Skip to main content
Top
Published in: Clinical Orthopaedics and Related Research® 12/2010

01-12-2010 | Clinical Research

Femoral Insufficiency Fractures Associated with Prolonged Bisphosphonate Therapy

Authors: Joseph D. Isaacs, MD, Louis Shidiak, MD, Ian A. Harris, MD, PhD, Zoltan L. Szomor, MD, PhD

Published in: Clinical Orthopaedics and Related Research® | Issue 12/2010

Login to get access

Abstract

Background

Emerging evidence has linked the long-term use of bisphosphonates with femoral insufficiency fractures. It has been suggested that the prolonged effect on bone remodeling leads to the accumulation of microfractures and weakening of bone.

Questions/purposes

We investigated the association between bisphosphonate use and femoral insufficiency fractures.

Methods

We evaluated 100 patients with low-energy femoral shaft fractures before and after bisphosphonates became available for use. Twenty-one consecutive patients who presented between January 1995 and February 1997 were compared with 79 consecutive patients who presented between January 2007 and February 2009. The radiographs of all 100 patients were examined for evidence of preexisting insufficiency fractures. We identified insufficiency fractures by a transverse fracture line on the tension side of the femur with lateral cortical thickening immediately adjacent to the fracture. Relevant details from the history were recorded.

Results

Forty-one patients had an underlying femoral insufficiency fracture, all of whom had been receiving bisphosphonate therapy. Among the 21 patients with low-energy femoral fractures before the availability of bisphosphonates, none had insufficiency fractures. Of the 41 patients with insufficiency fractures, 29 (71%) had prodromal pain and 18 (44%) had bilateral insufficiency fractures. Bisphosphonate use was associated (odds ratio greater than 1000) with insufficiency fracture. The mean duration of bisphosphonate use in patients with insufficiency fractures was longer than in patients without fractures (7.1 versus 3.2 years).

Conclusion

Long-term bisphosphonate use is associated with insufficiency fractures of the femoral shaft, which commonly present with prodromal thigh pain and may be bilateral. These fractures were not seen before bisphosphonates became available for use.

