Uzun süre bifosfonat tedavisi alan hastalarda görülen bilateral düşük-enerjili ardışık femur cisim kırıkları

Year 2013, Volume: 47 Issue: 3, 162 - 172, 11.06.2013

Selami Cakmak Mahir Mahirogullari Kenan Keklikci Enes Sari Baran Erdik Osman Rodop

Abstract

Amaç: Bu makale ile bilateral, bifosfonatla ilişkili, düşük enerjili femur cisim kırığı olan hastaların demografik özelliklerinin değerlendirilmesi amaçlandı.
Çalışma planı: Ocak 2008 ila Ocak 2012 tarihleri arasında düşük enerjili femur cisim kırığı olan hastaların kayıtları incelenerek bifosfonatla ilişkili olabilecek olgular saptandı. Postmenopozal osteoporoz tanısı olan, en az 5 yıl süreyle bifosfonat kullanan ve kırıkları öncesinde prodromal ağrısı olan hastalar çalışmaya alındı.
Bulgular: Çalışmaya alınma kriterlerine uyan 5 kadın hasta saptandı. Hastaların hepsinde bilateral, düşük enerjili, ardışık femur cisim kırığı vardı. Kırık yapıları benzerdi ve atipik (lateral kortekste kalınlaşmanın olduğu transvers-kısa oblik kırıklar) idi. Ortalama bifosfonat tedavi süresi 8.6 yıl idi. Ortalama hasta yaşı 76.2 olarak saptandı. Üç hastanın ortalama kırık kaynama süresi 20-28 hafta idi. Diğer iki hastada gecikmiş kaynama veya kaynamama nedeniyle revizyon yapıldı.
Çıkarımlar: Uzun süre (5 yıldan daha uzun) bifosfonat kullanılması, kemik remodelizasyonunun baskılanması ile yakın ilişkili olan artmış kırılganlık nedeniyle yetmezlik kırıklarına yol açabilir. Bifosfonatlar ile atipik düşük enerjili femur cisim kırıkları arasında nedensel bir ilişki henüz gösterilememiş olmakla birlikte bifosfonatların optimal kullanım süresi ve uzun dönem güvenilirliği konusunda endişelerimiz bulunmaktadır.

Keywords

Atipik femur cisim kırığı; bifosfonat; subtrokanterik kırık.

Bilateral low-energy sequential femoral shaft fractures in patients on long-term bisphosphonate therapy

Abstract

Objective: The aim of this study was to evaluate the demographic characteristics of patients with bilateral bisphosphonate-related low-energy femoral shaft fractures.
Methods: The clinical registry was reviewed for patients with bisphosphonate-related low-energy fractures localized at femoral shaft between January 2008 and January 2012. Patients with a diagnosis of postmenopausal osteoporosis, bisphosphonate usage of at least 5 years and prodromal pain prior to fracture were included the study.
Results: Five women met the inclusion criteria. All patients had bilateral low-energy sequential femoral shaft fractures. Fracture patterns were similar and atypical (transverse-short oblique fractures with lateral cortical thickening). Mean period of bisphosphonate treatment was 8.6 years. Mean patient age was 76.2 years. Union time of three patients was between 20 and 28 weeks. The remaining two fractures were revised for delayed union or nonunion.
Conclusion: Long-term (over 5 years) use of bisphosphonates may cause insufficiency fractures due to increased fragility and brittleness which have a close relationship with depressed bone remodeling. While there is still no causal relationship between bisphosphonates and atypical, low-energy femoral shaft fractures, we have some concerns about the optimal usage time and long-term safety of bisphosphonate drugs.

