Advertisement

The Role of Lower-Limb Geometry in the Pathophysiology of Atypical Femoral Fracture

  • Ifaz T. Haider
  • Prism S. Schneider
  • W. Brent EdwardsEmail author
Epidemiology and Pathophysiology (F Cosman and D Shoback, Section Editors)
  • 9 Downloads
Part of the following topical collections:
  1. Topical Collection on Epidemiology and Pathophysiology

Abstract

Purposeof Review

The etiology of atypical femoral fracture (AFF) is likely multifactorial. In this review, we examined the recent literature investigating the role of lower-limb geometry in the pathophysiology of AFF.

Recent Findings

Increased femoral bowing was associated with prevalent AFF and a greater likelihood of a diaphyseal versus a subtrochanteric AFF location. Femoral neck geometry or hip alignment may also be related to AFF, but findings remain equivocal. Differences in femoral geometry may, in part, be responsible for the high rate of AFF in Asian compared with Caucasian populations. Finally, simulation studies suggest that lower-limb geometry influences AFF risk via its effects on mechanical strain of the lateral femoral cortex.

Summary

Femoral geometry, and bowing in particular, is related to prevalent AFF, but more prospective investigation is needed to determine whether measurements of geometry can be used for clinical risk stratification.

Keywords

Osteoporosis Bisphophonates Femoral bowing Hip geometry Femoral strain Fracture risk 