Level of Evidence

Level III, therapeutic study. See Guidelines for Authors for a complete description of levels of evidence.
Literature
1.
go back to reference 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. 2010 Apr 10. [Epub ahead of print]. 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. 2010 Apr 10. [Epub ahead of print].
2.
go back to reference Akkus O, Polyakova-Akkus A, Adar F, Schaffler MB. Aging of microstructural compartments in human compact bone. J Bone Miner Res. 2003;18:1012–1019.CrossRefPubMed Akkus O, Polyakova-Akkus A, Adar F, Schaffler MB. Aging of microstructural compartments in human compact bone. J Bone Miner Res. 2003;18:1012–1019.CrossRefPubMed
3.
go back to reference Allen MR. Skeletal accumulation of bisphosphonates: implications for osteoporosis treatment. Expert Opin Drug Metab Toxicol. 2008;4:1371–1378.CrossRefPubMed Allen MR. Skeletal accumulation of bisphosphonates: implications for osteoporosis treatment. Expert Opin Drug Metab Toxicol. 2008;4:1371–1378.CrossRefPubMed
4.
go back to reference Allen MR, Burr DB. Three years of alendronate treatment results in similar levels of vertebral microdamage as after one year of treatment. J Bone Miner Res. 2007;22:1759–1765.CrossRefPubMed Allen MR, Burr DB. Three years of alendronate treatment results in similar levels of vertebral microdamage as after one year of treatment. J Bone Miner Res. 2007;22:1759–1765.CrossRefPubMed
5.
go back to reference 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;39:872–879.CrossRefPubMed 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;39:872–879.CrossRefPubMed
6.
go back to reference Aspenberg P. Bisphosphonate-induced fractures: nature strikes back? Acta Orthop. 2008;79:459–460.CrossRefPubMed Aspenberg P. Bisphosphonate-induced fractures: nature strikes back? Acta Orthop. 2008;79:459–460.CrossRefPubMed
7.
go back to reference Bauer DC, Black D, Ensrud K, Thompson D, Hochberg M, Nevitt M, Musliner T, Freedholm D. Upper gastrointestinal tract safety profile of alendronate: the fracture intervention trial. Arch Intern Med. 2000;160:517–525.CrossRefPubMed Bauer DC, Black D, Ensrud K, Thompson D, Hochberg M, Nevitt M, Musliner T, Freedholm D. Upper gastrointestinal tract safety profile of alendronate: the fracture intervention trial. Arch Intern Med. 2000;160:517–525.CrossRefPubMed
8.
go back to reference Black DM, Cummings SR, Karpf DB, Cauley JA, Thompson DE, Nevitt MC, Bauer DC, Genant HK, Haskell WL, Marcus R, Ott SM, Torner JC, Quandt SA, Reiss TF, Ensrud KE. Randomised trial of effect of alendronate on risk of fracture in women with existing vertebral fractures. Fracture Intervention Trial Research Group. Lancet. 1996;348:1535–1541.CrossRefPubMed Black DM, Cummings SR, Karpf DB, Cauley JA, Thompson DE, Nevitt MC, Bauer DC, Genant HK, Haskell WL, Marcus R, Ott SM, Torner JC, Quandt SA, Reiss TF, Ensrud KE. Randomised trial of effect of alendronate on risk of fracture in women with existing vertebral fractures. Fracture Intervention Trial Research Group. Lancet. 1996;348:1535–1541.CrossRefPubMed
9.
go back to reference Black DM, Reiss TF, Nevitt MC, Cauley J, Karpf D, Cummings SR. Design of the Fracture Intervention Trial. Osteoporos Int. 1993;3(suppl 3):S29–39.CrossRefPubMed Black DM, Reiss TF, Nevitt MC, Cauley J, Karpf D, Cummings SR. Design of the Fracture Intervention Trial. Osteoporos Int. 1993;3(suppl 3):S29–39.CrossRefPubMed
10.
go back to reference Black DM, Schwartz AV, Ensrud KE, Cauley JA, Levis S, Quandt SA, Satterfield S, Wallace RB, Bauer DC, Palermo L, Wehren LE, Lombardi A, Santora AC, Cummings SR; FLEX Research Group. Effects of continuing or stopping alendronate after 5 years of treatment: the Fracture Intervention Trial Long-term Extension (FLEX): a randomized trial. JAMA. 2006;296:2927–2938.CrossRefPubMed Black DM, Schwartz AV, Ensrud KE, Cauley JA, Levis S, Quandt SA, Satterfield S, Wallace RB, Bauer DC, Palermo L, Wehren LE, Lombardi A, Santora AC, Cummings SR; FLEX Research Group. Effects of continuing or stopping alendronate after 5 years of treatment: the Fracture Intervention Trial Long-term Extension (FLEX): a randomized trial. JAMA. 2006;296:2927–2938.CrossRefPubMed