Keywords

Atypical femoral shaft fracture, bisphosphonate, subtrochanteric fracture

References

• Consensus development conference: diagnosis, prophylaxis, and treatment of osteoporosis. Am J Med 1993;94:646-50.
• Melton LJ. Report of the Surgeon General’s Workshop on Osteoporosis and Bone Health: Prevalence and Burden of Illness [Internet]. Department of Health and Human Services. December 12-13, 2002 [cited 2012 Mar 12]. Available from: http://www.ncbi.nlm.nih.gov/books/NBK44687/pdf/TOC.pdf. Johnell O, Kanis JA. An estimate of the worldwide prevalence and disability associated with osteoporotic fractures. Osteoporos Int 2006;17:1726-33.
• Watts NB, Bilezikian JP, Camacho PM, Greenspan SL, Haris ST, Hodgson SF, et al. American Association of Clinical Endocrinologists Medical Guidelines for Clinical Practice for the diagnosis and treatment of postmenopausal osteoporosis. Endocr Pract 2010;16:1-37.
• Devold HM, Doung GM, Tverdal A, Furu K, Meyer HE, Falch JA, et al. Prescription of anti-osteoporosis drugs during 2004-2007 - a nationwide register study in Norway. Eur J Clin Pharmacol 2010;66:299-306.
• Wells GA, Cranney A, Peterson J, Boucher M, Shea B, Robinson V, et al. Alendronate for the primary and secondary prevention of osteoporotic fractures in postmenopausal women. Cochrane Database Syst Rev 2008;1:CD001155.
• Schubert M, Klatte I, Linek W, Müller B, Döring K, Eckelt U, et al. The Saxon bisphosphonate register - therapy and prevention of bisphosphonate-related osteonecrosis of the jaws. Oral Oncol 2012;48:349-54.
• Atik OS, Suluova F, Görmeli G, Yildirim A, Ali AKh. Insufficiency femoral fractures in patients undergoing prolonged alendronate therapy. Eklem Hastalik Cerrahisi 2010; 21:56-59.
• Aydogan NH, Gul D, Ozturk A, Alemdaroglu KB, Kara T, Gultac E. Fractures of the lower limb following bisphosphonate use and their surgical treatment: five case reports. [Article in Turkish] Acta Orthop Traumatol Turc 2011;Suppl 1:12.
• 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;91:2556-61.
• Cheung RK, Leung KK, Lee KC, Chow TC. Sequential non-traumatic femoral shaft fractures in a patient on longterm alendronate. Hong Kong Med J 2007;13:485-9.
• Demiralp B, Ilgan S, Ozgur Karacalioglu A, Cicek EI, Yildrim D, Erler K. Bilateral femoral insuffiency fractures treated with inflatable intramedullary nails: a case report. Arch Orthop Trauma Surg 2007;127:597-601.
• Goh SK, Yang KY, Koh JS, Wong MK, Chua SY, Chua DT, et al. Subtrochanteric insufficiency fractures in patients on alendronate therapy: a caution. J Bone Joint Surg Br 2007; 89:349-53.
• Isaacs JD, Shidiak L, Harris IA, Szomor ZL. Femoral insufficiency fractures associated with prolonged bisphosphonate therapy. Clin Orthop Relat Res 2010;468:3384-92.
• Lenart BA, Lorich DG, Lane JM. Atypical fractures of the femoral diaphysis in postmenopausal women taking alendronate. N Engl J Med 2008;358:1304-6.
• Lenart BA, Neviaser AS, Lyman S, Chang CC, EdoborOsula F, Steele B, et al. Association of low-energy femoral fractures with prolonged bisphosphonate use: a case control study. Osteoporos Int 2009;20:1353-62.
• 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;90:1294-301.
• Sayed-Noor AS, Sjödén GO. Case reports: two femoral insufficiency fractures after long-term alendronate therapy. Clin Orthop Relat Res 2009;467:1921-6.
• Visekruna M, Wilson D, McKiernan FE. Severely suppressed bone turnover and atypical skeletal fragility. J Clin Endocrinol Metab 2008;93:2948-52.
• Bone HG, Hosking D, Devogelaer JP, Tucci JR, Emkey RD, Tonino RP, et al. Ten years’ experience with alendronate for osteoporosis in postmenopausal women. N Engl J Med 2004; 350:1189-99.
• Eastell R, Barton I, Hannon RA, Chines A, Garnero P, Delmas PD. Relationship of early changes in bone resorption to the reduction in fracture risk with risedronate. J Bone Miner Res 2003;18:1051-6.
• Bilezikian JP. Efficacy of bisphosphonates in reducing fracture risk in postmenopausal osteoporosis. Am J Med 2009;122: S14Tonino RP, Meunier PJ, Emkey R, Rodriguez-Portales JA, Menkes CJ, Wasnich RD, et al. Skeletal benefits of alendronate: 7-year treatment of postmenopausal osteoporotic women. Phase III Osteoporosis Treatment Study Group. J Clin Endocrinol Metab 2000;85:3109-15.
• Drake MT, Clarke BL, Khosla S. Bisphosphonates: mechanism of action and role in clinical practice. Mayo Clin Proc 2008;83:1032-45.
• 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; 15:613-20.
• Li J, Mashiba T, Burr DB. Bisphosphonate treatment suppresses not only stochastic remodeling but also the targeted repair of microdamage. Calcif Tissue Int 2001;69:281-6.
