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Clinical assessment of the long-term risk of fracture in patients with rheumatoid arthritis.
Open accessAbstract
Objective: To determine whether patients with rheumatoid arthritis (RA) have an increased risk of fracture, and to estimate their long‐term absolute fracture risk. Methods: We studied patients with RA ages ≥40 years in the British General Practice Research Database, each matched by age, sex, calendar time, and practice to 3 control patients. Incident fractures, as recorded in the computerized medical records, were ascertained over a median followup of 7.6 years. The fracture rate in RA patients compared with controls was adjusted for smoking, body mass index (BMI), and several clinical risk factors, and Cox proportional hazards models were used to calculate the relative risk (RR) of fracture in RA. A risk score was then developed to provide an estimate of the 5‐ and 10‐year fracture risk among RA patients. Results: There were 30,262 patients with RA, of whom 2,460 experienced a fracture during followup. Compared with controls, patients with RA had an increased risk of fracture, which was most marked at the hip (RR 2.0, 95% confidence interval [95% CI] 1.8–2.3) and spine (RR 2.4, 95% CI 2.0–2.8). Indicators of a substantially elevated risk of fracture (at the hip) included >10 years' duration of RA (RR 3.4, 95% CI 3.0–3.9), low BMI (RR 3.9, 95% CI 3.1–4.9), and use of oral glucocorticoids (RR 3.4, 95% CI 3.0–4.0). Modeling of the long‐term risk profiles revealed that, for example, in a woman age 65 years with longstanding RA whose risk factors also included low BMI, a history of fracture, and frequent use of oral glucocorticoids, the 5‐year risk of hip fracture was 5.7% (95% CI 5.3–6.1%). Conclusion: Patients with RA are at increased risk of osteoporotic fractures. This increased risk is attributable to a combination of disease activity and use of oral glucocorticoids.
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“In addition to focal bone erosions and periarticular bone loss, systemic bone loss and increased fracture risk are important components of RA (224, 239, 420 -422).”
From Receptor Activator of Nuclear Factor κB Ligand and Osteoprotegerin Regulation of Bone Remodeling in Health and Disease (2008) · cites this paper as [422]
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“This recommendation is consistent with data demonstrating that fracture risk is highest during the time of glucocorticoid exposure [104].”
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“138 142 Histomorphometric and biochemical markers analysis indicates that generalized bone loss in RA is related to a decrease in bone formation and increase in bone resorption.”
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Garbers, C., Heink, S., Korn, T., & Rose-John, S. (2018) · Nature Reviews Drug Discovery · doi:10.1038/nrd.2018.45 · Cited by 643
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The Burden of Disease in Rheumatoid Arthritis
Uhlig, T., Moe, R. H., & Kvien, T. K. (2014) · PharmacoEconomics · doi:10.1007/s40273-014-0174-6 · Cited by 209
“The increased fracture risk and risk of osteoporosis in RA is approximately twofold [69], and a similar risk of hip fracture has been reported for this patient group compared with the population without RA [70].”
ResultWu, H., Cheng, K., Guo, Q., Yang, W., Tong, L., Wang, Y., & Sun, Z. (2021) · Frontiers in Medicine · doi:10.3389/fmed.2021.787228 · Cited by 207
“He and co-workers published a study estimating the long-term absolute fracture risk of RA patients (9).”
BackgroundVosse, D., Landewé, R., van der Heijde, D. M. F. M., van der Linden, S., van Staa, T. P., & Geusens, P. (2008) · Annals of the Rheumatic Diseases · doi:10.1136/ard.2008.100503 · Cited by 196
“The observation that patients using systemic glucocorticoids and those with recent back pain had more fractures underpins the hypothesis of an increased risk of fractures in inflammatory disease, as has been shown in patients with rheumatoid arthritis.(17) While patients with AS have an increased fracture risk limited…”
ResultSelf-citationDore, R. K., Cohen, S. B., Lane, N. E., Palmer, W. E., Shergy, W. J., Zhou, L., Wang, H., Tsuji, W. H., & Newmark, R. (2009) · Annals of the Rheumatic Diseases · doi:10.1136/ard.2009.112920 · Cited by 195
“and increase the risk of fracture. Glucocorticoid use further increases fracture risk.”