Notes

Compliance with Ethical Standards

Conflict of Interest

Ifaz Haider and Brent Edwards reports grants from Amgen outside the submitted work. Prism Schneider declares no conflict of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. 1.
    Shane E, Burr D, Abrahamsen B, Adler RA, Brown TD, Cheung AM, et al. 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. 2014;29:1–23.CrossRefGoogle Scholar
  2. 2.
    Lo JC, Huang SY, Lee GA, Khandewal S, Provus J, Ettinger B, et al. Clinical correlates of atypical femoral fracture. Bone. 2012;51:181–4.CrossRefGoogle Scholar
  3. 3.
    Shane E, Burr D, Abrahamsen B, Adler RA, Brown TD, Cheung AM, 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;25:2267–94.CrossRefGoogle Scholar
  4. 4.
    Kwek EBK, Goh SK, Koh JSB, Png MA. Howe T Sen. An emerging pattern of subtrochanteric stress fractures: a long-term complication of alendronate therapy? Injury. 2008;39:224–31.CrossRefGoogle Scholar
  5. 5.
    Neviaser AS, Lane JM, Lenart BA, Edobor-Osula F, Lorich DG. Low-energy femoral shaft fractures associated with alendronate use. J Orthop Trauma. 2008;22:346–50.CrossRefGoogle Scholar
  6. 6.
    Goh S-K, Yang KY, Koh JSB, Wong MK, Chua SY, Chua DTC. Subtrochanteric insufficiency fractures in patients on alendronate therapy. J Bone Joint Surg (Br). 2007;89:349–53.CrossRefGoogle Scholar
  7. 7.
    Shane E, 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;25:2267–94.CrossRefGoogle Scholar
  8. 8.
    Feldstein AC, Black D, Perrin N, Rosales AG, Friess D, Boardman D, et al. Incidence and demography of femoral fractures with and without atypical features. J Bone Miner Res. 2012;27:977–86.CrossRefGoogle Scholar
  9. 9.
    • Mahjoub Z, Jean S, Leclerc JT, Brown JP, Boulet D, Pelet S, et al. Incidence and characteristics of atypical femoral fractures: clinical and geometrical data. J Bone Miner Res. 2016;31:767–76 This study examined femoral neck geometry in AFF patients compared with controls who experienced a traumatic or fragility fracture. AFF patients had more varus femoral neck-shaft angle, greater femoral neck offset, and smaller femoral head and neck diameter. CrossRefGoogle Scholar
  10. 10.
    Schilcher J, Michaelsson K, Aspenberg P. Bisphosphonate use and atypical fractures of the femoral shaft. N Engl J Med. 2011;364:1728–37.CrossRefGoogle Scholar
  11. 11.
    Brauer CA, Coca-Perraillon M, Cutler DM, Rosen AB. Incidence and mortality of hip fractures in the United States. J Am Med Assoc. 2009;302:1573–9.CrossRefGoogle Scholar
  12. 12.
    Adams AL, Shi J, Takayanagi M, Dell RM. Ten-year hip fracture incidence rate trends in a large California population, 1997–2006. Osteoporosis Int. 2013;24:373–376.Google Scholar
  13. 13.
    Schilcher J, Koeppen V, Aspenberg P, Michaëlsson K. Risk of atypical femoral fracture during and after bisphosphonate use. Acta Orthop. 2015;86:100–7.CrossRefGoogle Scholar
  14. 14.
    •• Lim S-J, Yeo I, Yoon P-W, Yoo JJ, Rhyu K-H, Han S-B, et al. Incidence, risk factors, and fracture healing of atypical femoral fractures: a multicenter case-control study. Osteoporos Int. 2018; One of the largest studies to explore AFF and femoral geometry, comparing 196 women with AFF against 94 women with TFF. AFF was associated with greater lateral and anterior bowing compared with controls, but no differences in femoral neck-shaft angle were reported.;29:2427–35.CrossRefGoogle Scholar
  15. 15.
    Ettinger B, Burr DB, Ritchie RO. Proposed pathogenesis for atypical femoral fractures: lessons from materials research. Bone. 2013;55:495–500.CrossRefGoogle Scholar
  16. 16.
    Odvina CV, Zerwekh JE, Rao DS, Maalouf N, Gottschalk FA, Pak CYC. Severely suppressed bone turnover : a potential complication of alendronate therapy. J Clin Endocrinol Metab. 2005;90:1294–301.CrossRefGoogle Scholar
  17. 17.
    Allen MR, Gineyts E, Leeming DJ. Bisphosphonates alter trabecular bone collagen cross-linking and isomerization in beagle dog vertebra. Osteoporos Int. 2008;19:329–37.CrossRefGoogle Scholar
  18. 18.
    Acevedo C, Bale H, Gludovatz B, Wat A, Tang SY, Wang M, et al. Alendronate treatment alters bone tissues at multiple structural levels in healthy canine cortical bone. Bone. 2015;81:352–63.CrossRefGoogle Scholar
  19. 19.
    Gourion-arsiquaud S, Allen MR, Burr DB, Vashishth D, Tang SY, Boskey AL. Bisphosphonate treatment modifies canine bone mineral and matrix properties and their heterogeneity. Bone. 2010;46:666–72.CrossRefGoogle Scholar