11.
go back to reference Black DM, Thompson DE, Bauer DC, Ensrud K, Musliner T, Hochberg MC, Nevitt MC, Suryawanshi S, Cummings SR; Fracture Intervention Trial. Fracture risk reduction with alendronate in women with osteoporosis: the Fracture Intervention Trial. FIT Research Group. J Clin Endocrinol Metab. 2000;85:4118–4124.CrossRefPubMed Black DM, Thompson DE, Bauer DC, Ensrud K, Musliner T, Hochberg MC, Nevitt MC, Suryawanshi S, Cummings SR; Fracture Intervention Trial. Fracture risk reduction with alendronate in women with osteoporosis: the Fracture Intervention Trial. FIT Research Group. J Clin Endocrinol Metab. 2000;85:4118–4124.CrossRefPubMed
12.
go back to reference Boivin G, Farlay D, Bala Y, Doublier A, Meunier PJ, Delmas PD. Influence of remodeling on the mineralization of bone tissue. Osteoporos Int. 2009;20:1023–1026.CrossRefPubMed Boivin G, Farlay D, Bala Y, Doublier A, Meunier PJ, Delmas PD. Influence of remodeling on the mineralization of bone tissue. Osteoporos Int. 2009;20:1023–1026.CrossRefPubMed
13.
go back to reference Boivin G, Meunier PJ. Changes in bone remodeling rate influence the degree of mineralization of bone. Connect Tissue Res. 2002;43:535–537.PubMed Boivin G, Meunier PJ. Changes in bone remodeling rate influence the degree of mineralization of bone. Connect Tissue Res. 2002;43:535–537.PubMed
14.
go back to reference Boivin GY, Chavassieux PM, Santora AC, Yates J, Meunier PJ. Alendronate increases bone strength by increasing the mean degree of mineralization of bone tissue in osteoporotic women. Bone. 2000;27:687–694.CrossRefPubMed Boivin GY, Chavassieux PM, Santora AC, Yates J, Meunier PJ. Alendronate increases bone strength by increasing the mean degree of mineralization of bone tissue in osteoporotic women. Bone. 2000;27:687–694.CrossRefPubMed
15.
go back to reference Bone HG, Hosking D, Devogelaer JP, Tucci JR, Emkey RD, Tonino RP, Rodriguez-Portales JA, Downs RW, Gupta J, Santora AC, Liberman UA; Alendronate Phase III Osteoporosis Treatment Study Group. Ten years’ experience with alendronate for osteoporosis in postmenopausal women. N Engl J Med. 2004;350:1189–1199.CrossRefPubMed Bone HG, Hosking D, Devogelaer JP, Tucci JR, Emkey RD, Tonino RP, Rodriguez-Portales JA, Downs RW, Gupta J, Santora AC, Liberman UA; Alendronate Phase III Osteoporosis Treatment Study Group. Ten years’ experience with alendronate for osteoporosis in postmenopausal women. N Engl J Med. 2004;350:1189–1199.CrossRefPubMed
16.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
17.
go back to reference Chavassieux P, Seeman E, Delmas PD. Insights into material and structural basis of bone fragility from diseases associated with fractures: how determinants of the biomechanical properties of bone are compromised by disease. Endocr Rev. 2007;28:151–164.CrossRefPubMed Chavassieux P, Seeman E, Delmas PD. Insights into material and structural basis of bone fragility from diseases associated with fractures: how determinants of the biomechanical properties of bone are compromised by disease. Endocr Rev. 2007;28:151–164.CrossRefPubMed
18.
go back to reference Ciarelli TE, Fyhrie DP, Parfitt AM. Effects of vertebral bone fragility and bone formation rate on the mineralization levels of cancellous bone from white females. Bone. 2003;32:311–315.CrossRefPubMed Ciarelli TE, Fyhrie DP, Parfitt AM. Effects of vertebral bone fragility and bone formation rate on the mineralization levels of cancellous bone from white females. Bone. 2003;32:311–315.CrossRefPubMed
19.
go back to reference Cummings SR, Black DM, Thompson DE, Applegate WB, Barrett-Connor E, Musliner TA, Palermo L, Prineas R, Rubin SM, Scott JC, Vogt T, Wallace R, Yates AJ, LaCroix AZ. 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;280:2077–2082.CrossRefPubMed Cummings SR, Black DM, Thompson DE, Applegate WB, Barrett-Connor E, Musliner TA, Palermo L, Prineas R, Rubin SM, Scott JC, Vogt T, Wallace R, Yates AJ, LaCroix AZ. 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;280:2077–2082.CrossRefPubMed
20.
