Advertisement

Osteoporosis International

, Volume 30, Issue 12, pp 2417–2428 | Cite as

Natural history of incomplete atypical femoral fractures in patients after a prolonged and variable course of bisphosphonate therapy—a long-term radiological follow-up

  • M.A. PngEmail author
  • P.C. Mohan
  • J.S.B. Koh
  • C.Y. Howe
  • T.S. Howe
Original Article
  • 187 Downloads

Abstract

Summary

Understanding the natural history of lateral femoral stress fractures helps to guide their management. Improvement in their radiographic characteristics is rare. Progression was generally sequential, most developing an incomplete fracture line before fracture displacement. Stopping bisphosphonates decreased the fracture rate, a feasible management option for lesions without incomplete fracture lines.

Introduction

Retrospective study evaluating the natural history of lateral femoral stress fractures (FSF) by serial radiography over a variable period of time in a cohort of patients treated for some time with bisphosphonates for osteoporosis, whilst also identifying the fracture response in cases where bisphosphonates were discontinued.

Methods

The radiographs of 76 consecutive patients (92 femurs) with 161 FSF were reviewed to document their change over time. Femurs were classified into the following: A—normal, B—focal cortical thickening, C—dreaded black line and D—displaced fracture. Bisphosphonate history was recorded.

Results

66.5% FSF showed group stability between the first and last radiographs: group B (79.1%), group C (45.7%). 28.6% progressed, mostly following an ordered sequence starting from group A, progressing to B, then C, before culminating in D. Progression rate was as follows: A—100% (11/11), B—18.3% (21/115), C—40% (14/35). Regression in FSF was uncommon—5.6% (8/161). 34.8% (32/92) sustained displaced fractures. Kaplan-Meier analysis showed statistically significant difference between the groups; median survival (95% CI): A—4189 (-), B—3383.0 (-), C—1807 (0.0–3788.6) and progression to displaced fracture when bisphosphonate had been stopped for at least 6 months. The group without recent bisphosphonates had a lower group progression rate (17.1%, 12/70). Nevertheless, 10.9% (5/46) progressed to displaced fracture. This group also had the highest proportion of stable (77.1%, 54/70) and regressive lesions (5.7%, 4/70).

Conclusions

In FSF, there is natural progression from normal bone, to focal cortical thickening, to dreaded black line and eventually to displaced fracture. Most lesions persist, remaining static or progressing, especially if a dreaded black line is present and bisphosphonates are continued. Regression is uncommon and more frequent when bisphosphonates are discontinued. Despite stopping bisphosphonates, there remains a 10.9% risk of progression to displaced fracture.

Keywords

Atypical femoral fracture management Bisphosphonate Conservative management Insufficiency fracture Osteoporosis treatment Prophylactic surgery 

Notes

Compliance with ethical standards

The retrospective cohort study was approved by our institutional review board with waiver of informed consent.

Conflicts of interest

Meng Ai Png, P. Chandra Mohan, Choong Yin Howe and Tet Sen Howe declare that they have no conflict of interest.

Joyce S.B. Koh has received Overseas conference sponsor from Amgen Dec 2017 and Chairperson fee from Amgen Nov 2018. Amgen produces and markets Denosumab.

