Atypical Subtrochanteric and Diaphyseal Femoral Fractures: Second Report of a Task Force of the American Society for Bone and Mineral Research

E. Shane, D. Burr, B. Abrahamsen, R. A. Adler, T.D. Brown, A.M. Cheung, F. Cosman, J.R. Curtis, R. Dell, D.W. Dempster, P.R. Ebeling, T.A. Einhorn, H.K. Genant, P. Geusens, K. Klaushofer, J.M. Lane, F. McKiernan, R. McKinney, A. Ng, J. NievesR. O'Keefe, S. Papapoulos, T.S. Howe, M.C.H. van der Meulen, R.S. Weinstein, M.P. Whyte

Research output: Contribution to journalArticleAcademicpeer-review

347 Citations (Scopus)

Abstract

Bisphosphonates (BPs) and denosumab reduce the risk of spine and nonspine fractures. Atypical femur fractures (AFFs) located in the subtrochanteric region and diaphysis of the femur have been reported in patients taking BPs and in patients on denosumab, but they also occur in patients with no exposure to these drugs. In this report, we review studies on the epidemiology, pathogenesis, and medical management of AFFs, published since 2010. This newer evidence suggests that AFFs are stress or insufficiency fractures. The original case definition was revised to highlight radiographic features that distinguish AFFs from ordinary osteoporotic femoral diaphyseal fractures and to provide guidance on the importance of their transverse orientation. The requirement that fractures be noncomminuted was relaxed to include minimal comminution. The periosteal stress reaction at the fracture site was changed from a minor to a major feature. The association with specific diseases and drug exposures was removed from the minor features, because it was considered that these associations should be sought rather than be included in the case definition. Studies with radiographic review consistently report significant associations between AFFs and BP use, although the strength of associations and magnitude of effect vary. Although the relative risk of patients with AFFs taking BPs is high, the absolute risk of AFFs in patients on BPs is low, ranging from 3.2 to 50 cases per 100,000 person-years. However, long-term use may be associated with higher risk (approximate to 100 per 100,000 person-years). BPs localize in areas that are developing stress fractures; suppression of targeted intracortical remodeling at the site of an AFF could impair the processes by which stress fractures normally heal. When BPs are stopped, risk of an AFF may decline. Lower limb geometry and Asian ethnicity may contribute to the risk of AFFs. There is inconsistent evidence that teriparatide may advance healing of AFFs. (c) 2014 American Society for Bone and Mineral Research.

Original languageEnglish
Pages (from-to)1-23
Number of pages23
JournalJournal of Bone and Mineral Research
Volume29
Issue number1
DOIs
Publication statusPublished - 1 Jan 2014

Keywords

  • BISPHOSPHONATES
  • DENOSUMAB
  • SUPPRESSION OF REMODELING
  • FRACTURES
  • STRESS FRACTURE
  • CORTICAL STRESS LESIONS
  • BISPHOSPHONATE USE
  • FEMUR FRACTURES
  • SHAFT FRACTURES
  • INTRAVENOUS BISPHOSPHONATE
  • INSUFFICIENCY FRACTURES
  • POSTMENOPAUSAL WOMEN
  • BREAST-CANCER
  • ALENDRONATE
  • PATIENT

