ASSOCIAÇÃO ENTRE FRATURAS ATÍPICAS DO FÉMUR E O USO DE BIFOSFONATOS – REVISÃO DA LITERATURA | THE ASSOCIATION BETWEEN ATYPICAL FEMORAL FRACTURES AND BIPHOSPHONATES – REVIEW OF THE LITERATURE

Miguel Pádua Figueiredo, Marco Pato, Catarina Pereira, Fernando Amaral, Paulo Felicíssimo

Resumo


RESUMO
Introdução: Os bifosfonatos são a principal classe farmacológica usada na terapia anti-reabsortiva para a Osteoporose.
Apesar da sua eficácia comprovada, vários trabalhos recentes sugeriram uma associação entre estes fármacos e o aparecimento
de fraturas atípicas do fémur (FA). Materiais e Métodos: Os autores efetuaram uma revisão da literatura relativa a esta temá-
tica na língua inglesa e portuguesa. Foram revistos 426 resumos e selecionados 94 artigos para revisão final. Resultados: A
mudança dos critérios na definição e a qualidade dos estudos realizados são os principais limitadores na compreensão desta
associação. Apesar de haver uma associação aparente entre estes fármacos e as FA, a intensidade desta é menos clara. Por
outro lado os bifosfonatos têm décadas de experiência clínica, com vários ensaios clínicos e metanálises a demonstrar a sua
eficácia a prevenir uma proporção muito mais significativa de fraturas osteoporóticas. Conclusões: Os bifosfonatos continuam
a ser a escolha de primeira linha no tratamento da Osteoporose. São necessários mais estudos por forma a estabelecer com
clareza a relação entre os bifosfonatos e FA e que elucidem como controlar e prevenir este fenómeno.

Palavras-chave: Fracturas Atípicas do fémur; Bifosfonatos

 

ABSTRACT
Introduction: Biphosphonates are the main class of drugs used in the treatment of Osteoporosis. Despite having their efficacy proven,
several papers point to an association between these drugs and atypical femoral fractures. Materials and Methods: The authors reviewed
the Portuguese and English literature related to this subject. A total of 426 abstracts were initially reviewed and 94 papers were selected for
final analysis. Results: The change of the defining criteria and the quality of the present studies are the main limitation in comprehending
this association. Although there is a clear association between these drugs and atypical femoral fractures, its magnitude is less clear. On the
other hand, bisphosphonates rely on decades of clinical experience, with several clinical trials and meta-analysis showing their efficacy in
preventing a much more significant proportion of osteoporotic fractures. Conclusions: Bisphosphonates should still be the first-line choice
regarding the treatment of Osteoporosis. More studies are needed in order to establish a clear relation between biphosphonates and atypical
femoral fractures and to help us prevent this phenomenon.

Keywords: Atypical Femoral fractures; Biphosphonates


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Referências


Bilezikian JP Efficacy of bisphosphonates in reducing fracture risk in postmenopausal osteoporosis. Am J Med. 2009 Feb;122(2 Suppl):S14-21.

doi: 10.1016/j.amjmed.2008.12.003.

McClung M, Harris ST, Miller PD, Bauer DC, Davison KS, Dian L, et al. Bisphosphonate therapy for osteoporosis: benefits, risks, and drug

holiday. Am J Med. 2013 Jan;126(1):13-20. doi: 10.1016/j.amjmed.2012.06.023.

Cummings SR, Black DM, Thompson DE, Applegate WB, Barrett-Connor E, Musliner TA, et al. Effect of alendronate on risk of fracture in women

with low bone density but without vertebral fractures: results from the Fracture Intervention Trial. JAMA. 1998 Dec 23-30;280(24):2077-82.

Bissonnette L, April PM, Dumais R, Boire G, Roux S. Atypical fracture of the tibial diaphysis associated with bisphosphonate therapy: a case

report. Bone. 2013 Oct;56(2):406-9. doi: 10.1016/j.bone.2013.07.012.

Hayashi K 1 , Aono M, Shintani K, Kazuki K. Bisphosphonate-related atypical femoral fracture with bone metastasis of breast cancer: case report and review. Anticancer Res. 2014 Mar;34(3):1245-9.

Somford MP, Draijer FW, Thomassen BJ, Chavassieux PM, Boivin G, Papapoulos SE. Bilateral fractures of the femur diaphysis in a patient

with rheumatoid arthritis on long-term treatment with alendronate: clues to the mechanism of increased bone fragility. J Bone Miner Res. 2009

Oct;24(10):1736-40. doi: 10.1359/jbmr.090408.