go back to reference Currey JD. Effects of differences in mineralization on the mechanical properties of bone. Philos Trans R Soc Lond B Biol Sci. 1984;304:509–518.CrossRef Currey JD. Effects of differences in mineralization on the mechanical properties of bone. Philos Trans R Soc Lond B Biol Sci. 1984;304:509–518.CrossRef
21.
go back to reference Curtis JR, Westfall AO, Cheng H, Delzell E, Saag KG. Risk of hip fracture after bisphosphonate discontinuation: implications for a drug holiday. Osteoporos Int. 2008;19:1613–1620.CrossRefPubMed Curtis JR, Westfall AO, Cheng H, Delzell E, Saag KG. Risk of hip fracture after bisphosphonate discontinuation: implications for a drug holiday. Osteoporos Int. 2008;19:1613–1620.CrossRefPubMed
22.
go back to reference Dobnig H, Stepan JJ, Burr DB, Li J, Michalska D, Sipos A, Petto H, Fahrleitner-Pammer A, Pavo I. Teriparatide reduces bone microdamage accumulation in postmenopausal women previously treated with alendronate. J Bone Miner Res. 2009;24:1998–2006.CrossRefPubMed Dobnig H, Stepan JJ, Burr DB, Li J, Michalska D, Sipos A, Petto H, Fahrleitner-Pammer A, Pavo I. Teriparatide reduces bone microdamage accumulation in postmenopausal women previously treated with alendronate. J Bone Miner Res. 2009;24:1998–2006.CrossRefPubMed
23.
go back to reference 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;21:701–703.CrossRefPubMed 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;21:701–703.CrossRefPubMed
24.
go back to reference Ensrud KE, Barrett-Connor EL, Schwartz A, Santora AC, Bauer DC, Suryawanshi S, Feldstein A, Haskell WL, Hochberg MC, Torner JC, Lombardi A, Black DM; Fracture Intervention Trial Long-Term Extension Research Group. Randomized trial of effect of alendronate continuation versus discontinuation in women with low BMD: results from the Fracture Intervention Trial long-term extension. J Bone Miner Res. 2004;19:1259–1269.CrossRefPubMed Ensrud KE, Barrett-Connor EL, Schwartz A, Santora AC, Bauer DC, Suryawanshi S, Feldstein A, Haskell WL, Hochberg MC, Torner JC, Lombardi A, Black DM; Fracture Intervention Trial Long-Term Extension Research Group. Randomized trial of effect of alendronate continuation versus discontinuation in women with low BMD: results from the Fracture Intervention Trial long-term extension. J Bone Miner Res. 2004;19:1259–1269.CrossRefPubMed
25.
go back to reference Garnero P, Shih WJ, Gineyts E, Karpf DB, Delmas PD. Comparison of new biochemical markers of bone turnover in late postmenopausal osteoporotic women in response to alendronate treatment. J Clin Endocrinol Metab. 1994;79:1693–1700.CrossRefPubMed Garnero P, Shih WJ, Gineyts E, Karpf DB, Delmas PD. Comparison of new biochemical markers of bone turnover in late postmenopausal osteoporotic women in response to alendronate treatment. J Clin Endocrinol Metab. 1994;79:1693–1700.CrossRefPubMed
26.
go back to reference Goh SK, 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.CrossRefPubMed Goh SK, 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.CrossRefPubMed
27.
go back to reference Hirano T, Turner CH, Forwood MR, Johnston CC, Burr DB. Does suppression of bone turnover impair mechanical properties by allowing microdamage accumulation? Bone. 2000;27:13–20.CrossRefPubMed Hirano T, Turner CH, Forwood MR, Johnston CC, Burr DB. Does suppression of bone turnover impair mechanical properties by allowing microdamage accumulation? Bone. 2000;27:13–20.CrossRefPubMed
28.
go back to reference Iwamoto J, Takeda T, Sato Y. Efficacy and safety of alendronate and risedronate for postmenopausal osteoporosis. Curr Med Res Opin. 2006;22:919–928.CrossRefPubMed Iwamoto J, Takeda T, Sato Y. Efficacy and safety of alendronate and risedronate for postmenopausal osteoporosis. Curr Med Res Opin. 2006;22:919–928.CrossRefPubMed
29.
go back to reference Jobke B, Pfeifer M, Minne HW. Teriparatide following bisphosphonates: initial and long-term effects on microarchitecture and bone remodeling at the human iliac crest. Connect Tissue Res. 2009;50:46–54.CrossRefPubMed Jobke B, Pfeifer M, Minne HW. Teriparatide following bisphosphonates: initial and long-term effects on microarchitecture and bone remodeling at the human iliac crest. Connect Tissue Res. 2009;50:46–54.CrossRefPubMed
