Do Bisphosphonates Cause Femoral Insufficiency Fractures?

Overview

Journal J Orthop Traumatol

Specialties Emergency Medicine
Orthopedics

Date 2012 Aug 2

PMID 22850908

Citations 6

Authors

Andreas Seraphim

Nawfal Al-Hadithy

Simon C Mordecai

Shafic Al-Nammari

Affiliations

Soon will be listed here.

Abstract

In recent years, several reports have suggested an association between the use of bisphosphonates and subtrochanteric insufficiency fractures. Research from animal studies and in some cases from histomorphometric data collected from patients provide evidence of a possible pathophysiological mechanism behind this phenomenon. Despite this, it has not yet been possible to confirm a causal relationship. The small number of cases, the lack of consistency in defining these atypical fractures, the absence of homogeneity between studies, and the fact that most data available are derived from retrospective observational studies, are some of the difficulties encountered in the evaluation of evidence. Despite the proven benefit of bisphosphonates at providing protection against osteoporotic fractures, caution should be used before continuing therapy for longer than 5 years.

Citing Articles

Case Report - Short-term Bisphosphonate Use Associated Stress Fractures.

Dadrewalla A, Battle J, Anakwe R J Orthop Case Rep. 2023; 12(10):78-82.

PMID: 36874892 PMC: 9983371. DOI: 10.13107/jocr.2022.v12.i10.3376.

Successful treatment for bilateral femoral neck insufficiency fractures: a rare lesion case report and an updated review of the literature.

Tan X, Lei T, Wu G, Luo H, Huang G, He C BMC Musculoskelet Disord. 2020; 21(1):102.

PMID: 32059654 PMC: 7023760. DOI: 10.1186/s12891-020-3107-x.

Simultaneous bilateral atypical femoral fracture in a patient receiving denosumab: case report and literature review.

Selga J, Nunez J, Minguell J, Lalanza M, Garrido M Osteoporos Int. 2015; 27(2):827-32.

PMID: 26501556 DOI: 10.1007/s00198-015-3355-z.

Ulnar fractures with bisphosphonate therapy: a systematic review of published case reports.

Tan S, Saseendar S, Tan B, Pawaskar A, Kumar V Osteoporos Int. 2014; 26(2):421-9.

PMID: 25227921 DOI: 10.1007/s00198-014-2885-0.

Atypical femoral fracture combined with osteonecrosis of jaw during osteoporosis treatment with bisphosphonate.

Won Y, Lim J, Kim Y, Song H, Yang K J Bone Metab. 2014; 21(2):155-9.

PMID: 25025002 PMC: 4075270. DOI: 10.11005/jbm.2014.21.2.155.

References

Pauwels F . [Importance of structural principles of the bracing and kinetic apparatus with regard to stress on the long bones]. Acta Anat (Basel). 1951; 12(1-2):207-27. View

Park-Wyllie L, Mamdani M, Juurlink D, Hawker G, Gunraj N, Austin P . Bisphosphonate use and the risk of subtrochanteric or femoral shaft fractures in older women. JAMA. 2011; 305(8):783-9. DOI: 10.1001/jama.2011.190. View

Currey J . Effects of differences in mineralization on the mechanical properties of bone. Philos Trans R Soc Lond B Biol Sci. 1984; 304(1121):509-18. DOI: 10.1098/rstb.1984.0042. View

Shane E, Burr D, Ebeling P, Abrahamsen B, Adler R, Brown T . 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(11):2267-94. DOI: 10.1002/jbmr.253. View

Kavanagh K, Guo K, Dunford J, Wu X, Knapp S, Ebetino F . The molecular mechanism of nitrogen-containing bisphosphonates as antiosteoporosis drugs. Proc Natl Acad Sci U S A. 2006; 103(20):7829-34. PMC: 1472530. DOI: 10.1073/pnas.0601643103. View

Aspenberg P, Schilcher J, Fahlgren A . Histology of an undisplaced femoral fatigue fracture in association with bisphosphonate treatment. Frozen bone with remodelling at the crack. Acta Orthop. 2010; 81(4):460-2. PMC: 2917569. DOI: 10.3109/17453674.2010.492766. View