BackgroundBiologic therapies and bone loss in rheumatoid arthritis
Zerbini, C., Clark, P., Méndez-Sánchez, L., Pereira, R. M., Messina, O. D., Uña, C., Adachi, J., Lems, W., Cooper, C., & Lane, N. (2017) · Osteoporosis International · doi:10.1007/s00198-016-3769-2 · Cited by 185
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Briot, K., Geusens, P., Bultink, I., Lems, W., & Roux, C. (2017) · Osteoporosis International · doi:10.1007/s00198-017-4189-7 · Cited by 182
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Roux, C. (2010) · Osteoporosis International · doi:10.1007/s00198-010-1319-x · Cited by 185
“Using the General Practice Research Database [1], 30,262 patients with RA (ages ≥40 years) were compared to controls, with a mean duration of follow-up of 4.3 years; the increased risk of clinical fracture was 1.5 (1.4–1.6), as shown in other population-based studies [4].”
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Güler-Yüksel, M., Allaart, C. F., Goekoop-Ruiterman, Y. P. M., Vries-Bouwstra, J. K. D., van Groenendael, J. H. L. M., Mallee, C., de Bois, M. H. W., Breedveld, F. C., Dijkmans, B. A. C., & Lems, W. F. (2008) · Annals of the Rheumatic Diseases · doi:10.1136/ard.2007.086348 · Cited by 164
Hauser, B., Riches, P. L., Wilson, J. F., Horne, A. E., & Ralston, S. H. (2014) · Rheumatology · doi:10.1093/rheumatology/keu162 · Cited by 163
Favalli, E. G. (2020) · Rheumatology and Therapy · doi:10.1007/s40744-020-00219-2 · Cited by 164
“…the use of glucocorticoids, commonly used in RA, is associated with reduced bone mineral density (BMD) due to a reduction in bone formation (rather than an increase in bone turn-over) [125]; however, the risk of fracture in patients with RA is increased irrespective of glucocorticoid use [126–128].”
BackgroundUsing biochemical markers of bone turnover in clinical practice
Singer, F. R., & Eyre, D. W. (2008) · Cleveland Clinic Journal of Medicine · doi:10.3949/ccjm.75.10.739 · Cited by 151
Dennison, E. M., Compston, J. E., Flahive, J., Siris, E. S., Gehlbach, S. H., Adachi, J. D., Boonen, S., Chapurlat, R. D., Díez‐Pérez, A., Anderson, F. A., et al. (2012) · Bone · doi:10.1016/j.bone.2012.02.639 · Cited by 148
“In one such study, rheumatoid arthritis was associated with an excess overall fracture risk, vertebral fracture, and hip fracture risk [9].”
BackgroundSelf-citationThe challenging interplay between rheumatoid arthritis, ageing and comorbidities
van Onna, M., & Boonen, A. E. R. C. H. (2016) · BMC Musculoskeletal Disorders · doi:10.1186/s12891-016-1038-3 · Cited by 153
“8) for a vertebral fracture [36].”
Osteoporosis Pathophysiology, Epidemiology, and Screening in Rheumatoid Arthritis
Adami, G., & Saag, K. G. (2019) · Current Rheumatology Reports · doi:10.1007/s11926-019-0836-7 · Cited by 149
Osteoimmunology and osteoporosis
Geusens, P., & Lems, W. F. (2011) · Arthritis Research & Therapy · doi:10.1186/ar3375 · Cited by 150
Self-citationBone fracture risk in patients with rheumatoid arthritis
Xue, A.-L., Wu, S.-Y., Jiang, L., Feng, A.-M., Guo, H.-F., & Zhao, P. (2017) · Medicine · doi:10.1097/md.0000000000006983 · Cited by 145
Interleukin-1 is essential for systemic inflammatory bone loss
Polzer, K., Joosten, L. A. B., Gasser, J. A., Distler, J. H. W., Ruiz, G., Baum, W., Redlich, K., Bobacz, K., Smolen, J. S., van den Berg, W., et al. (2009) · Annals of the Rheumatic Diseases · doi:10.1136/ard.2008.104786 · Cited by 143
“which showed that there is an independent role of disease activity and duration on the risk of osteoporotic fracture in many skeletal sites including the hip.”