30.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
31.
go back to reference Komatsubara S, Mori S, Mashiba T, Ito M, Li J, Kaji Y, Akiyama T, Miyamoto K, Cao Y, Kawanishi J, Norimatsu H. Long-term treatment of incadronate disodium accumulates microdamage but improves the trabecular bone microarchitecture in dog vertebra. J Bone Miner Res. 2003;18:512–520.CrossRefPubMed Komatsubara S, Mori S, Mashiba T, Ito M, Li J, Kaji Y, Akiyama T, Miyamoto K, Cao Y, Kawanishi J, Norimatsu H. Long-term treatment of incadronate disodium accumulates microdamage but improves the trabecular bone microarchitecture in dog vertebra. J Bone Miner Res. 2003;18:512–520.CrossRefPubMed
32.
go back to reference Komatsubara S, Mori S, Mashiba T, Li J, Nonaka K, Kaji Y, Akiyama T, Miyamoto K, Cao Y, Kawanishi J, Norimatsu H. Suppressed bone turnover by long-term bisphosphonate treatment accumulates microdamage but maintains intrinsic material properties in cortical bone of dog rib. J Bone Miner Res. 2004;19:999–1005.CrossRefPubMed Komatsubara S, Mori S, Mashiba T, Li J, Nonaka K, Kaji Y, Akiyama T, Miyamoto K, Cao Y, Kawanishi J, Norimatsu H. Suppressed bone turnover by long-term bisphosphonate treatment accumulates microdamage but maintains intrinsic material properties in cortical bone of dog rib. J Bone Miner Res. 2004;19:999–1005.CrossRefPubMed
33.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
34.
go back to reference Lanza F, Sahba B, Schwartz H, Winograd S, Torosis J, Quan H, Reyes R, Musliner T, Daifotis A, Leung A. The upper GI safety and tolerability of oral alendronate at a dose of 70 milligrams once weekly: a placebo-controlled endoscopy study. Am J Gastroenterol. 2002;97:58–64.CrossRefPubMed Lanza F, Sahba B, Schwartz H, Winograd S, Torosis J, Quan H, Reyes R, Musliner T, Daifotis A, Leung A. The upper GI safety and tolerability of oral alendronate at a dose of 70 milligrams once weekly: a placebo-controlled endoscopy study. Am J Gastroenterol. 2002;97:58–64.CrossRefPubMed
35.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
36.
go back to reference 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. Osteoporos Int. 2009;20:1353–1362.CrossRefPubMed 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. Osteoporos Int. 2009;20:1353–1362.CrossRefPubMed
37.
go back to reference Li J, Mashiba T, Burr DB. Bisphosphonate treatment suppresses not only stochastic remodeling but also the targeted repair of microdamage. Calcif Tissue Int. 2001;69:281–286.CrossRefPubMed Li J, Mashiba T, Burr DB. Bisphosphonate treatment suppresses not only stochastic remodeling but also the targeted repair of microdamage. Calcif Tissue Int. 2001;69:281–286.CrossRefPubMed
38.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
39.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
40.
go back to reference Lufkin EG, Wahner HW, O’Fallon WM, Hodgson SF, Kotowicz MA, Lane AW, Judd HL, Caplan RH, Riggs BL. Treatment of postmenopausal osteoporosis with transdermal estrogen. Ann Intern Med. 1992;117:1–9.PubMed Lufkin EG, Wahner HW, O’Fallon WM, Hodgson SF, Kotowicz MA, Lane AW, Judd HL, Caplan RH, Riggs BL. Treatment of postmenopausal osteoporosis with transdermal estrogen. Ann Intern Med. 1992;117:1–9.PubMed
41.
go back to reference Mashiba T, Hirano T, Turner CH, Forwood MR, Johnston CC, Burr DB. Suppressed bone turnover by bisphosphonates increases microdamage accumulation and reduces some biomechanical properties in dog rib. J Bone Miner Res. 2000;15:613–620.CrossRefPubMed Mashiba T, Hirano T, Turner CH, Forwood MR, Johnston CC, Burr DB. Suppressed bone turnover by bisphosphonates increases microdamage accumulation and reduces some biomechanical properties in dog rib. J Bone Miner Res. 2000;15:613–620.CrossRefPubMed
42.