Edwards MH, McCrae FC, Young-Min SA. Alendronate-related femoral diaphysis fracture--what should be done to predict and prevent

subsequent fracture of the contralateral side? Osteoporos Int. 2010 Apr;21(4):701-3. doi: 10.1007/s00198-009-0986-y.

Iwamoto J, Sato Y, Uzawa M, Takeda T, Matsumoto H. Seven years’ experience with alendronate in postmenopausal Japanese women with

osteoporosis. Ther Clin Risk Manag. 2010 Apr 26;6:201-6.

Bamrungsong T, Pongchaiyakul C. Bilateral atypical femoral fractures after long-term alendronate therapy: a case report. J Med Assoc Thai. 2010

May;93(5):620-4.

Flores Santos F, Pinheiro da Silva J, Felicíssimo P. Atypical femoral fractures associated with long-term treatment with bisphosphonates. Acta

Med Port. 2013 Nov-Dec;26(6):746-50.

Gopal GK 1 , Tam KL, Krishnan SP, Maddern IL. Bisphosphonate-associated atypical subtrochanteric femur fractures in the older patient.N Z

Med J. 2014 Feb 14;127(1389):81-5.

Villiers J 1 , Clark DW 2 , Jeswani T 3 , Webster S 1 , Hepburn AL 1 . An atraumatic femoral fracture in a patient with rheumatoid arthritis and osteoporosis treated with denosumab. Case Rep Rheumatol. 2013;2013:249872. doi: 10.1155/2013/249872.

Hagen JE 1 , Miller AN 2 , Ott SM 3 , Gardner M 4 , Morshed S 5 , Jeray K 6 , et al. Association of atypical femoral fractures with bisphosphonate use by patients with varus hip geometry. J Bone Joint Surg Am. 2014 Nov 19;96(22):1905-9. doi: 10.2106/JBJS.N.00075.

Gnudi S 1 , Ripamonti C, Gualtieri G, Malavolta N. Geometry of proximal femur in the prediction of hip fracture in osteoporotic women. Br J

Radiol. 1999 Aug;72(860):729-33.

Gnudi S 1 , Sitta E, Pignotti E. Prediction of incident hip fracture by femoral neck bone mineral density and neck-shaft angle: a 5-year longitudinal study in post-menopausal females. Br J Radiol. 2012 Aug;85(1016):e467-73. doi: 10.1259/bjr/57130600.

Taormina DP 1 , Marcano AI 2 , Karia R 3 , Egol KA 4 , Tejwani NC 5 . Symptomatic atypical femoral fractures are related to underlying hip geometry. Bone. 2014 Jun;63:1-6. doi: 10.1016/j.bone.2014.02.006.

Tang WM 1 , Chiu KY, Kwan MF, Ng TP, Yau WP. Sagittal bowing of the distal femur in Chinese patients who require total knee arthroplasty. J

Orthop Res. 2005 Jan;23(1):41-5.

Chou AC 1 , Ng AC 2 , Png MA 3 , Chua DT 4 , Ng DC 5 , Howe TS 6 , et al. Bone cross-sectional geometry is not associated with atypical femoral fractures in Asian female chronic bisphosphonate users. Bone. 2015 Oct;79:170-5. doi: 10.1016/j.bone.2015.06.003.

Nieves JW 1 , Bilezikian JP, Lane JM, Einhorn TA, Wang Y, Steinbuch M,et al. Fragility fractures of the hip and femur: incidence and patient

characteristics. Osteoporos Int. 2010 Mar;21(3):399-408. doi: 10.1007/s00198-009-0962-6.

Abrahamsen B 1 , Eiken P, Eastell R. Subtrochanteric and diaphyseal femur fractures in patients treated with alendronate: a register-based national cohort study. J Bone Miner Res. 2009 Jun;24(6):1095-102. doi: 10.1359/jbmr.081247.

Hsiao FY 1 , Huang WF, Chen YM, Wen YW, Kao YH, Chen LK, et al. Hip and subtrochanteric or diaphyseal femoral fractures in alendronate users:

a 10-year, nationwide retrospective cohort study in Taiwanese women. Clin Ther. 2011 Nov;33(11):1659-67. doi: 10.1016/j.clinthera.2011.09.006.

Kim SY 1 , Schneeweiss S, Katz JN, Levin R, Solomon DH. Oral bisphosphonates and risk of subtrochanteric or diaphyseal femur fractures in a population-based cohort. J Bone Miner Res. 2011 May;26(5):993-1001. doi: 10.1002/jbmr.288.

