up, and bone mineral density (BMD) with a view to updating FRAX.

Methods: The resource comprised 1,909,896 men and women, aged 20-116 years, from 29 prospective cohorts in which the prevalence of RA was 3% or less (primary analysis) and an additional 17 cohorts with a prevalence greater than 3% (supplementary analysis). The association between RA and fracture risk (any clinical fracture, osteoporotic fracture, major osteoporotic fracture (MOF), and hip fracture) was examined using an extension of the Poisson regression model in each cohort and each sex, followed by random-effects meta-analyses of the weighted beta coefficients.

Results: In the primary analysis, RA was reported in 1.3% of individuals. During 15,683,133 person-years of follow-up, 139,002 fractures occurred, of which 27,518 were hip fractures. RA was associated with an increased risk of any clinical fracture (hazard ratio [HR] 1.49, 95% confidence interval [CI] 1.35-1.65). The HRs were of similar magnitude for osteoporotic fracture and MOF but higher for hip fracture (HR = 2.23; 95% CI 1.85-2.69). For hip fracture, there was a significant interaction with age with higher HRs at younger ages. HRs did not differ between men and women and were independent of exposure to glucocorticoids and femoral neck BMD. Lower HRs were observed in the supplementary analysis cohorts, particularly in those with a high apparent prevalence of RA, possibly from conflation of RA with osteoarthritis.

Conclusions: A diagnosis of RA confers an increased risk of fracture that is largely independent of BMD, sex, and corticosteroids. RA should be retained as a risk factor in future iterations of FRAX with updated risk functions to improve fracture risk prediction.

Keywords: Epidemiology; FRAX; Fracture risk; Glucocorticoids; Hip fracture; Major osteoporotic fracture; Meta-analysis; Osteoporosis; Rheumatoid arthritis; Risk factors.

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Conflict of interest statement

