Bisphosphonate-associated Femur Fractures Have High Complication Rates with Operative Fixation
Purchase on Springer.com
$39.95 / €34.95 / £29.95*
Rent the article at a discountRent now
* Final gross prices may vary according to local VAT.
Bisphosphonate-associated femur fractures have been well described but the preoperative patient factors, treatment modalities, and complications of treatment are unclear.
We asked whether a diagnosis of osteoporosis, the characteristic radiographic features of bisphosphonate-related femur fractures, and complication rates differed in patients with operatively treated femoral shaft fractures receiving bisphosphonates and in patients not receiving bisphosphonates.
We retrospectively reviewed 43 patients with bisphosphonate-associated femoral shaft fractures (including subtrochanteric) from 2002 to 2008 and 20 patients with similar fractures but not treated with bisphosphonates. Similar implants were used in both groups, but a greater number of adjuvants were used in the bisphosphonate cohort. We recorded preoperative osteoporosis and radiographic findings of the characteristic bisphosphonate femur fracture and early complications. The minimum followup was 5 months (mean, 29 months; range 5–60 months).
Preoperatively a greater percentage of patients treated with bisphosphonates had confirmed osteoporosis than those not treated with bisphosphonates (24% versus 5%, respectively), a greater percentage had a proximal fracture location (48% versus 40%, respectively), and their mean cortex to shaft diameter ratio was greater (24% versus 15%, respectively). The bisphosphonate cohort had a higher rate of intraoperative fractures (21% versus 0%) and postoperative plate failures (30% versus 0%).
Despite low rates of other risk factors and ample use of biologic adjuvants, patients treated with bisphosphonates having femur fractures have more complications.
Level of Evidence
Level III, therapeutic study. See Guidelines for Authors for a complete description of levels of evidence.
- Ahn JK, Lee J, Cha HS, Koh EM. Non-traumatic fracture of the femoral shaft in a patient taking long-term bisphosphonate therapy. Rheumatol Int. 2011;31:973–975. CrossRef
- Aspenberg P. Bisphosphonate-induced fractures: nature strikes back? Acta Orthop. 2008;79:459–460. CrossRef
- Cao Y, Mori S, Mashiba T, Westmore MS, Ma L, Sato M, Akiuama T, Shi L, Komatsubara S, Miyamato K, Norimatsu H. Raloxifene, estrogen, and alendronate affect the processes of fracture repair differently in ovariectomized rats. J Bone Miner Res. 2002;17:2237–2246. CrossRef
- Capeci CM, Tejwani NC. Bilateral low-energy simultaneous or sequential femoral fractures in patients on long-term alendronate therapy. J Bone Joint Surg Am. 2009;91:2556–2561. CrossRef
- Cermak K, Shumelinsky F, Alexiou J, Gebhart MJ. Case reports: subtrochanteric femoral stress fractures after prolonged alendronate therapy. Clin Orthop Relat Res. 2010;468:1991–1996. CrossRef
- Chrischilles EA, Dasbach EJ, Rubenstein LM, Cook JR, Tabor HK, Black DM and for the Fracture Intervention Trial Research Group. The effect of alendronate on fracture-related healthcare utilization and costs: The Fracture Intervention Trial. Osteoporos Int. 2001;12:654–660. CrossRef
- Das De S, Setiobudi T, Shen L, Das De S. A rational approach to management of alendronate-related subtrochanteric fractures. J Bone Joint Surg Br. 2010;92:679–686. CrossRef
- Fisher JE, Rogers MJ, Halasy JM, Luckman SP, Hughes DE, Masarachia PJ, Wesolowski G, Russell RG, Rodan GA, Reszka AA. Alendronate mechanism of action: geranylgeraniol, an intermediate in the mevalonate pathway, prevents inhibition of osteoclast formation, bone resorption, and kinase activation in vitro. Proc Natl Acad Sci. 1999;96:133–138. CrossRef
- Goh S-K, Yang KY, Koh JS, Wong MK, Chua SY, Chua DT, Howe TS. Subtrochanteric insufficiency fractures in patients on alendronate therapy: a caution. J Bone Joint Surg Br. 2007;89:349–353. CrossRef
- Gomberg SJ, Wustrack RL, Napoli N, Arnaud CD, Black DM. 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. 2011;96:1627–1632. CrossRef
- Ha YC, Cho MR, Park KH, Kim SY, Koo KH. Is surgery necessary for femoral insufficiency fractures after long-term bisphosphonate therapy? Clin Orthop Relat Res. 2010;468:3393–3398. CrossRef
- Harris ST, Watts NB, Genant HK, McKeever CD, Hangartner T, Keller M, Chesnut CH 3rd, Brown J, Eriksen EF, Hoseyni MD, Axelrod DW, Miller PD. Effects of risedronate treatment on vertebral and nonvertebral fractures in women with postmenopausal osteoporosis: a randomized controlled trial. Vertebral Efficacy With Risedronate Therapy (VERT) Study Group. JAMA. 1999;282:1344–1352. CrossRef