BackgroundDietary interventions for rheumatoid arthritis
Hagen, K. B., Byfuglien, M. G., Falzon, L., Olsen, S. U., & Smedslund, G. (2009) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd006400.pub2 · Cited by 139
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Jin, S., Hsieh, E., Li, P., Yu, C., Wang, Y.-Y.-Q., Wu, C., Wang, Q., Li, K., & Zeng, X. (2018) · Osteoporosis International · doi:10.1007/s00198-018-4473-1 · Cited by 133
“Thus, three studies [29, 30, 35] were selected for the meta-analysis of all fracture risk, and 5 [8, 23, 25, 27, 33] were selected for the metaanalysis of fragility fracture risk.”
InfluentialBriot, K., Cortet, B., Roux, C., Fardet, L., Abitbol, V., Bacchetta, J., Buchon, D., Debiais, F., Guggenbuhl, P., Laroche, M., et al. (2014) · Joint Bone Spine · doi:10.1016/j.jbspin.2014.10.001 · Cited by 130
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Cutolo, M., Kitas, G. D., & van Riel, P. L. C. M. (2013) · Seminars in Arthritis and Rheumatism · doi:10.1016/j.semarthrit.2013.08.004 · Cited by 134
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“Patients with RA across all age groups and regardless of sex or anatomical sites are at an increased risk of osteoporosis and osteoporotic vertebral and non-vertebral fractures as compared to healthy patients [10,11].”
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“Rheumatoid arthritis doubles the risk of hip and vertebral fractures regardless of the use of glucocorticoids [31].”
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“6) compared with healthy controls [47].”
Ghazi, M., Kolta, S., Briot, K., Fechtenbaum, J., Paternotte, S., & Roux, C. (2011) · Osteoporosis International · doi:10.1007/s00198-011-1584-3 · Cited by 98
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InfluentialApproach to the patient with secondary osteoporosis
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BackgroundInfluentialSelf-citationMeguid, M. H. A., Hammad, Y. H., Swilam, R. S., & Barakat, M. S. (2012) · Rheumatology International · doi:10.1007/s00296-012-2375-7 · Cited by 87
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“[7] showed that patients with RA had an increased risk of fractures at both the hip (risk ratio [RR]=”
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“RA patients are known to be at increased risk of osteoporotic fractures [48-51].”
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“Rheumatoid arthritis (RA) is a chronic inflammatory disease that damages the joints and causes bone demineralization [1], thereby doubling the risk of osteoporotic fractures compared to the general population [2].”
BackgroundBiologic therapies and systemic bone loss in rheumatoid arthritis
Dimitroulas, T., Nikas, S. N., Trontzas, P., & Kitas, G. D. (2013) · Autoimmunity Reviews · doi:10.1016/j.autrev.2013.03.015 · Cited by 80
“Case control studies [18] and a meta-analysis [19] demonstrate that RA almost doubles the risk of hip and vertebral fractures, regardless of whether steroids are used or not.”
BackgroundKim, S. C., Schneeweiß, S., Liu, J. L., & Solomon, D. H. (2011) · Journal of Bone and Mineral Research · doi:10.1002/jbmr.1489 · Cited by 78
“Other sensitivity analyses were performed by including only (1) subjects with a follow-up period of 90 days or longer as a lag time period; (2) female subjects only; (3) persons with prior glucocorticoid use; (4) persons without prior glucocorticoid use; and (5) focusing only on those without a prior fracture.”