go back to reference Mashiba T, Turner CH, Hirano T, Forwood MR, Johnston CC, Burr DB. Effects of suppressed bone turnover by bisphosphonates on microdamage accumulation and biomechanical properties in clinically relevant skeletal sites in beagles. Bone. 2001;28:524–531.CrossRefPubMed Mashiba T, Turner CH, Hirano T, Forwood MR, Johnston CC, Burr DB. Effects of suppressed bone turnover by bisphosphonates on microdamage accumulation and biomechanical properties in clinically relevant skeletal sites in beagles. Bone. 2001;28:524–531.CrossRefPubMed
43.
go back to reference McClung MR, Geusens P, Miller PD, Zippel H, Bensen WG, Roux C, Adami S, Fogelman I, Diamond T, Eastell R, Meunier PJ, Reginster JY; Hip Intervention Program Study Group. Effect of risedronate on the risk of hip fracture in elderly women. Hip Intervention Program Study Group. N Engl J Med. 2001;344:333–340.CrossRefPubMed McClung MR, Geusens P, Miller PD, Zippel H, Bensen WG, Roux C, Adami S, Fogelman I, Diamond T, Eastell R, Meunier PJ, Reginster JY; Hip Intervention Program Study Group. Effect of risedronate on the risk of hip fracture in elderly women. Hip Intervention Program Study Group. N Engl J Med. 2001;344:333–340.CrossRefPubMed
44.
go back to reference Napoli N, Novack D, Armamento-Villareal R. Bisphosphonate-associated femoral fracture: implications for management in patients with malignancies. Osteoporos Int. 2010;21:705–708.CrossRefPubMed Napoli N, Novack D, Armamento-Villareal R. Bisphosphonate-associated femoral fracture: implications for management in patients with malignancies. Osteoporos Int. 2010;21:705–708.CrossRefPubMed
45.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
46.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
47.
go back to reference Orwoll E, Ettinger M, Weiss S, Miller P, Kendler D, Graham J, Adami S, Weber K, Lorenc R, Pietschmann P, Vandormael K, Lombardi A. Alendronate for the treatment of osteoporosis in men. N Engl J Med. 2000;343:604–610.CrossRefPubMed Orwoll E, Ettinger M, Weiss S, Miller P, Kendler D, Graham J, Adami S, Weber K, Lorenc R, Pietschmann P, Vandormael K, Lombardi A. Alendronate for the treatment of osteoporosis in men. N Engl J Med. 2000;343:604–610.CrossRefPubMed
48.
go back to reference Ott SM. Atraumatic bilateral femur fracture in long-term bisphosphonate use. Orthopedics. 2020;33:468. Ott SM. Atraumatic bilateral femur fracture in long-term bisphosphonate use. Orthopedics. 2020;33:468.
49.
50.
go back to reference Pak CY, Sakhaee K, Adams-Huet B, Piziak V, Peterson RD, Poindexter JR. Treatment of postmenopausal osteoporosis with slow-release sodium fluoride: final report of a randomized controlled trial. Ann Intern Med. 1995;123:401–408.PubMed Pak CY, Sakhaee K, Adams-Huet B, Piziak V, Peterson RD, Poindexter JR. Treatment of postmenopausal osteoporosis with slow-release sodium fluoride: final report of a randomized controlled trial. Ann Intern Med. 1995;123:401–408.PubMed
51.
go back to reference Papapoulos SE, Quandt SA, Liberman UA, Hochberg MC, Thompson DE. Meta-analysis of the efficacy of alendronate for the prevention of hip fractures in postmenopausal women. Osteoporos Int. 2005;16:468–474.CrossRefPubMed Papapoulos SE, Quandt SA, Liberman UA, Hochberg MC, Thompson DE. Meta-analysis of the efficacy of alendronate for the prevention of hip fractures in postmenopausal women. Osteoporos Int. 2005;16:468–474.CrossRefPubMed
52.
go back to reference Pols HA, Felsenberg D, Hanley DA, Stepan J, Munoz-Torres M, Wilkin TJ, Qin-sheng G, Galich AM, Vandormael K, Yates AJ, Stych B. Multinational, placebo-controlled, randomized trial of the effects of alendronate on bone density and fracture risk in postmenopausal women with low bone mass: results of the FOSIT study. Fosamax International Trial Study Group. Osteoporos Int. 1999;9:461–468.CrossRefPubMed Pols HA, Felsenberg D, Hanley DA, Stepan J, Munoz-Torres M, Wilkin TJ, Qin-sheng G, Galich AM, Vandormael K, Yates AJ, Stych B. Multinational, placebo-controlled, randomized trial of the effects of alendronate on bone density and fracture risk in postmenopausal women with low bone mass: results of the FOSIT study. Fosamax International Trial Study Group. Osteoporos Int. 1999;9:461–468.CrossRefPubMed
53.