Vestergaard P 1 , Schwartz F, Rejnmark L, Mosekilde L.Risk of femoral shaft and subtrochanteric fractures among users of bisphosphonates and

raloxifene. Osteoporos Int. 2011 Mar;22(3):993-1001. doi: 10.1007/s00198-010-1512-y.

Park-Wyllie LY 1 , Mamdani MM, Juurlink DN, Hawker GA, Gunraj N, Austin PC, et al. Bisphosphonate use and the risk of subtrochanteric or

femoral shaft fractures in older women. JAMA. 2011 Feb 23;305(8):783-9. doi: 10.1001/jama.2011.190.

Lenart BA 1 , Neviaser AS, Lyman S, Chang CC, Edobor-Osula F, Steele B et al. Association of low-energy femoral fractures with prolonged

bisphosphonate use: a case control study. Osteoporos Int. 2009 Aug;20(8):1353-62. doi: 10.1007/s00198-008-0805-x.

Girgis CM, Sher D, Seibel MJ. Atypical femoral fractures and bisphosphonate use. N Engl J Med. 2010 May 13;362(19):1848-9. doi: 10.1056/NEJMc0910389.

Thompson RN 1 , Phillips JR, McCauley SH, Elliott JR, Moran CG. Atypical femoral fractures and bisphosphonate treatment: experience in two large United Kingdom teaching hospitals. J Bone Joint Surg Br. 2012 Mar;94(3):385-90. doi: 10.1302/0301-620X.94B3.27999.

Dell RM 1 , Adams AL, Greene DF, Funahashi TT, Silverman SL, Eisemon EO, et al. Incidence of atypical nontraumatic diaphyseal fractures of the femur. J Bone Miner Res. 2012 Dec;27(12):2544-50. doi: 10.1002/jbmr.1719.

Meier RP 1 , Perneger TV, Stern R, Rizzoli R, Peter RE. Increasing occurrence of atypical femoral fractures associated with bisphosphonate use. Arch Intern Med. 2012 Jun 25;172(12):930-6. doi: 10.1001/archinternmed.2012.1796.

Warren C 1 , Gilchrist N, Coates M, Frampton C, Helmore J, McKie J, et al. Atypical subtrochanteric fractures, bisphosphonates, blinded radiological

review. ANZ J Surg. 2012 Dec;82(12):908-12. doi: 10.1111/j.1445-2197.2012.06199.x.

Shkolnikova J 1 , Flynn J, Choong P. Burden of bisphosphonate-associated femoral fractures. ANZ J Surg. 2013 Mar;83(3):175-81. doi: 10.1111/ans.12018.

Beaudouin-Bazire C 1 , Dalmas N, Bourgeois J, Babinet A, Anract P, Chantelot C, et al. Real frequency of ordinary and atypical sub-trochanteric and diaphyseal fractures in France based on X-rays and medical file analysis. Joint Bone Spine. 2013 Mar;80(2):201-5. doi: 10.1016/j.jbspin.2012.07.012.

Schilcher J 1 , Michaëlsson K, Aspenberg P. Bisphosphonate use and atypical fractures of the femoral shaft. N Engl J Med. 2011 May 5;364(18):1728-

doi: 10.1056/NEJMoa1010650.

Feldstein AC 1 , Black D, Perrin N, Rosales AG, Friess D, Boardman D, et al. Incidence and demography of femur fractures with and without

atypical features. J Bone Miner Res. 2012 May;27(5):977-86. doi: 10.1002/jbmr.1550.

Bottai V 1 , Giannotti S, Dell’osso G, De Paola G, Menconi A, Falossi F, et al. Atypical femoral fractures: retrospective radiological study of 319

femoral fractures and presentation of clinical cases. Osteoporos Int. 2014 Mar;25(3):993-7. doi: 10.1007/s00198-013-2546-8.

Schilcher J 1 , Koeppen V, Ranstam J, Skripitz R, Michaëlsson K, Aspenberg P. Atypical femoral fractures are a separate entity, characterized by

highly specific radiographic features. A comparison of 59 cases and 218 controls. Bone. 2013 Jan;52(1):389-92. doi: 10.1016/j.bone.2012.10.016.

Gedmintas L 1 , Solomon DH, Kim SC. Bisphosphonates and risk of subtrochanteric, femoral shaft, and atypical femur fracture: a systematic

review and meta-analysis. J Bone Miner Res. 2013 Aug;28(8):1729-37. doi: 10.1002/jbmr.1893.