BackgroundMethodThe Role of Osteocytes in Inflammatory Bone Loss
Metzger, C. E., & Narayanan, S. A. (2019) · Frontiers in Endocrinology · doi:10.3389/fendo.2019.00285 · Cited by 82
Marder, W., Khalatbari, S. H., Myles, J. D., HENCH, R. P., Lustig, S., Yalavarthi, S., Parameswaran, A., Brook, R. D., & Kaplan, M. J. (2013) · Journal of the American Heart Association · doi:10.1161/jaha.113.000441 · Cited by 77
“RA patients, a group already at heightened risk for osteoporosis due to disease activity and corticosteroid use.(49) PPAR agonist subtypes with selectivity for PPAR-c have been associated with loss of bone density and strength in animal models and in clinical trials, due to unfavorable balance between bone formation a…”
BackgroundVis, M., Haavardsholm, E. A., Bøyesen, P., Haugeberg, G., Uhlig, T., Hoff, M., Woolf, A. D., Dijkmans, B. A. C., Lems, W. F., & Kvien, T. K. (2011) · Osteoporosis International · doi:10.1007/s00198-010-1517-6 · Cited by 76
“5 for all fractures in RA patients compared to healthy controls [4].”
BackgroundWang, Y., Zhao, R. Z., Gu, Z., Dong, C., Guo, G., & Li, L. (2020) · Osteoporosis International · doi:10.1007/s00198-020-05360-w · Cited by 75
“In the treatment of GIO, calcium and vitamin D should be supplemented with anti-osteoporosis treatment [34].”
BackgroundDental implants in patients with rheumatoid arthritis: clinical outcome and peri‐implant findings
Krennmair, G., Seemann, R., & Piehslinger, E. (2010) · Journal Of Clinical Periodontology · doi:10.1111/j.1600-051x.2010.01606.x · Cited by 74
“Patients with RA with or without concomitant corticosteroid treatment will develop localized osteopenia and generalized osteoporosis in 30–50% of all cases (Raisz 1988, van Staa et al. 2006, Nakayama 2007, Haugeberg 2008).”
Osteoclasts—Key Players in Skeletal Health and Disease
Novack, D. V., & Mbalaviele, G. (2016) · Microbiology Spectrum · doi:10.1128/microbiolspec.mchd-0011-2015 · Cited by 80
Can bone loss in rheumatoid arthritis be prevented?
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“Earlier studies have shown that patients with RA are also at an increased risk of both vertebral [47, 48] and nonvertebral fractures [49, 50].”
BackgroundBone mineral density in patients with recently diagnosed, active rheumatoid arthritis
Güler-Yüksel, M., Bijsterbosch, J., Goekoop-Ruiterman, Y. P. M., Breedveld, F. C., Allaart, C. F., Vries-Bouwstra, J. K. D., Dijkmans, B. A. C., Lems, W. F., Ronday, H. K., Peeters, A. J., et al. (2007) · Annals of the Rheumatic Diseases · doi:10.1136/ard.2007.070839 · Cited by 73
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Effects of anti-tumor necrosis factor α agents on bone
Kawai, V. K., Stein, C., Perrien, D. S., & Griffin, M. R. (2012) · Current Opinion in Rheumatology · doi:10.1097/bor.0b013e328356d212 · Cited by 70
Characteristics of fracture and related factors in patients with rheumatoid arthritis
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Pyroptosis in Osteoblasts: A Novel Hypothesis Underlying the Pathogenesis of Osteoporosis
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“include low calcium intake (3), estrogen deficiency in postmenopausal women (4, 5), autoimmune diseases, such as rheumatoid arthritis (RA) (6), and the adverse reactions of some drugs, etc.”