  20. 20.
    Donnelly E, Meredith DS, Nguyen JT, Gladnick BP, Rebolledo BJ, Shaffer AD, et al. Reduced cortical bone compositional heterogeneity with bisphosphonate treatment in postmenopausal women with intertrochanteric and subtrochanteric fractures. J Bone Miner Res. 2015;27:672–8.CrossRefGoogle Scholar
  21. 21.
    Allen MR, Iwata K, Phipps R, Burr DB. Alterations in canine vertebral bone turnover , microdamage accumulation , and biomechanical properties following 1-year treatment with clinical treatment doses of risedronate or alendronate. Bone. 2006;39:872–9.CrossRefGoogle Scholar
  22. 22.
    Yamagami Y, Mashiba T, Iwata K, Tanaka M, Nozaki K, Yamamoto T. Effects of minodronic acid and alendronate on bone remodeling, microdamage accumulation, degree of mineralization and bone mechanical properties in ovariectomized cynomolgus monkeys. Bone. 2013;54:1–7.CrossRefGoogle Scholar
  23. 23.
    Allen MR, Reinwald S, Burr DB. Alendronate reduces bone toughness of ribs without significantly increasing microdamage accumulation in dogs following 3 years of daily treatment. Calcif Tissue Int. 2008;82:354–60.CrossRefGoogle Scholar
  24. 24.
    Burr DB, Liu Z, Allen MR. Duration-dependent effects of clinically relevant oral alendronate doses on cortical bone toughness in beagle dogs. Bone. 2015;71:58–62.CrossRefGoogle Scholar
  25. 25.
    Hagen JE, Miller AN, Ott SM, Gardner M, Morshed S, Jeray K, et al. Association of atypical femoral fractures varus hip geometry. J Bone Jt Surg. 2014;96:1905–9.CrossRefGoogle Scholar
  26. 26.
    Chou ACC, Ng ACM, Png MA, Chua DTC, Ng DCE, Howe TS, et al. Bone cross-sectional geometry is not associated with atypical femoral fractures in Asian female chronic bisphosphonate users. Bone. 2015;79:170–5.CrossRefGoogle Scholar
  27. 27.
    Saita Y, Ishijima M, Mogami A, Kubota M, Baba T, Kaketa T, et al. The fracture sites of atypical femoral fractures are associated with the weight-bearing lower limb alignment. Bone. 2014;66:105–10.CrossRefGoogle Scholar
  28. 28.
    Hyodo K, Nishino T, Kamada H, Nozawa D, Mishima H, Yamazaki M. Location of fractures and the characteristics of patients with atypical femoral fractures: analyses of 38 Japanese cases. J Bone Miner Metab. 2017;35:209–14.CrossRefGoogle Scholar
  29. 29.
    Yoo H, Cho Y, Park Y, Ha S. Lateral femoral bowing and the location of atypical femoral fractures. Hip Pelvis. 2017;29:127–32.CrossRefGoogle Scholar
  30. 30.
    •• Kim JW, Kim JJ, Byun YS, Shon OJ, Oh HK, Park KC, et al. Factors affecting fracture location in atypical femoral fractures: a cross-sectional study with 147 patients. Injury. 2017;48:1570–4 One of the largest studies to look at factors influencing AFF fracture location. A total of 147 patients with AFF were separated into diaphyseal and subtrochanteric fracture groups. Age, BMD, and lateral and anterior bowing angles were significantly related to AFF fracture location, with greater bowing associated with more diaphyseal fractures. CrossRefGoogle Scholar
  31. 31.
    Chen LP, Chang TK, Huang TY, Kwok TG, Lu YC. The correlation between lateral bowing angle of the femur and the location of atypical femur fractures. Calcif Tissue Int. 2014;95:240–7.CrossRefGoogle Scholar
  32. 32.
    Soh HH, Chua ITH, Kwek EBK. Atypical fractures of the femur: effect of anterolateral bowing of the femur on fracture location. Arch Orthop Trauma Surg. 2015;135:1485–90.CrossRefGoogle Scholar
  33. 33.
    Haider IT, Schneider P, Michalski A, Edwards WB. Influence of geometry on proximal femoral shaft strains: implications for atypical femoral fracture. Bone. 2018;110:295–303.CrossRefGoogle Scholar
  34. 34.
    Buitendijk SKC, van de Laarschot DM, Smits AAA, Koromani F, Rivadeneira F, Beck TJ, et al. Trabecular bone score and hip structural analysis in patients with atypical femur fractures. J Clin Densitom. 2018;In Press:1–9.Google Scholar
  35. 35.
    Oh Y, Wakabayashi Y, Kurosa Y, Fujita K, Okawa A. Potential pathogenic mechanism for stress fractures of the bowed femoral shaft in the elderly: mechanical analysis by the CT-based finite element method. Injury. 2014;45:1764–71.CrossRefGoogle Scholar
  36. 36.