Liu L, Li C, Yang P, Zhu J, Gan D, Bu L, et al. Association between alendronate and atypical femur fractures: a meta-analysis. Endocr Connect. 2015

Mar;4(1):58-64. doi: 10.1530/EC-14-0120.

Black DM 1 , Schwartz AV, Ensrud KE, Cauley JA, Levis S, Quandt SA, et al. Effects of continuing or stopping alendronate after 5 years of treatment: the Fracture Intervention Trial Long-term Extension (FLEX): a randomized trial. JAMA. 2006 Dec 27;296(24):2927-38.

Mellström DD 1 , Sörensen OH, Goemaere S, Roux C, Johnson TD, Chines AA. Seven years of treatment with risedronate in women with

postmenopausal osteoporosis. Calcif Tissue Int. 2004 Dec;75(6):462-8.

Sorensen OH 1 , Crawford GM, Mulder H, Hosking DJ, Gennari C, Mellstrom D, et al. Long-term efficacy of risedronate: a 5-year placebo-

controlled clinical experience. Bone. 2003 Feb;32(2):120-6.

Chiha M 1 , Myers LE, Ball CA, Sinacore JM, Camacho PM. Long-term follow-up of patients on drug holiday from bisphosphonates: real-world

setting. Endocr Pract. 2013 Nov-Dec;19(6):989-94. doi: 10.4158/EP12425.OR.

Fukuda F, Kurinomaru N, Hijioka A. Weekly Teriparatide for Delayed Unions of Atypical Subtrochanteric Femur Fractures. Biol Ther. 2014

Dec;4(1-2):73-9. doi: 10.1007/s13554-014-0013-5.

Shane E 1 , Burr D, Ebeling PR, Abrahamsen B, Adler RA, Brown TD, et al. Atypical subtrochanteric and diaphyseal femoral fractures: report

of a task force of the American Society for Bone and Mineral Research. J Bone Miner Res. 2010 Nov;25(11):2267-94. doi: 10.1002/jbmr.253.

Saleh A, Hegde VV, Potty AG, Lane JM. Bisphosphonate therapy and atypical fractures. Orthop Clin North Am. 2013 Apr;44(2):137-51. doi:

1016/j.ocl.2013.01.001.

Fang C 1 , Chau JY 2 , Woo SB 2 , Lau TW 1 , Kwan K 1 , Leung F 3 . Propagation of bisphosphonate-related femoral stress fractures despite femoral nailing: a cautionary tale from 2 cases. Geriatr Orthop Surg Rehabil. 2014 Mar;5(1):14-7. doi: 10.1177/2151458514522058.

McKenna MJ 1 , van der Kamp S, Heffernan E, Hurson C. Incomplete atypical femoral fractures: assessing the diagnostic utility of DXA by

extending femur length. J Clin Densitom. 2013 Oct-Dec;16(4):579-83. doi: 10.1016/j.jocd.2013.06.004.

Kim S 1 , Yang KH, Lim H, Lee YK, Yoon HK, Oh CW, et al. Detection of prefracture hip lesions in atypical subtrochanteric fracture with dual-

energy x-ray absorptiometry images. Radiology. 2014 Feb;270(2):487-95. doi: 10.1148/radiol.13122691. Epub 2013 Oct 28.

Prater GL 1 , Jankowski LG 2 , Peace F 3 , Nunnally N 4 , Burroughs L 4 , Morgan SL 5 .The effect of extending femur scan length on BMD results on the Hologic Discovery-W scanner. J Clin Densitom. 2014 Oct-Dec;17(4):518-21. doi: 10.1016/j.jocd.2013.09.019. Epub 2013 Oct 29.

Unnanuntana A 1 , Saleh A, Mensah KA, Kleimeyer JP, Lane JM. Atypical femoral fractures: what do we know about them?: AAOS Exhibit

Selection. J Bone Joint Surg Am. 2013 Jan 16;95(2):e8 1-13. doi: 10.2106/JBJS.L.00568.

Franceschetti P 1 , Bondanelli M, Caruso G, Ambrosio MR, Lorusso V, Zatelli MC, et al Risk factors for development of atypical femoral fractures

in patients on long-term oral bisphosphonate therapy. Bone. 2013 Oct;56(2):426-31. doi: 10.1016/j.bone.2013.07.010.

Liu J 1 , Zhang HX, Lu XX, Hu JJ, Deng LF. Bisphosphonates and risk of subtrochanteric, femoral shaft, and atypical femur fracture: sensitivity

and trim and fill studies. Genet Test Mol Biomarkers. 2014 Feb;18(2):117-22. doi: 10.1089/gtmb.2013.0331.


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