Black, D.M., Geiger, E.J., Eastell, R. orcid.org/0000-0002-0323-3366 et al. (5 more authors) (2020) Atypical Femur Fracture Risk versus Fragility Fracture Prevention with Bisphosphonates. New England Journal of Medicine, 383 (8). pp. 743-753. ISSN 0028-4793
Abstract
BACKGROUND Bisphosphonates are effective in reducing hip and osteoporotic fractures. However, concerns about atypical femur fractures have contributed to substantially decreased bisphosphonate use, and the incidence of hip fractures may be increasing. Important uncertainties remain regarding the association between atypical femur fractures and bisphosphonates and other risk factors.
METHODS We studied women 50 years of age or older who were receiving bisphosphonates and who were enrolled in the Kaiser Permanente Southern California health care system; women were followed from January 1, 2007, to November 30, 2017. The primary outcome was atypical femur fracture. Data on risk factors, including bisphosphonate use, were obtained from electronic health records. Fractures were radiographically adjudicated. Multivariable Cox models were used. The risk–benefit profile was modeled for 1 to 10 years of bisphosphonate use to compare associated atypical fractures with other fractures prevented.
RESULTS Among 196,129 women, 277 atypical femur fractures occurred. After multivariable adjustment, the risk of atypical fracture increased with longer duration of bisphosphonate use: the hazard ratio as compared with less than 3 months increased from 8.86 (95% confidence interval [CI], 2.79 to 28.20) for 3 years to less than 5 years to 43.51 (95% CI, 13.70 to 138.15) for 8 years or more. Other risk factors included race (hazard ratio for Asians vs. Whites, 4.84; 95% CI, 3.57 to 6.56), height, weight, and glucocorticoid use. Bisphosphonate discontinuation was associated with a rapid decrease in the risk of atypical fracture. Decreases in the risk of osteoporotic and hip fractures during 1 to 10 years of bisphosphonate use far outweighed the increased risk of atypical fracture among Whites but less so among Asians. After 3 years, 149 hip fractures were prevented and 2 bisphosphonate-associated atypical fractures occurred in Whites, as compared with 91 and 8, respectively, in Asians.
CONCLUSIONS The risk of atypical femur fracture increased with longer duration of bisphosphonate use and rapidly decreased after bisphosphonate discontinuation. Asians had a higher risk than Whites. The absolute risk of atypical femur fracture remained very low as compared with reductions in the risk of hip and other fractures with bisphosphonate treatment. (Funded by Kaiser Permanente and others.)
Metadata
Item Type: | Article |
---|---|
Authors/Creators: |
|
Copyright, Publisher and Additional Information: | Copyright © 2020 Massachusetts Medical Society. All rights reserved. Reproduced in accordance with the publisher's self-archiving policy. |
Keywords: | Aged; Aged, 80 and over; Asian; Bone Density Conservation Agents; Diphosphonates; Female; Femoral Fractures; Hip Fractures; Humans; Incidence; Middle Aged; Multivariate Analysis; Osteoporosis, Postmenopausal; Osteoporotic Fractures; Proportional Hazards Models; Risk Assessment; Risk Factors; Time Factors; White People |
Dates: |
|
Institution: | The University of Sheffield |
Academic Units: | The University of Sheffield > Faculty of Medicine, Dentistry and Health (Sheffield) > Department of Human Metabolism (Sheffield) The University of Sheffield > Faculty of Medicine, Dentistry and Health (Sheffield) > The Medical School (Sheffield) > Division of Genomic Medicine (Sheffield) > Department of Oncology and Metabolism (Sheffield) |
Funding Information: | Funder Grant number MEDICAL RESEARCH COUNCIL MR/P020941/1 |
Depositing User: | Symplectic Sheffield |
Date Deposited: | 06 Jan 2023 11:43 |
Last Modified: | 06 Jan 2023 11:43 |
Published Version: | http://dx.doi.org/10.1056/nejmoa1916525 |
Status: | Published |
Publisher: | Massachusetts Medical Society |
Refereed: | Yes |
Identification Number: | 10.1056/nejmoa1916525 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:194764 |