Cite this

Shane, E. ; Burr, D. ; Abrahamsen, B. ; Adler, R. A. ; Brown, T.D. ; Cheung, A.M. ; Cosman, F. ; Curtis, J.R. ; Dell, R. ; Dempster, D.W. ; Ebeling, P.R. ; Einhorn, T.A. ; Genant, H.K. ; Geusens, P. ; Klaushofer, K. ; Lane, J.M. ; McKiernan, F. ; McKinney, R. ; Ng, A. ; Nieves, J. ; O'Keefe, R. ; Papapoulos, S. ; Howe, T.S. ; van der Meulen, M.C.H. ; Weinstein, R.S. ; Whyte, M.P. / Atypical Subtrochanteric and Diaphyseal Femoral Fractures: Second Report of a Task Force of the American Society for Bone and Mineral Research. In: Journal of Bone and Mineral Research. 2014 ; Vol. 29, No. 1. pp. 1-23.
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abstract = "Bisphosphonates (BPs) and denosumab reduce the risk of spine and nonspine fractures. Atypical femur fractures (AFFs) located in the subtrochanteric region and diaphysis of the femur have been reported in patients taking BPs and in patients on denosumab, but they also occur in patients with no exposure to these drugs. In this report, we review studies on the epidemiology, pathogenesis, and medical management of AFFs, published since 2010. This newer evidence suggests that AFFs are stress or insufficiency fractures. The original case definition was revised to highlight radiographic features that distinguish AFFs from ordinary osteoporotic femoral diaphyseal fractures and to provide guidance on the importance of their transverse orientation. The requirement that fractures be noncomminuted was relaxed to include minimal comminution. The periosteal stress reaction at the fracture site was changed from a minor to a major feature. The association with specific diseases and drug exposures was removed from the minor features, because it was considered that these associations should be sought rather than be included in the case definition. Studies with radiographic review consistently report significant associations between AFFs and BP use, although the strength of associations and magnitude of effect vary. Although the relative risk of patients with AFFs taking BPs is high, the absolute risk of AFFs in patients on BPs is low, ranging from 3.2 to 50 cases per 100,000 person-years. However, long-term use may be associated with higher risk (approximate to 100 per 100,000 person-years). BPs localize in areas that are developing stress fractures; suppression of targeted intracortical remodeling at the site of an AFF could impair the processes by which stress fractures normally heal. When BPs are stopped, risk of an AFF may decline. Lower limb geometry and Asian ethnicity may contribute to the risk of AFFs. There is inconsistent evidence that teriparatide may advance healing of AFFs. (c) 2014 American Society for Bone and Mineral Research.",
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author = "E. Shane and D. Burr and B. Abrahamsen and Adler, {R. A.} and T.D. Brown and A.M. Cheung and F. Cosman and J.R. Curtis and R. Dell and D.W. Dempster and P.R. Ebeling and T.A. Einhorn and H.K. Genant and P. Geusens and K. Klaushofer and J.M. Lane and F. McKiernan and R. McKinney and A. Ng and J. Nieves and R. O'Keefe and S. Papapoulos and T.S. Howe and {van der Meulen}, M.C.H. and R.S. Weinstein and M.P. Whyte",
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Shane, E, Burr, D, Abrahamsen, B, Adler, RA, Brown, TD, Cheung, AM, Cosman, F, Curtis, JR, Dell, R, Dempster, DW, Ebeling, PR, Einhorn, TA, Genant, HK, Geusens, P, Klaushofer, K, Lane, JM, McKiernan, F, McKinney, R, Ng, A, Nieves, J, O'Keefe, R, Papapoulos, S, Howe, TS, van der Meulen, MCH, Weinstein, RS & Whyte, MP 2014, 'Atypical Subtrochanteric and Diaphyseal Femoral Fractures: Second Report of a Task Force of the American Society for Bone and Mineral Research', Journal of Bone and Mineral Research, vol. 29, no. 1, pp. 1-23. https://doi.org/10.1002/jbmr.1998

Atypical Subtrochanteric and Diaphyseal Femoral Fractures: Second Report of a Task Force of the American Society for Bone and Mineral Research. / Shane, E.; Burr, D.; Abrahamsen, B.; Adler, R. A.; Brown, T.D.; Cheung, A.M.; Cosman, F.; Curtis, J.R.; Dell, R.; Dempster, D.W.; Ebeling, P.R.; Einhorn, T.A.; Genant, H.K.; Geusens, P.; Klaushofer, K.; Lane, J.M.; McKiernan, F.; McKinney, R.; Ng, A.; Nieves, J.; O'Keefe, R.; Papapoulos, S.; Howe, T.S.; van der Meulen, M.C.H.; Weinstein, R.S.; Whyte, M.P.

In: Journal of Bone and Mineral Research, Vol. 29, No. 1, 01.01.2014, p. 1-23.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - Atypical Subtrochanteric and Diaphyseal Femoral Fractures: Second Report of a Task Force of the American Society for Bone and Mineral Research

AU - Shane, E.

AU - Burr, D.

AU - Abrahamsen, B.

AU - Adler, R. A.

AU - Brown, T.D.

AU - Cheung, A.M.

AU - Cosman, F.

AU - Curtis, J.R.

AU - Dell, R.

AU - Dempster, D.W.

AU - Ebeling, P.R.

AU - Einhorn, T.A.

AU - Genant, H.K.

AU - Geusens, P.

AU - Klaushofer, K.

AU - Lane, J.M.

AU - McKiernan, F.

AU - McKinney, R.

AU - Ng, A.

AU - Nieves, J.

AU - O'Keefe, R.