go back to reference Roschger P, Rinnerthaler S, Yates J, Rodan GA, Fratzl P, Klaushofer K. Alendronate increases degree and uniformity of mineralization in cancellous bone and decreases the porosity in cortical bone of osteoporotic women. Bone. 2001;29:185–191.CrossRefPubMed Roschger P, Rinnerthaler S, Yates J, Rodan GA, Fratzl P, Klaushofer K. Alendronate increases degree and uniformity of mineralization in cancellous bone and decreases the porosity in cortical bone of osteoporotic women. Bone. 2001;29:185–191.CrossRefPubMed
54.
go back to reference Rossini M, Gatti D, Zamberlan N, Braga V, Dorizzi R, Adami S. Long-term effects of a treatment course with oral alendronate of postmenopausal osteoporosis. J Bone Miner Res. 1994;9:1833–1837.CrossRefPubMed Rossini M, Gatti D, Zamberlan N, Braga V, Dorizzi R, Adami S. Long-term effects of a treatment course with oral alendronate of postmenopausal osteoporosis. J Bone Miner Res. 1994;9:1833–1837.CrossRefPubMed
55.
go back to reference Saito M, Marumo K. Collagen cross-links as a determinant of bone quality: a possible explanation for bone fragility in aging, osteoporosis, and diabetes mellitus. Osteoporos Int. 2010;21:195–214.CrossRefPubMed Saito M, Marumo K. Collagen cross-links as a determinant of bone quality: a possible explanation for bone fragility in aging, osteoporosis, and diabetes mellitus. Osteoporos Int. 2010;21:195–214.CrossRefPubMed
56.
go back to reference Sayed-Noor AS, Sjoden GO. Subtrochanteric displaced insufficiency fracture after long-term alendronate therapy: a case report. Acta Orthop. 2008;79:565–567.CrossRefPubMed Sayed-Noor AS, Sjoden GO. Subtrochanteric displaced insufficiency fracture after long-term alendronate therapy: a case report. Acta Orthop. 2008;79:565–567.CrossRefPubMed
57.
go back to reference Sayed-Noor AS, Sjoden GO. Case reports: two femoral insufficiency fractures after long-term alendronate therapy. Clin Orthop Relat Res. 2009;467:1921–1926.CrossRefPubMed Sayed-Noor AS, Sjoden GO. Case reports: two femoral insufficiency fractures after long-term alendronate therapy. Clin Orthop Relat Res. 2009;467:1921–1926.CrossRefPubMed
58.
go back to reference Schneider JP. Should bisphosphonates be continued indefinitely? An unusual fracture in a healthy woman on long-term alendronate. Geriatrics. 2006;61:31–33.PubMed Schneider JP. Should bisphosphonates be continued indefinitely? An unusual fracture in a healthy woman on long-term alendronate. Geriatrics. 2006;61:31–33.PubMed
59.
go back to reference Schneider JP. Bisphosphonates and low-impact femoral fractures: current evidence on alendronate-fracture risk. Geriatrics. 2009;64:18–23.PubMed Schneider JP. Bisphosphonates and low-impact femoral fractures: current evidence on alendronate-fracture risk. Geriatrics. 2009;64:18–23.PubMed
60.
go back to reference Sloan AV, Martin JR, Li S, Li J. Parathyroid hormone and bisphosphonate have opposite effects on stress fracture repair. Bone. 2020;47:235–240.CrossRef Sloan AV, Martin JR, Li S, Li J. Parathyroid hormone and bisphosphonate have opposite effects on stress fracture repair. Bone. 2020;47:235–240.CrossRef
61.
go back to reference Stock JL, Bell NH, Chesnut CH 3rd, Ensrud KE, Genant HK, Harris ST, McClung MR, Singer FR, Yood RA, Pryor-Tillotson S, Wei L, Santora AC II. Increments in bone mineral density of the lumbar spine and hip and suppression of bone turnover are maintained after discontinuation of alendronate in postmenopausal women. Am J Med. 1997;103:291–297.CrossRefPubMed Stock JL, Bell NH, Chesnut CH 3rd, Ensrud KE, Genant HK, Harris ST, McClung MR, Singer FR, Yood RA, Pryor-Tillotson S, Wei L, Santora AC II. Increments in bone mineral density of the lumbar spine and hip and suppression of bone turnover are maintained after discontinuation of alendronate in postmenopausal women. Am J Med. 1997;103:291–297.CrossRefPubMed
62.
go back to reference Tang SY, Allen MR, Phipps R, Burr DB, Vashishth D. Changes in non-enzymatic glycation and its association with altered mechanical properties following 1-year treatment with risedronate or alendronate. Osteoporos Int. 2009;20:887–894.CrossRefPubMed Tang SY, Allen MR, Phipps R, Burr DB, Vashishth D. Changes in non-enzymatic glycation and its association with altered mechanical properties following 1-year treatment with risedronate or alendronate. Osteoporos Int. 2009;20:887–894.CrossRefPubMed