BackgroundClinical aspects of vitamin D in the management of rheumatoid arthritis
Leventis, P., & Patel, S. K. (2008) · Rheumatology · doi:10.1093/rheumatology/ken296 · Cited by 62
Skeletal complications of rheumatoid arthritis
Heinlen, L. D., & Humphrey, M. B. (2017) · Osteoporosis International · doi:10.1007/s00198-017-4170-5 · Cited by 64
Paskins, Z., Whittle, R., Sultan, A. A., Müller, S., Bucknall, M., Helliwell, T., Hider, S., Roddy, E., & Mallen, C. D. (2018) · BMC Medicine · doi:10.1186/s12916-017-0987-1 · Cited by 62
Effects of inflammation on bone: an update
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Common mechanisms and holistic care in atherosclerosis and osteoporosis
Szekanecz, Z., Raterman, H. G., Pethő, Z., & Lems, W. F. (2019) · Arthritis Research & Therapy · doi:10.1186/s13075-018-1805-7 · Cited by 59
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“falling,((11)) or use of glucocorticoids,((2,12)) other factors, such as a deterioration in bone microstructure and material property that are not captured by aBMD measurements can significantly compromise bone strength((13)) and contribute to the increased fracture risk associated with RA.”
BackgroundZHU, T. Y., Griffith, J. F., Qin, L., HUNG, V. W., Fong, T.-N., Au, S.-K., Tang, X., Kwok, A. W. L., Leung, P., Li, E. K., et al. (2012) · Journal of Bone and Mineral Research · doi:10.1002/jbmr.1793 · Cited by 57
“Exclusion criteria were as follows: (1) known metabolic disorder that could affect bone metabolism, such as severe renal impairment,”
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Atopic eczema and fracture risk in adults: A population-based cohort study
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RANKL as a therapeutic target of rheumatoid arthritis
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The frequency of and risk factors for osteoporosis in Korean patients with rheumatoid arthritis
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Glucocorticoid-induced osteoporosis
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Metadata
- Authors
- Staa, T. P. V., Geusens, P., Bijlsma, J. W. J., Leufkens, H. G. M., & Cooper, C.
- Affiliations
- University of Southampton (GB)
- University Medical Center Utrecht (NL)
- Utrecht University (NL)
- Venue
- Arthritis & Rheumatism
- Publisher
- Wiley
- Published
- 2006-09-28
- Volume
- 54
- Issue
- 10
- Pages
- 3104-3112
- ISSN
- 0004-3591 (ISSN-L)
- 1529-0131
- OpenAlex
- W2098986981
- Cited by
- 587
- References
- 39
- Citations by year
- 2026: 8 · 2025: 15 · 2024: 19 · 2023: 21 · 2022: 26 · 2021: 56 · 2020: 44 · 2019: 37 · 2018: 50 · 2017: 40 · 2016: 32 · 2015: 30 · 2014: 34 · 2013: 33 · 2012: 38
- FWCI
- 11.88
- Type
- journal article
- Language
- en
- Open access
- green
- dspace.library.uu.nl
- Licence
- Locations
- Arthritis & Rheumatism (publishedVersion)
- PubMed (publishedVersion)
- Research Explorer (The University of Manchester) (publishedVersion)
- Document Server@UHasselt (UHasselt) (submittedVersion)
- Utrecht University Repository (Utrecht University) (submittedVersion, other-oa)
- ePrints Soton (University of Southampton) (submittedVersion)
- Topics
- Health Sciences › Medicine › Rheumatology › Rheumatoid Arthritis Research and Therapies
- Health Sciences › Medicine › Orthopedics and Sports Medicine › Bone health and osteoporosis research
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Menopause: Health Impacts and Treatments
- Keywords
- rheumatoid arthritis, fracture risk, osteoporotic fractures, hip fracture, spinal fractures, oral corticosteroids, body mass index, disease duration
- MeSH terms
- Adult, Aged, Aged, 80 and over, Algorithms, Arthritis, Rheumatoid, Female, Glucocorticoids, Humans, Male, Middle Aged, Osteoporosis, Risk Factors, Time Factors, Cohort Studies, Case-Control Studies, Fractures, Bone
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