Black D, Cummings S, Karpf D, Cauley J, Thompson D, Nevitt M . Randomised trial of effect of alendronate on risk of fracture in women with existing vertebral fractures. Fracture Intervention Trial Research Group. Lancet. 1996; 348(9041):1535-41. DOI: 10.1016/s0140-6736(96)07088-2. View

Wasserman N, Yerramshetty J, Akkus O . Microcracks colocalize within highly mineralized regions of cortical bone tissue. Eur J Morphol. 2005; 42(1-2):43-51. DOI: 10.1080/09243860500095471. View

Odvina C, Levy S, Rao S, Zerwekh J, Rao D . Unusual mid-shaft fractures during long-term bisphosphonate therapy. Clin Endocrinol (Oxf). 2009; 72(2):161-8. DOI: 10.1111/j.1365-2265.2009.03581.x. View

10.

Lenart B, Lorich D, Lane J . Atypical fractures of the femoral diaphysis in postmenopausal women taking alendronate. N Engl J Med. 2008; 358(12):1304-6. DOI: 10.1056/NEJMc0707493. View

11.

Giusti A, Hamdy N, Papapoulos S . Atypical fractures of the femur and bisphosphonate therapy: A systematic review of case/case series studies. Bone. 2010; 47(2):169-80. DOI: 10.1016/j.bone.2010.05.019. View

12.

Odvina C, Zerwekh J, Rao D, Maalouf N, Gottschalk F, Pak C . Severely suppressed bone turnover: a potential complication of alendronate therapy. J Clin Endocrinol Metab. 2004; 90(3):1294-301. DOI: 10.1210/jc.2004-0952. View

13.

Gamsjaeger S, Buchinger B, Zwettler E, Recker R, Black D, Gasser J . Bone material properties in actively bone-forming trabeculae in postmenopausal women with osteoporosis after three years of treatment with once-yearly Zoledronic acid. J Bone Miner Res. 2010; 26(1):12-8. DOI: 10.1002/jbmr.180. View

14.

Leung F, Lau T, To M, Luk K, Kung A . Atypical femoral diaphyseal and subtrochanteric fractures and their association with bisphosphonates. BMJ Case Rep. 2011; 2009. PMC: 3027310. DOI: 10.1136/bcr.10.2008.1073. View

15.

Schneider J . Should bisphosphonates be continued indefinitely? An unusual fracture in a healthy woman on long-term alendronate. Geriatrics. 2006; 61(1):31-3. View

16.

Bone H, Greenspan S, McKeever C, Bell N, Davidson M, Downs R . Alendronate and estrogen effects in postmenopausal women with low bone mineral density. Alendronate/Estrogen Study Group. J Clin Endocrinol Metab. 2000; 85(2):720-6. DOI: 10.1210/jcem.85.2.6393. View

17.

Black D, Delmas P, Eastell R, Reid I, Boonen S, Cauley J . Once-yearly zoledronic acid for treatment of postmenopausal osteoporosis. N Engl J Med. 2007; 356(18):1809-22. DOI: 10.1056/NEJMoa067312. View

18.

Abrahamsen B, Eiken P, Eastell R . Subtrochanteric and diaphyseal femur fractures in patients treated with alendronate: a register-based national cohort study. J Bone Miner Res. 2008; 24(6):1095-102. DOI: 10.1359/jbmr.081247. View

19.

Sayed-Noor A, Sjoden G . Subtrochanteric displaced insufficiency fracture after long-term alendronate therapy--a case report. Acta Orthop. 2008; 79(4):565-7. DOI: 10.1080/17453670710015580. View

20.

Chapurlat R, Arlot M, Burt-Pichat B, Chavassieux P, Roux J, Portero-Muzy N . Microcrack frequency and bone remodeling in postmenopausal osteoporotic women on long-term bisphosphonates: a bone biopsy study. J Bone Miner Res. 2007; 22(10):1502-9. DOI: 10.1359/jbmr.070609. View