AU - Papapoulos, S.

AU - Howe, T.S.

AU - van der Meulen, M.C.H.

AU - Weinstein, R.S.

AU - Whyte, M.P.

PY - 2014/1/1

Y1 - 2014/1/1

N2 - Bisphosphonates (BPs) and denosumab reduce the risk of spine and nonspine fractures. Atypical femur fractures (AFFs) located in the subtrochanteric region and diaphysis of the femur have been reported in patients taking BPs and in patients on denosumab, but they also occur in patients with no exposure to these drugs. In this report, we review studies on the epidemiology, pathogenesis, and medical management of AFFs, published since 2010. This newer evidence suggests that AFFs are stress or insufficiency fractures. The original case definition was revised to highlight radiographic features that distinguish AFFs from ordinary osteoporotic femoral diaphyseal fractures and to provide guidance on the importance of their transverse orientation. The requirement that fractures be noncomminuted was relaxed to include minimal comminution. The periosteal stress reaction at the fracture site was changed from a minor to a major feature. The association with specific diseases and drug exposures was removed from the minor features, because it was considered that these associations should be sought rather than be included in the case definition. Studies with radiographic review consistently report significant associations between AFFs and BP use, although the strength of associations and magnitude of effect vary. Although the relative risk of patients with AFFs taking BPs is high, the absolute risk of AFFs in patients on BPs is low, ranging from 3.2 to 50 cases per 100,000 person-years. However, long-term use may be associated with higher risk (approximate to 100 per 100,000 person-years). BPs localize in areas that are developing stress fractures; suppression of targeted intracortical remodeling at the site of an AFF could impair the processes by which stress fractures normally heal. When BPs are stopped, risk of an AFF may decline. Lower limb geometry and Asian ethnicity may contribute to the risk of AFFs. There is inconsistent evidence that teriparatide may advance healing of AFFs. (c) 2014 American Society for Bone and Mineral Research.

AB - Bisphosphonates (BPs) and denosumab reduce the risk of spine and nonspine fractures. Atypical femur fractures (AFFs) located in the subtrochanteric region and diaphysis of the femur have been reported in patients taking BPs and in patients on denosumab, but they also occur in patients with no exposure to these drugs. In this report, we review studies on the epidemiology, pathogenesis, and medical management of AFFs, published since 2010. This newer evidence suggests that AFFs are stress or insufficiency fractures. The original case definition was revised to highlight radiographic features that distinguish AFFs from ordinary osteoporotic femoral diaphyseal fractures and to provide guidance on the importance of their transverse orientation. The requirement that fractures be noncomminuted was relaxed to include minimal comminution. The periosteal stress reaction at the fracture site was changed from a minor to a major feature. The association with specific diseases and drug exposures was removed from the minor features, because it was considered that these associations should be sought rather than be included in the case definition. Studies with radiographic review consistently report significant associations between AFFs and BP use, although the strength of associations and magnitude of effect vary. Although the relative risk of patients with AFFs taking BPs is high, the absolute risk of AFFs in patients on BPs is low, ranging from 3.2 to 50 cases per 100,000 person-years. However, long-term use may be associated with higher risk (approximate to 100 per 100,000 person-years). BPs localize in areas that are developing stress fractures; suppression of targeted intracortical remodeling at the site of an AFF could impair the processes by which stress fractures normally heal. When BPs are stopped, risk of an AFF may decline. Lower limb geometry and Asian ethnicity may contribute to the risk of AFFs. There is inconsistent evidence that teriparatide may advance healing of AFFs. (c) 2014 American Society for Bone and Mineral Research.

KW - BISPHOSPHONATES

KW - DENOSUMAB

KW - SUPPRESSION OF REMODELING

KW - FRACTURES

KW - STRESS FRACTURE

KW - CORTICAL STRESS LESIONS

KW - BISPHOSPHONATE USE

KW - FEMUR FRACTURES

KW - SHAFT FRACTURES

KW - INTRAVENOUS BISPHOSPHONATE

KW - INSUFFICIENCY FRACTURES

KW - POSTMENOPAUSAL WOMEN

KW - BREAST-CANCER

KW - ALENDRONATE

KW - PATIENT

U2 - 10.1002/jbmr.1998

DO - 10.1002/jbmr.1998

M3 - Article

VL - 29

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EP - 23

JO - Journal of Bone and Mineral Research

JF - Journal of Bone and Mineral Research

SN - 0884-0431

IS - 1

ER -