63.
go back to reference Tonino RP, Meunier PJ, Emkey R, Rodriguez-Portales JA, Menkes CJ, Wasnich RD, Bone HG, Santora AC, Wu M, Desai R, Ross PD. Skeletal benefits of alendronate: 7-year treatment of postmenopausal osteoporotic women. Phase III Osteoporosis Treatment Study Group. J Clin Endocrinol Metab. 2000;85:3109–3115.CrossRefPubMed Tonino RP, Meunier PJ, Emkey R, Rodriguez-Portales JA, Menkes CJ, Wasnich RD, Bone HG, Santora AC, Wu M, Desai R, Ross PD. Skeletal benefits of alendronate: 7-year treatment of postmenopausal osteoporotic women. Phase III Osteoporosis Treatment Study Group. J Clin Endocrinol Metab. 2000;85:3109–3115.CrossRefPubMed
64.
go back to reference Unal E, Abaci A, Bober E, Buyukgebiz A. Efficacy and safety of oral alendronate treatment in children and adolescents with osteoporosis. J Pediatr Endocrinol Metab. 2006;19:523–528.PubMed Unal E, Abaci A, Bober E, Buyukgebiz A. Efficacy and safety of oral alendronate treatment in children and adolescents with osteoporosis. J Pediatr Endocrinol Metab. 2006;19:523–528.PubMed
65.
go back to reference Visekruna M, Wilson D, McKiernan FE. Severely suppressed bone turnover and atypical skeletal fragility. J Clin Endocrinol Metab. 2008;93:2948–2952.CrossRefPubMed Visekruna M, Wilson D, McKiernan FE. Severely suppressed bone turnover and atypical skeletal fragility. J Clin Endocrinol Metab. 2008;93:2948–2952.CrossRefPubMed
66.
go back to reference Watts NB, Harris ST, Genant HK, Wasnich RD, Miller PD, Jackson RD, Licata AA, Ross P, Woodson GC 3rd, Yanover MJ, et al. Intermittent cyclical etidronate treatment of postmenopausal osteoporosis. N Engl J Med. 1990;323:73–79.CrossRefPubMed Watts NB, Harris ST, Genant HK, Wasnich RD, Miller PD, Jackson RD, Licata AA, Ross P, Woodson GC 3rd, Yanover MJ, et al. Intermittent cyclical etidronate treatment of postmenopausal osteoporosis. N Engl J Med. 1990;323:73–79.CrossRefPubMed
67.
go back to reference Whyte MP, Wenkert D, Clements KL, McAlister WH, Mumm S. Bisphosphonate-induced osteopetrosis. N Engl J Med. 2003;349:457–463.CrossRefPubMed Whyte MP, Wenkert D, Clements KL, McAlister WH, Mumm S. Bisphosphonate-induced osteopetrosis. N Engl J Med. 2003;349:457–463.CrossRefPubMed
68.
go back to reference Yoon RS, Beebe KS, Benevenia J. Prophylactic bilateral intramedullary femoral nails for bisphosphonate-associated signs of impending subtrochanteric hip fracture. Orthopedics. 2010;16:267–270. Yoon RS, Beebe KS, Benevenia J. Prophylactic bilateral intramedullary femoral nails for bisphosphonate-associated signs of impending subtrochanteric hip fracture. Orthopedics. 2010;16:267–270.
Metadata
Title
Femoral Insufficiency Fractures Associated with Prolonged Bisphosphonate Therapy
Authors
Joseph D. Isaacs, MD
Louis Shidiak, MD
Ian A. Harris, MD, PhD
Zoltan L. Szomor, MD, PhD
Publication date
01-12-2010
Publisher
Springer-Verlag
Published in
Clinical Orthopaedics and Related Research® / Issue 12/2010
Print ISSN: 0009-921X
Electronic ISSN: 1528-1132
DOI
https://doi.org/10.1007/s11999-010-1535-x

Other articles of this Issue 12/2010

Clinical Orthopaedics and Related Research® 12/2010 Go to the issue

Symposium: Papers Presented at the 2009 Closed Meeting of the International Hip Society

Elevation of the Femur in THA Through a Direct Anterior Approach: Cadaver and Clinical Studies

Symposium: Papers Presented at the 2009 Closed Meeting of the International Hip Society

Cemented Hip Designs are a Reasonable Option in Young Patients

Symposium: Papers Presented at the 2009 Closed Meeting of the International Hip Society

Constrained Liner in Neurologic or Cognitively Impaired Patients Undergoing Primary THA

Symposium: Papers Presented at the 2009 Closed Meeting of the International Hip Society

Combining C-reactive Protein and Interleukin-6 May Be Useful to Detect Periprosthetic Hip Infection

Symposium: Papers Presented at the 2009 Closed Meeting of the International Hip Society

The Classic: The Bonding of Prostheses to Bone by Cement