    •• Oh Y, Fujita K, Wakabayashi Y, Kurosa Y, Okawa A. Location of atypical femoral fracture can be determined by tensile stress distribution influenced by femoral bowing and neck-shaft angle: a CT-based nonlinear finite element analysis model for the assessment of femoral shaft loading stress. Injury. 2017;48:2736–43 This is a simulation study looking at femoral strains, and to our knowledge, the only study to compare strain predictions from AFF patients against controls. Comparing 12 patients with midshaft AFF, 10 with subtrochanteric AFF, and 10 individuals with thigh pain but not radiographic evidence of fracture, the study found that AFF site corresponded to location of peak strain, and that bowing angle was related to magnitude of peak strain. A Kruskal-Wallis test revealed statically significant differences in peak strain amongst the 3 groups, but more detailed post-hoc comparisons were not reported. CrossRefGoogle Scholar
  37. 37.
    Sasaki S, Miyakoshi N, Hongo M, Kasukawa Y, Shimada Y. Low-energy diaphyseal femoral fractures associated with bisphosphonate use and severe curved femur: a case series. J Bone Miner Metab. 2012;30:561–7.CrossRefGoogle Scholar
  38. 38.
    •• Jang SP, Yeo I, So SY, Kim K, Moon YW, Park YS, et al. Atypical femoral shaft fractures in female bisphosphonate users were associated with an increased anterolateral femoral bow and a thicker lateral cortex: a case-control study. Biomed Res Int. 2017;2017. A recent study reporting that both lateral and anterior bowing angles were greater in AFF patients vs. controls with typical osteoporotic fracture.:1–10.CrossRefGoogle Scholar
  39. 39.
    Oh Y, Wakabayashi Y, Kurosa Y, Ishizuki M, Okawa A. Stress fracture of the bowed femoral shaft is another cause of atypical femoral fracture in elderly Japanese: a case series. J Orthop Sci. 2014;19:579–86.CrossRefGoogle Scholar
  40. 40.
    • Morin SN, Wall M, Belzile EL, Godbout B, Moser TP, Michou L, et al. Assessment of femur geometrical parameters using EOS (TM) imaging technology in patients with atypical femur fractures; preliminary results. Bone. 2016;83:184–9 In this well-controlled study, 16 women with AFF were compared against age-, sex-, height-, and BP exposure–matched controls. Patients with AFF had greater lateral bowing angles compared with controls. Femoral bowing was also more prominent in patients with a midshaft fracture vs. a subtrochanteric fracture. Differences in femoral neck geometry or lower extremity alignment were not significant. CrossRefGoogle Scholar
  41. 41.
    Taormina DP, Marcano AI, Karia R, Egol KA, Tejwani NC. Symptomatic atypical femoral fractures are related to underlying hip geometry. Bone. 2014;63:1–6.CrossRefGoogle Scholar
  42. 42.
    • Haider IT, Schneider P, Michalski A, Edwards WB. Influence of geometry on proximal femoral shaft strains: Implications for atypical femoral fracture. Bone. 2018;110. A simulation study used parametric mesh morphing to quantify the relationship between femoral geometry and strain. These simulations confirm a direct causal link between femoral geometry and strain, with shaft diameter and bowing angles reported having the greatest effect on peak strain. Increased bowing angle caused a distal shift in the location of peak strain, consistent with clinical observations that elevated femoral curvature is related to more distal AFF locations.:295–303.CrossRefGoogle Scholar
  43. 43.
    Petersen TL, Engh GA. Radiographic assessment of knee alignment after total knee arthroplasty. J Arthroplast. 1988;3:67–72.CrossRefGoogle Scholar
  44. 44.
    Matsumoto T, Hashimura M, Takayama K, Ishida K, Kawakami Y, Matsuzaki T, et al. A radiographic analysis of alignment of the lower extremities - initiation and progression of varus-type knee osteoarthritis. Osteoarthr Cartil. 2015;23:217–23.CrossRefGoogle Scholar
  45. 45.
    Oka H, Muraki S, Akune T, Nakamura K, Kawaguchi H, Yoshimura N. Normal and threshold values of radiographic parameters for knee osteoarthritis using a computer-assisted measuring system (KOACAD): the ROAD study. J Orthop Sci. 2010;15:781–9.CrossRefGoogle Scholar
  46. 46.
    Koeppen VA, Schilcher J, Aspenberg P. Dichotomous location of 160 atypical femoral fractures. Acta Orthop. 2013;84:561–4.CrossRefGoogle Scholar
  47. 47.
    Schilcher J, Howe TS, Png MA, Aspenberg P, Koh JSB. Atypical fractures are mainly subtrochanteric in Singapore and Diaphyseal in Sweden: a cross-sectional study. J Bone Miner Res. 2015;30:2127–32.CrossRefGoogle Scholar
  48. 48.
