Atypical Femur Fractures: Review of Epidemiology, Relationship to Bisphosphonates, Prevention, and Clinical Management

Endocrine Reviews
Dennis M BlackNicola Napoli

Abstract

Bisphosphonates (BPs) are highly effective in treating osteoporosis and reducing hip, vertebral, and other fractures by as much as 50% to 70%. However, since 2006, atypical femur fractures (AFFs) emerged as potential side effects of BPs and other treatments. These fractures have unusual radiologic features and occur with little trauma. Public concern has led to a >50% decrease in BP usage. AFFs are rare: for each AFF, >1200 fractures, including 135 hip fractures, are prevented. Case definition criteria were updated by the American Society of Bone and Mineral Research in 2014. Many epidemiologic studies have been reported, and although methodologically challenging, generally support a BP-AFF association. However, the magnitude of the association between BPs and AFFs is uncertain: estimates of relative risk for AFFs among BP users vs nonusers range from 1 to 65 with a meta-analysis estimate of 1.7. Although mechanistic studies have proposed several hypotheses explaining how BPs might decrease bone strength, AFF pathogenesis remains uncertain and cannot explain the paradox of efficacy of reduction of common fractures while increasing risk for rare fractures at one site. There are several consistent risk factors, including Asian ra...Continue Reading

References

Apr 1, 1993·Journal of Biomechanics·D B Burr, R B Martin
Jan 1, 1996·Journal of Orthopaedic Research : Official Publication of the Orthopaedic Research Society·C P PeterG A Rodan
Feb 29, 2000·Arthritis and Rheumatism·E M GravalleseS R Goldring
Apr 26, 2000·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·T MashibaD B Burr
Aug 30, 2000·The Journal of Bone and Joint Surgery. British Volume·P Tornetta, D Tiburzi
Jun 28, 2002·Osteoporosis International : a Journal Established As Result of Cooperation Between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA·D W Dempster
Feb 13, 2004·Health Technology Assessment : HTA·J R RossK Broadley
May 28, 2004·Endocrine-related Cancer·Janet E BrownRobert E Coleman
Jul 22, 2005·The Cochrane Database of Systematic Reviews·N PavlakisM Stockler
Aug 27, 2005·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Kenneth E S PooleJonathan Reeve
Nov 23, 2005·Best Practice & Research. Clinical Rheumatology·Mary L Bouxsein
May 25, 2006·British Journal of Sports Medicine·A IvkovicM Pecina
Jul 4, 2006·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·Ruth ZoehrerKlaus Klaushofer
Sep 26, 2006·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·Erich DurchschlagKlaus Klaushofer
Nov 10, 2006·The New England Journal of Medicine·Reina Armamento-VillarealDeborah Novack
Dec 28, 2006·JAMA : the Journal of the American Medical Association·Dennis M BlackUNKNOWN FLEX Research Group
Mar 16, 2007·The Journal of Bone and Joint Surgery. British Volume·S-K GohT S Howe
Aug 1, 2007·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·Matthew R Allen, David B Burr
Sep 26, 2007·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·Stuart L SilvermanUNKNOWN Consensus Panel of the ASBMR, ISCD, and NOF
Dec 21, 2007·Osteoporosis International : a Journal Established As Result of Cooperation Between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA·M R AllenP D Delmas
Mar 21, 2008·The New England Journal of Medicine·Brett A LenartJoseph M Lane
Jul 19, 2008·The New England Journal of Medicine·Ernest B K KwekTet Sen Howe
Oct 14, 2008·Osteoporosis International : a Journal Established As Result of Cooperation Between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA·S Y TangD Vashishth
Dec 31, 2008·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·Bo AbrahamsenRichard Eastell
Apr 28, 2009·Journal of Orthopaedic Research : Official Publication of the Orthopaedic Research Society·David B BurrMatthew R Allen
Jul 8, 2009·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·P RoschgerK Klaushofer
Aug 13, 2009·The New England Journal of Medicine·Steven R CummingsUNKNOWN FREEDOM Trial
Jan 27, 2010·Journal of Orthopaedic Trauma·Joyce S B KohTet Sen Howe
Feb 5, 2010·Journal of Clinical Rheumatology : Practical Reports on Rheumatic & Musculoskeletal Diseases·Michael D Breglia, John D Carter
Mar 26, 2010·The New England Journal of Medicine·Dennis M BlackUNKNOWN HORIZON Pivotal Fracture Trial Steering Committee
Apr 9, 2010·International Journal of Rheumatic Diseases·Joon Kiong Lee
May 14, 2010·The New England Journal of Medicine·Christian M GirgisMarkus J Seibel
Jul 2, 2010·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·Desmond PadhiEdward Posvar
Sep 16, 2010·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·Elizabeth ShaneUNKNOWN American Society for Bone and Mineral Research
Sep 25, 2010·Clinical Orthopaedics and Related Research·Yong-Chan HaKyung-Hoi Koo
Nov 19, 2010·Osteoporosis International : a Journal Established As Result of Cooperation Between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA·R RizzoliC Cooper
Dec 15, 2010·Bone·Roland BaronR Graham G Russell
Dec 17, 2010·Calcified Tissue International·Peter VestergaardLeif Mosekilde