- Hosking D, Chilvers CE, Christiansen C, Ravn P, Wasnich R, Ross P, McClung M, Balske A, Thompson D, Daley M, Yates AJ. Prevention of bone loss with alendronate in postmenopausal women under 60 years of age. Early Postmenopausal Intervention Cohort Study Group. N Engl J Med. 1998;338:485–492. CrossRef
- Isaacs JD, Shidiak L, Harris IA, Szomor ZL. Femoral insufficiency fractures associated with prolonged bisphosphonate therapy. Clin Orthop Relat Res. 2010;468:3384–3392. CrossRef
- Karpf DB, Shapiro DR, Seeman E, Ensrud KE, Johnston CC Jr, Adami S, Harris ST, Santora AC 2nd, Hirsch LJ, Oppenheimer L, Thompson D. Prevention of nonvertebral fractures by alendronate: a meta-analysis. Alendronate Osteoporosis Treatment Study Groups. JAMA. 1997;277:1159–1164. CrossRef
- Koh JS, Goh SK, Png MA, Kwek EB, Howe TS. Femoral cortical stress lesions in long-term bisphosphonate therapy: a herald of impending fracture? J Orthop Trauma. 2010;24:75–81. CrossRef
- Kwek EB, Goh SK, Koh JS, Png MA, Howe TS. An emerging pattern of subtrochanteric stress fractures: a long-term complication of alendronate therapy? Injury. 2008;39:224–231. CrossRef
- Lenart BA, Lorich DG, Lane JM. Atypical fractures of the femoral diaphysis in postmenopausal women taking alendronate. N Engl J Med. 2008;358:1304–1306. CrossRef
- Lenart BA, Neviaser AS, Lyman S, Chang CC, Edobor-Osula F, Steele B, van der Meulen MC, Lorich DG, Lane JM. Association of low-energy femoral fractures with prolonged bisphosphonate use: a case control study. Osteoporosis Int. 2009;20:1353–1362. CrossRef
- Liberman UA, Weiss SR, Broll J, Minne HW, Quan H, Bell NH, Rodriguez-Portales J, Downs RW Jr, Dequeker J, Favus M. Effect of oral alendronate on bone mineral density and the incidence of fractures in postmenopausal osteoporosis. The Alendronate Phase III Osteoporosis Treatment Study Group. N Engl J Med. 1995;333:1437–1443. CrossRef
- Luckman SP, Hughes DE, Coxon FP, Graham R, Russell G, Rogers MJ. Nitrogen-containing bisphosphonates inhibit the mevalonate pathway and prevent post-translational prenylation of GTP-binding proteins, including Ras. J Bone Miner Res. 1998;13:581–589. CrossRef
- Mashiba T, Hui S, Turner CH, Mori S, Johnston CC, Burr DB. Bone remodeling at the iliac crest can predict the changes in remodeling dynamics, microdamage accumulation, and mechanical properties in the lumbar vertebrae of dogs. Calcif Tissue Int. 2005;77:180–185. CrossRef
- Mashiba T, Mori S, Burr DB, Komatsubara S, Cao Y, Manabe T, Norimatsu H. The effects of suppressed bone remodeling by bisphosphonates on microdamage accumulation and degree of mineralization in the cortical bone of dog rib. J Bone Miner Metab. 2005;23(suppl):36–42. CrossRef
- Napoli N, Novack D, Armamento-Villareal R. Bisphosphonate-associated femoral fracture: implications for management in patients with malignancies. Osteoporos Int. 2010;21:705–708. CrossRef
- Neviaser AS, Lane JM, Lenart BA, Edobor-Osula F, Lorich DG. Low-energy femoral shaft fractures associated with alendronate use. J Orthop Trauma. 2008;22:346–350. CrossRef
- Odvina CV, Zerwekh JE, Rao DS, Maalouf N, Gottschalk FA, Pak CY. Severely suppressed bone turnover: a potential complication of alendronate therapy. J Clin Endocrinol Metab. 2005;90:1294–1301. CrossRef
- Ott SM. Atraumatic bilateral femur fracture in long-term bisphosphonate use. Comment on Orthopedics. 2009 Aug;32(8). pii: orthosupersite.com/view.asp?rID = 41933. doi:10.3928/01477447-20090624-27. Orthopedics. 2010;33:468.
- Riggs BL, Melton LJ III. The prevention and treatment of osteoporosis. N Engl J Med. 1992;327:620–627. CrossRef
- Sayed-Noor AS, Sjoden GO. Subtrochanteric displaced insufficiency fracture after long-term alendronate therapy: a case report. Acta Orthop. 2008;79:565–567. CrossRef
- Sayed-Noor AS, Sjoden GO. Case reports: two femoral insufficiency fractures after long-term alendronate therapy. Clin Orthop Relat Res. 2009;467:1921–1926. CrossRef
- Somford MP, Geurts GF, den Teuling JW, Thomassen BJ, Draijer WF. Long-term alendronate use not without consequences? Int J Rheumatol. 2009;2009:253432.
- Wells GA, Cranney A, Peterson J, Boucher M, Shea B, Robinson V, Coyle D, Tugwell. Alendronate for the primary and secondary prevention of osteoporotic fractures in postmenopausal women. Cochrane Database Syst Rev. 2008;CD001155.
- Bisphosphonate-associated Femur Fractures Have High Complication Rates with Operative Fixation
Clinical Orthopaedics and Related Research®
Volume 470, Issue 8 , pp 2295-2301
- Cover Date
- Print ISSN
- Online ISSN
- Additional Links
- Industry Sectors
- Author Affiliations
- 1. Orthopedic Trauma Service, Hospital for Special Surgery, 535 East 70th Street, New York, NY, 10021, USA
- 2. New York Presbyterian Hospital, New York, NY, USA
- 3. Weill Medical College of Cornell University, New York, NY, USA