References

  1. 1.
    Odvina CV, Zerwekh JE, Rao DS, Maalouf N, Gottschalk FA, Pak CYC (2005) Severely suppressed bone turnover: a potential complication of alendronate therapy. J Clin Endocrinol Metab 90:1294–1301.  https://doi.org/10.1210/jc.2004-0952 CrossRefPubMedGoogle Scholar
  2. 2.
    Koh JSB, Goh SK, Png MA, Ng ACM, Howe TS (2011) Distribution of atypical fractures and cortical stress lesions in the femur: implications on pathophysiology. Singap Med J 52:77–80Google Scholar
  3. 3.
    Kwek EBK, Goh SK, Koh JSB, Png MA, Sen HT (2008) An emerging pattern of subtrochanteric stress fractures: a long-term complication of alendronate therapy? Injury 39:224–231.  https://doi.org/10.1016/j.injury.2007.08.036 CrossRefPubMedGoogle Scholar
  4. 4.
    Neviaser AS, Lane JM, Lenart BA, Edobor-Osula F, Lorich DG (2008) Low-energy femoral shaft fractures associated with alendronate use. J Orthop Trauma 22:346–350.  https://doi.org/10.1097/BOT.0b013e318172841c CrossRefPubMedGoogle Scholar
  5. 5.
    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, Sen HT, 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. J Bone Miner Res 29:1–23.  https://doi.org/10.1002/jbmr.1998 CrossRefGoogle Scholar
  6. 6.
    Isaacs JD, Shidiak L, Harris IA, Szomor ZL (2010) Femoral insufficiency fractures associated with prolonged bisphosphonate therapy. Clin Orthop Relat Res 468:3384–3392.  https://doi.org/10.1007/s11999-010-1535-x CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Edwards BJ, Bunta AD, Lane J, Odvina C, Rao DS, Raisch DW, McKoy JM, Omar I, Belknap SM, Garg V, Hahr AJ, Samaras AT, Fisher MJ, West DP, Langman CB, Stern PH (2013) Bisphosphonates and nonhealing femoral fractures: analysis of the FDA Adverse Event Reporting System (FAERS) and international safety efforts. J Bone Jt Surg-Am 95:297–307.  https://doi.org/10.2106/JBJS.K.01181 CrossRefGoogle Scholar
  8. 8.
    Koh JSB, Goh SK, Png MA, Kwek EBK, Sen HT (2010) Femoral cortical stress lesions in long-term bisphosphonate therapy: a herald of impending fracture? J Orthop Trauma 24:75–81.  https://doi.org/10.1097/BOT.0b013e3181b6499b CrossRefPubMedGoogle Scholar
  9. 9.
    Png MA, Koh JSB, Goh SK, Fook-Chong S, Sen HT (2012) Bisphosphonate-related femoral periosteal stress reactions: scoring system based on radiographic and MRI findings. Am J Roentgenol 198:869–877.  https://doi.org/10.2214/AJR.11.6794 CrossRefGoogle Scholar
  10. 10.
    Saleh A, Hegde VV, Potty AG, Schneider R, Cornell CN, Lane JM (2012) Management strategy for symptomatic bisphosphonate-associated incomplete atypical femoral fractures. HSS J 8:103–110.  https://doi.org/10.1007/s11420-012-9275-y CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Min B-W, Koo K-H, Park Y-S, Oh C-W, Lim S-J, Kim J-W, Lee K-J, Lee Y-K (2016) Novel scoring system for identifying impending complete fractures in incomplete atypical femoral fractures. J Clin Endocrinol Metab 102:jc2016–jc2787.  https://doi.org/10.1210/jc.2016-2787 CrossRefGoogle Scholar
  12. 12.
    Min A, Chan VWY, Aristizabal R, Peramaki ER, Agulnik DB, Strydom N, Ramsey D, Forster BB (2017) Clinical decision support decreases volume of imaging for low back pain in an urban emergency department. J Am Coll Radiol 14:889–899.  https://doi.org/10.1016/j.jacr.2017.03.005 CrossRefPubMedGoogle Scholar
  13. 13.
    Mohan PC, Howe TS, Koh JSB, Png MA (2013) Radiographic features of multifocal endosteal thickening of the femur in patients on long-term bisphosphonate therapy. Eur Radiol 23:222–227.  https://doi.org/10.1007/s00330-012-2587-y CrossRefPubMedGoogle Scholar
  14. 14.
    Lee Y-KK, Ha Y-CC, Kang BJ, Chang JS, Koo K-HH (2013) Predicting need for fixation of atypical femoral fracture. J Clin Endocrinol Metab 98:2742–2745.  https://doi.org/10.1210/jc.2012-4322 CrossRefPubMedGoogle Scholar
  15. 15.
    Koh A, Guerado E, Giannoudis PV (2017) Atypical femoral fractures related to bisphosphonate treatment: issues and controversies related to their surgical management. Bone Jt J 99B:295–302.  https://doi.org/10.1302/0301-620X.99B3.BJJ-2016-0276.R2 CrossRefGoogle Scholar
  16. 16.
    Egol KA, Park JH, Rosenberg ZS, Peck V, Tejwani NC (2014) Healing delayed but generally reliable after bisphosphonate-associated complete femur fractures treated with IM nails. Clin Orthop Relat Res 472:2728–2734.  https://doi.org/10.1007/s11999-013-2963-1 CrossRefPubMedGoogle Scholar
  17. 17.