Declarations. Ethical approval and consent to participate: All individual cohorts with candidate risk factors available have been approved by their local ethics committees, and informed consent has been obtained from all study participants with the exception of Maccabi. Informed consent was waived in Maccabi, as only deidentified, routinely collected data was used. General ethics approval for the use of all cohorts is also given by the University of Sheffield. This study does not contain any original studies with human participants or animals performed by any of the authors. Participant data are stored in coded, de-identified form. Only summary statistics and aggregate data are published, not allowing for the identification of individual study participants. Conflict of interest: JA Kanis led the team that developed FRAX as director of the WHO Collaborating Centre for Metabolic Bone Diseases; he is a director of Osteoporosis Research Ltd., which maintains FRAX. EV McCloskey, WD Leslie, M. Lorentzon, NC Harvey, M. Schini, E. Liu, L. Vandenput, and H. Johansson are members of the FRAX team. JA Kanis, NC Harvey, and EV McCloskey are members of the advisory body of the National Osteoporosis Guideline Group. KE Åkesson has no financial interest related to FRAX and chaired the National SALAR Group for Person-Centered Care Pathway Osteoporosis. FA Anderson led the team that developed GLOW while being the director of the Center for Outcomes Research at the University of Massachusetts Medical School; he has no financial interest in FRAX. R. Azagra has received funding for research from Instituto Carlos III of Spanish Ministry of Health, IDIAP Jordi Gol of Catalan Government, and from Scientific Societies SEMFYC and SEIOMM. CL Bager is employed at Nordic Bioscience and owns stock in Nordic Bioscience. She declares no competing interests in relation to this work. HA Bischoff-Ferrari has no financial interest in FRAX. For the DO-HEALTH trial cohort, Prof. Bischoff-Ferrari reports independent and investigator-initiated grants from the European Commission Framework 7 Research Program, from the University of Zurich, from NESTEC, from Pfizer Consumer Healthcare, from Streuli Pharma, plus non-financial support from DNP. For the study cohort extension, she reports independent and investigator-initiated grants from Pfizer and Vifor. Further, Prof. Bischoff-Ferrari reports non-financial support from Roche Diagnostics and personal fees from Wild, Sandoz, Pfizer, Vifor, Mylan, Roche, and Meda Pharma, outside the submitted work with regard to speaker fees and travel fees. JR Center has received honoraria for speaking at educational meetings and for advisory boards from Amgen and honoraria for an advisory board from Bayer, all unrelated to this work. R. Chapurlat has no financial interest in FRAX. He has received grant funding from Amgen, UCB, Chugai, MSD, Mylan, and Medac. He has received honoraria from Amgen, UCB, Chugai, Galapagos, Biocon, AbbVie, Haoma Medica, Pfizer, Amolyt, MSD, Lilly, BMS, Novartis, Arrow, PKMed, Kyowa-Kirin, and Sanofi. C. Christiansen owns stock in Nordic Bioscience. He declares no competing interests in relation to this work. C. Cooper reports personal fees from Alliance for Better Bone Health, Amgen, Eli Lilly, GSK, Medtronic, Merck, Novartis, Pfizer, Roche, Servier, Takeda, and UCB. JAP da Silva has no financial interest in FRAX and reports personal fees from Amgen and Fresenius-Kabi, all outside the submitted work. A. Diez-Perez reports personal fees from Theramex and owns shares of Active Life Scientific, all outside the submitted work. JA Eisman declares consulting and research support from Actavis, Amgen, Aspen, Lilly, Merck Sharp and Dohme, Novartis, Sanofi-Aventis, Servier, and Theramex. PJM Elders has no financial interest in FRAX. PJM Elders reports support for the SOS study by Stichting Achmea Gezondheidszorg, Achmea, and VGZ zorgverzekeraar. Additional support was given by the Stichting Artsenlaboratorium en Trombosedienst. Outside the submitted work, she did receive independent investigator-driven grants from ZonMw, the Netherlands; de Hartstichting, the Netherlands; the European Foundation for the Study of Diabetes, Amgen, the Netherlands; TEVA, the Netherlands; and Takeda, the Netherlands. CC Glüer reports honoraria and research support from AgNovos, Amgen, Osteolabs, and UCB unrelated to this work. NC Harvey has received consultancy/lecture fees/honoraria/grant funding from Alliance for Better Bone Health, Amgen, MSD, Eli Lilly, Radius Health, Servier, Shire, UCB, Kyowa Kirin, Consilient Healthcare, Theramex, and Internis Pharma. DP Kiel has no financial interest in FRAX but has received support for his work in the Framingham Study over the past 32 years from the National Institutes of Health, AstraZeneca, Merck, Amgen, and Radius Health. MA Kotowicz has received funding from the National Health and Medical Research Council (NHMRC) Australia, the Medical Research Future Fund (MRFF) Australia, and Amgen. He has served on advisory boards for Amgen Australia, Novartis, and Eli Lilly—all unrelated to this work—and is the Director of the Geelong Bone Densitometry Service. M. Lorentzon has received lecture fees from Amgen, Lilly, Meda, Renapharma, and UCB Pharma, and consulting fees from Amgen, Radius Health, UCB Pharma, Renapharma, Parexel International, and Consilient Health, all outside the presented work. EV McCloskey has received consultancy/lecture fees/grant funding/honoraria from AgNovos, Amgen, AstraZeneca, Consilient Healthcare, Fresenius Kabi, Gilead, GSK, Hologic, Internis, Lilly, Merck, Novartis, ObsEva, Pfizer, Radius Health, Redx Oncology, Roche, Sanofi Aventis, UCB, ViiV, Warner Chilcott, and I3 Innovus. C. Ohlsson is listed as a coinventor on two patent applications regarding probiotics in osteoporosis treatment. TW O’Neill reports honoraria from UCB unrelated to this work. ES Orwoll reports consulting fees from Angios, Biocon, Radius, and Bayer. JA Pasco has received funding from the National Health and Medical Research Council (NHMRC) Australia, the Medical Research Future Fund (MRFF), Australia, and Amgen, all unrelated to this work. M. Schini received funding for her fellowship from the Medical Research Council Centre of Excellence for Musculoskeletal Ageing, from the Osteoporosis 2000 support group, and from Roche Diagnostics, and honoraria from MA Health care and Kyowa Kirin—all unrelated to this work. KMA Swart is an employee of the PHARMO Institute for Drug Outcomes Research. This independent research institute performs financially supported studies for the government, related healthcare authorities, and several pharmaceutical companies. NC Wright sits on the Board of Trustees of the US Bone Health and Osteoporosis Foundation and has received consulting fees from Radius and ArgenX. M. Zwart has received research funding from national societies (SEMFYC and SEIOMM). C. Beaudart, E. Biver, O. Bruyère, JA Cauley, CJ Crandall, SR Cummings, B. Dawson-Huges, AB Dufour, S. Ferrari, Y. Fujita, S. Fujiwara, I. Goldshtein, D. Goltzman, V. Gudnason, J. Hall, D. Hans, M. Hoff, RJ Hollick, M. Huisman, M. Iki, S. Ish-Shalom, H. Johansson, G. Jones, MK Karlsson, S. Khosla, W–P Koh, F. Koromani, H. Kröger, T. Kwok, O. Lamy, A. Langhammer, B. Larijani, WD Leslie, K. Lippuner, E. Liu, FEA Mcguigan, D. Mellström, T. Merlijn, T. Nguyen, A. Nordström, P. Nordström, B. Obermayer-Pietsch, F. Rivadeneira, A-M Schott, EJ Shiroma, K. Sigeirsdottir, EM Simonsick, E. Sornay-Rendu, R. Sund, P. Szulc, J. Tamaki, DJ Torgerson, L. Vandenput, NM van Schoor, TP van Staa, J. Vila, N. Yoshimura, and MC Zillikens declare no competing interests in relation to this work.