    • Lo JC, Hui RL, Grimsrud CD, Chandra M, Neugebauer RS, Gonzalez JR, et al. The association of race/ethnicity and risk of atypical femur fracture among older women receiving oral bisphosphonate therapy. Bone. 2016;85:142–7 This was a retrospective epidemiological survey from a large integrated healthcare delivery system in northern California, looking at 48 000 BP users. Controlling for age and BP exposure, Asian women were 6.6 times more likely to experience AFF compared with Caucasian women. CrossRefGoogle Scholar
  49. 49.
    Dell RM, 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;27:2544–50.CrossRefGoogle Scholar
  50. 50.
    U.S. Census Bureau. Modified Race Data 2010 [Internet]. Available from: https://www.census.gov/data/datasets/2010/demo/popest/modified-race-data-2010.html. Accessed 10 Mar 2019.
  51. 51.
    Marcano A, Taormina D, Egol KA, Peck V, Tejwani NC. Are race and sex associated with the occurrence of atypical femoral fractures? Clin Orthop Relat Res. 2014;472:1020–7.CrossRefGoogle Scholar
  52. 52.
    Nakamura T, Turner CH, Yoshikawa T, Slemenda CW, Peacock M, Burr DB, et al. Do variations in hip geometry explain differences in hip fracture risk between japanese and white americans? J Bone Miner Res. 1994;9:1071–6.CrossRefGoogle Scholar
  53. 53.
    Maratt J, Schilling PL, Holcombe S, Dougherty R, Murphy R, Wang SC, et al. Variation in the femoral bow: a novel high-throughput analysis of 3922 femurs on cross-sectional imaging. J Orthop Trauma. 2014;28:6–9.CrossRefGoogle Scholar
  54. 54.
    Abdelaal AHK, Yamamoto N, Hayashi K, Takeuchi A, Morsy AF, Miwa S, et al. Radiological assessment of the femoral bowing in Japanese population. Sicot-J. 2016;2:2.CrossRefGoogle Scholar
  55. 55.
    Carter DR, Caler WE, Spengler DM, Frankel VH. Fatigue behavior of adult cortical bone: the influence of mean strain and strain range. Acta Orthop. 1981;52:481–90.CrossRefGoogle Scholar
  56. 56.
    Pattin CA, Caler WE, Carter DR. Cyclic mechanical property degradation during fatigue loading of cortical bone. J Biomech. 1996;29:69–79.CrossRefGoogle Scholar
  57. 57.
    Koch JC. The laws of bone architecture. Am J Anat. 1917;21:177–298.CrossRefGoogle Scholar
  58. 58.
    Edwards WB, Gillette JC, Thomas JM, Derrick TR. Internal femoral forces and moments during running: implications for stress fracture development. Clin Biomech (Bristol, Avon). Elsevier Ltd. 2008;23:1269–78.CrossRefGoogle Scholar
  59. 59.
    Aamodt A, Lund-Larsen J, Eine J, Andersen E, Benum P, Husby OS. In vivo measurements show tensile axial strain in the proximal lateral aspect of the human femur. J Orthop Res. 1997;15:927–31.CrossRefGoogle Scholar
  60. 60.
    Martelli S, Pivonka P, Ebeling PR. Femoral shaft strains during daily activities: implications for atypical femoral fractures. Clin Biomech Elsevier Ltd. 2014;29:869–76.CrossRefGoogle Scholar
  61. 61.
    Duda GN, Heller M, Albinger J, Schulz O, Schneider E, Claes L. Influence of muscle forces on femoral strain distribution. J Biomech. 1998;31:841–6.CrossRefGoogle Scholar
  62. 62.
    Mirzaali MJ, Schwiedrzik JJ, Thaiwichai S, Best JP, Michler J, Zysset PK, et al. Mechanical properties of cortical bone and their relationships with age, gender, composition and microindentation properties in the elderly. Bone. 2016;93:196–211.CrossRefGoogle Scholar
  63. 63.
    Kumar N, Tejwani NC. Bilateral low-energy simultaneous or sequential femoral fractures in patients on long-term alendronate therapy. J Bone Jt Surg. 2009;91:2556–61.CrossRefGoogle Scholar
  64. 64.
    Schilcher J, Aspenberg P. Incidence of stress fractures of the femoral shaft in women treated with bisphosphonate. Acta Orthop. 2009;80:413–5.CrossRefGoogle Scholar
  65. 65.
    Haider IT, Goldak J, Frei H. Femoral fracture load and fracture pattern is accurately predicted using a gradient-enhanced quasi-brittle finite element model. Med Eng Phys. 2018;55:1–8.CrossRefGoogle Scholar
  66. 66.
    De Pieri E, Lunn DE, Chapman GJ, Rasmussen KP, Ferguson SJ, Redmond AC. Patient characteristics affect hip contact forces during gait. Osteoarthr Cartil. 2019;In Press.Google Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Ifaz T. Haider
    • 1
    • 2
  • Prism S. Schneider
    • 2
    • 3
  • W. Brent Edwards
    • 1
    • 2
    Email author
  1. 1.Human Performance Laboratory, Faculty of KinesiologyUniversity of CalgaryCalgaryCanada
  2. 2.McCaig Institute for Bone and Joint HealthUniversity of CalgaryCalgaryCanada
  3. 3.Department of Surgery; Department of Community Health Sciences, Cumming School of Medicine, Foothills CampusUniversity of CalgaryCalgaryCanada

Personalised recommendations