    Ha YC, Cho MR, Park KH, Kim SY, Koo KH (2010) Is surgery necessary for femoral insufficiency fractures after long-term bisphosphonate therapy? Clin Orthop Relat Res 468:3393–3398.  https://doi.org/10.1007/s11999-010-1583-2 CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    Gomberg SJ, Wustrack RL, Napoli N, Arnaud CD, Black DM (2011) Teriparatide, vitamin D, and calcium healed bilateral subtrochanteric stress fractures in a postmenopausal woman with a 13-year history of continuous alendronate therapy. J Clin Endocrinol Metab 96:1627–1632.  https://doi.org/10.1210/jc.2010-2520 CrossRefPubMedGoogle Scholar
  19. 19.
    Schilcher J, Koeppen V, Aspenberg P, Michaëlsson K (2015) Risk of atypical femoral fracture during and after bisphosphonate use. Acta Orthop 86:100–107.  https://doi.org/10.3109/17453674.2015.1004149 CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    Adams AL, Adams JL, Raebel MA, Tang BT, Kuntz JL, Vijayadeva V, McGlynn EA, Gozansky WS (2018) Bisphosphonate drug holiday and fracture risk: a population-based cohort study. J Bone Miner Res 33:1252–1259.  https://doi.org/10.1002/jbmr.3420 CrossRefPubMedGoogle Scholar
  21. 21.
    Zanchetta MB, Diehl M, Buttazzoni M, Galich A, Silveira F, Bogado CE, Zanchetta JR (2014) Assessment of bone microarchitecture in postmenopausal women on long-term bisphosphonate therapy with atypical fractures of the femur. J Bone Miner Res 29:999–1004.  https://doi.org/10.1002/jbmr.2107 CrossRefPubMedGoogle Scholar
  22. 22.
    Watts NB, Diab DL (2010) Long-term use of bisphosphonates in osteoporosis. J Clin Endocrinol Metab 95:1555–1565.  https://doi.org/10.1210/jc.2009-1947 CrossRefPubMedGoogle Scholar
  23. 23.
    Watts N, Bilezikian J, Camacho P, Greenspan S, Harris S, Hodgson S, Kleerekoper M, Luckey M, McClung M, Pollack R, Petak S (2010) American Association of Clinical Endocrinologists Medical Guidelines for Clinical Practice for the diagnosis and treatment of postmenopausal osteoporosis. Endocr Pract 16:1–37.  https://doi.org/10.4158/ep.16.s3.1 CrossRefPubMedPubMedCentralGoogle Scholar
  24. 24.
    Compston JE, Bilezikian JP (2012) Bisphosphonate therapy for osteoporosis: the long and short of it. J Bone Miner Res 27:240–242.  https://doi.org/10.1002/jbmr.1494 CrossRefPubMedGoogle Scholar
  25. 25.
    Bindon B, Adams W, Balasubramanian N, Sandhu J, Camacho P (2018) Osteoporotic fractures during bisphosphonate drug holiday. Endocr Pract 24:163–169.  https://doi.org/10.4158/EP171975.OR CrossRefPubMedGoogle Scholar
  26. 26.
    Banffy MB, Vrahas MS, Ready JE, Abraham JA (2011) Nonoperative versus prophylactic treatment of bisphosphonate-associated femoral stress fractures. Clin Orthop Relat Res 469:2028–2034.  https://doi.org/10.1007/s11999-011-1828-8 CrossRefPubMedPubMedCentralGoogle Scholar
  27. 27.
    Egol KA, Park JH, Prensky C, Rosenberg ZS, Peck V, Tejwani NC (2013) Surgical treatment improves clinical and functional outcomes for patients who sustain incomplete bisphosphonate-related femur fractures. J Orthop Trauma 27:331–335CrossRefGoogle Scholar
  28. 28.
    Oh C-W, Oh J-K, Park K-C, Kim J-W, Yoon Y-C (2013) Prophylactic nailing of incomplete atypical femoral fractures. SciWorld J 2013:450148.  https://doi.org/10.1155/2013/450148 CrossRefGoogle Scholar
  29. 29.
    Weil YA, Rivkin G, Safran O, Liebergall MFA (2011) The outcome of surgically treated femur fractures associated. J Trauma 71:186–190.  https://doi.org/10.1097/TA.0b013e31821957e3 CrossRefPubMedGoogle Scholar
  30. 30.
    Teo BJX, Koh JSB, Goh SK, Png MA, Chua DTC, Howe TS (2014) Post-operative outcomes of atypical femoral subtrochanteric fracture in patients on bisphosphonate therapy. Bone Jt J 96 B:658–664CrossRefGoogle Scholar
  31. 31.
    Prasarn ML, Ahn J, Helfet DL, Lane JM, Lorich DG (2012) Bisphosphonate-associated femur fractures have high complication rates with operative fixation trauma. Clin Orthop Relat Res 470:2295–2301.  https://doi.org/10.1007/s11999-012-2412-6 CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© International Osteoporosis Foundation and National Osteoporosis Foundation 2019

Authors and Affiliations

  1. 1.Department of Diagnostic RadiologySingapore General HospitalSingaporeSingapore
  2. 2.Duke-NUS Medical SchoolSingaporeSingapore
  3. 3.Department of Orthopedic SurgerySingapore General HospitalSingaporeSingapore
  4. 4.Faculty of MathematicsUniversity of CambridgeCambridgeUK

Personalised recommendations