References

1. van Staa TP, Geusens P, Bijlsma JW, Leufkens HG, Cooper C (2006) Clinical assessment of the longterm risk of fracture in patients with rheumatoid arthritis. Arthritis Rheum 54:3104–3112 - DOI - PubMed
1. Adami G, Gatti D, Rossini M, Giollo A, Gatti M, Bertoldo F, Bertoldo E, Mudano AS, Saag KG, Viapiana O, Fassio A (2004) Risk of fracture in women with glucocorticoid requiring diseases is independent from glucocorticoid use: an analysis on a nation-wide database. Bone 179:116958. https://doi.org/10.1016/j.bone.2023.116958 - DOI
1. Lin YC, Li YH, Chang CH, Hu CC, Chen DW, Hsieh PH, Lee MS, Ueng SW, Chang Y (2015) Rheumatoid arthritis patients with hip fracture: a nationwide study. Osteoporos Int 26:811–817. https://doi.org/10.1007/s00198-014-2968-y - DOI - PubMed
1. Jin S, Hsieh E, Peng L, Yu C, Wang Y, Wu C, Wang Q, Li M, Zeng X (2018) Incidence of fractures among patients with rheumatoid arthritis: a systematic review and meta-analysis. Osteoporos Int 29:1263–1275 - DOI - PubMed
1. Xue AL, Wu SY, Jiang L, Feng AM, Guo HF, Zhao P (2017) Bone fracture risk in patients with rheumatoid arthritis: a meta-analysis. Medicine (Baltimore) 96(36):e6983. https://doi.org/10.1097/MD.0000000000006983 - DOI - PubMed

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Rheumatoid arthritis and subsequent fracture risk: an individual person meta-analysis to update FRAX

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Rheumatoid arthritis and subsequent fracture risk: an individual person meta-analysis to update FRAX

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