❮ Previous
Next ❯

Citations

Oct 18, 2019·JAMA : the Journal of the American Medical Association·Kristine E Ensrud, Carolyn J Crandall
Oct 9, 2019·Current Opinion in Endocrinology, Diabetes, and Obesity·Vidita DivanRuban Dhaliwal
Feb 28, 2020·Current Osteoporosis Reports·Elizabeth M CurtisNicholas C Harvey
Mar 21, 2020·Journal of Orthopaedic Trauma·Robert B ConleyDouglas P Kiel
Jul 14, 2020·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Carla I Ripamonti, Nicola Napoli
Aug 20, 2020·The New England Journal of Medicine·Dennis M BlackAnnette L Adams
Sep 7, 2019·BMC Musculoskeletal Disorders·Shao-Chun WuChing-Hua Hsieh
Aug 1, 2020·Current Osteoporosis Reports·Kyle D AndersonRyan D Ross
Mar 19, 2020·Osteoporosis International : a Journal Established As Result of Cooperation Between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA·M K SkjødtD Prieto-Alhambra
Jun 9, 2020·The Journal of Nutrition, Health & Aging·J E Morley
Oct 3, 2018·The New England Journal of Medicine·Clifford J Rosen
Mar 13, 2020·Osteoporosis International : a Journal Established As Result of Cooperation Between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA·M L BianchiUNKNOWN Rare Bone Disease Action Group of the European Calcified Tissue Society
Sep 21, 2019·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·Robert B ConleyDouglas P Kiel
Oct 23, 2020·Tissue Engineering. Part B, Reviews·Zhi ZhengHua Wei
Oct 25, 2020·Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association·Pieter EvenepoelUNKNOWN European Renal Osteodystrophy (EUROD) workgroup, an initiative of the CKD-MBD working group of the ERA-EDTA, and the committ
Dec 1, 2020·The New England Journal of Medicine·Susan M Ott, Susan R Heckbert
Dec 12, 2020·Seminars in Musculoskeletal Radiology·Johan L BloemIris M Noebauer-Huhmann
Sep 10, 2019·Journal of Bone Oncology·Matthew LockwoodIssam Makhoul
Feb 3, 2021·Current Osteoporosis Reports·Douglas C Bauer, Bo Abrahamsen
Nov 2, 2020·Bone·Neil BinkleyKristyn Hare
Jan 13, 2021·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·Delphine FarlayGeorges Boivin
Dec 1, 2020·The New England Journal of Medicine·Mark Garton
Dec 5, 2020·BMC Musculoskeletal Disorders·Joan C LoMonika A Izano
Feb 16, 2021·Current Osteoporosis Reports·Wei ZhouM Carola Zillikens
Feb 17, 2021·European Journal of Orthopaedic Surgery & Traumatology : Orthopédie Traumatologie·O PearceA Riddick
Feb 3, 2021·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·Gareth CrouchChristian M Girgis
Dec 1, 2020·The New England Journal of Medicine·Dennis M BlackAnnette L Adams
Mar 23, 2021·Aging Clinical and Experimental Research·Osvaldo D MessinaWilliam Lems
Apr 18, 2021·Journal of Endocrinological Investigation·A FalchettiN Napoli
Apr 25, 2021·Osteoporosis International : a Journal Established As Result of Cooperation Between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA·J-T KimC H Park
Mar 17, 2021·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·Socrates PapapoulosArthur Santora
May 13, 2021·Climacteric : the Journal of the International Menopause Society·R D Langer
May 18, 2021·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·Nicola Napoli
May 24, 2021·Endocrinology and Metabolism Clinics of North America·Robert A Adler

❮ Previous
Next ❯

Related Concepts

Related Feeds

Birth Defects

Birth defects encompass structural and functional alterations that occur during embryonic or fetal development and are present since birth. The cause may be genetic, environmental or unknown and can result in physical and/or mental impairment. Here is the latest research on birth defects.

Related Papers

Journal of Orthopaedic Trauma
Joseph BorrelliSaam Morshed
The New England Journal of Medicine
Dennis M Black, Clifford Rosen
Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research
Elizabeth ShaneMichael Whyte
© 2022 Meta ULC. All rights reserved