• Cao Y, Mori S, Mashiba T, Westmore MS, Ma L, Sato M, et al. Raloxifene, estrogen, and alendronate affect the processes of fracture repair differently in ovariectomized rats. J Bone Miner Res 2002;17:2237-46.
• Armamento-Villareal R, Napoli N, Diemer K, Watkins M, Civitelli R, Teitelbaum S, et al. Bone turnover in bone biopsies of patients with low-energy cortical fractures receiving bisphosphonates: a case series. Calcif Tissue Int 2009;85:37
• Stepan JJ, Burr DB, Pavo I, Sipos A, Michalska D, Li J, et al. Low bone mineral density is associated with bone microdamage accumulation in postmenopausal women with osteoporosis. Bone 2007;41:378-85.
• Sellmeyer DE. Atypical fractures as a potential complication of long-term bisphosphonate therapy. JAMA 2010;304:1480
• Burr DB, Forwood MR, Fyhrie DP, Martin RB, Schaffler MB, Turner CH. Bone microdamage and skeletal fragility in osteoporotic and stress fractures. J Bone Miner Res 1997;12:6
• Mashiba T, Turner CH, Hirano T, Forwood MR, Jacob DS, Johnston CC, et al. Effects of high-dose etidronate treatment on microdamage accumulation and biomechanical properties in beagle bone before occurrence of spontaneous fractures. Bone 2001;29:271-8.
• Bala Y, Depalle B, Farlay D, Douillard T, Meille S, Follet H, et al. Bone micromechanical properties are compromised during long-term alendronate therapy independently of mineralization. J Bone Miner Res 2012;27:825-34.
• Ott SM. What is the optimal duration of bisphosphonate therapy? Cleve Clin J Med 2011;78:619-30.
• Feldman F. Atypical diaphyseal femoral fractures – new aspects. Skeletal Radiol 2012;41:75-81.
• Nieves JW, Cosman F. Atypical subtrochanteric and femoral shaft fractures and possible association with bisphosphonates. Curr Osteoporos Rep 2010;8:34-9.
• Gaeta M, Minutoli F, Vinci S, Salamone I, D’Andrea L, Bitto L, et al. High-resolution CT grading of tibial stress reactions in distance runners. AJR Am J Roentgenol 2006;187:789-93. Mashiba T, Mori S, Burr DB, Komatsubara S, Cao Y, Manabe T, et al. 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;23:36-42.
• Currey JD. Effects of differences in mineralization on the mechanical properties of bone. Philos Trans R Soc Lond B Biol Sci 1984;304:509-18.
• Black DM, Schwartz AV, Ensrud KE, Cauley JA, Levis S, Quandt SA, et al. Effects of continuing or stopping alendronate after 5 years of treatment: the Fracture Intervention Trial Long-term Extension (FLEX): a randomized trial. JAMA 2006;296:2927-38.
• Fleisch H. Bisphosphonates: mechanisms of action. Endocr Rev 1998;19:80-100.
• Gertz BJ, Holland SD, Kline WF, Matuszewski BK, Porras AG. Clinical pharmacology of alendronate sodium. Osteoporos Int 1993;3 Suppl 3:S13-6.
• Ott SM. Long-term safety of bisphosphonates. J Clin Endocrinol Metab 2005;90:1897-9.
• Weil YA, Rivkin G, Safran O, Liebergall M, Foldes AJ. The outcome of surgically treated femur fractures associated with long-term bisphosphonate use. J Trauma 2011;71:186-90.
• 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 2009; 24:1095-102.
• Black DM, Kelly MP, Genant HK, Palermo L, Eastell R, Bucci-Rechtweg C, et al. Bisphosphonates and fractures of the subtrochanteric or diaphyseal femur. N Engl J Med 2010; 362:1761-71.
• Giusti A, Hamdy NA, Dekkers OM, Ramautar SR, Dijkstra S, Papapoulos SE. Atypical fractures and bisphosphonate therapy: a cohort study of patients with femoral fracture with radiographic adjudication of fracture site and features. Bone 2011;48:966-71.
• Kim SY, Schneeweiss S, Katz JN, Levin R, Solomon DH. Oral bisphosphonates and risk of subtrochanteric or diaphyseal femur fractures in a population-based cohort. J Bone Miner Res 2011;26:993-1001.
• Nieves JW, Bilezikian JP, Lane JM, Einhorn TA, Wang Y, Steinbuch M, et al. Fragility fractures of the hip and femur: incidence and patient characteristics. Osteoporos Int 2010; 21:399-408.
• Park-Wyllie LY, Mamdani MM, Juurlink DN, Hawker GA, Gunraj N, Austin PC, et al. Bisphosphonate use and the risk of subtrochanteric or femoral shaft fractures in older women. JAMA 2011;305:783-9.
• Rizzoli R, Akesson K, Bouxsein M, Kanis JA, Napoli N, Papapoulos S, et al. Subtrochanteric fractures after longterm treatment with bisphosphonates: a European Society on Clinical and Economic Aspects of Osteoporosis and Osteoarthritis, and International Osteoporosis Foundation Working Group Report. Osteoporos Int 2011;22:373-90.
• Wang Z, Bhattacharyya T. Trends in incidence of subtrochanteric fragility fractures and bisphosphonate use among the US elderly, 1996-2007. J Bone Miner Res 2011; 26:553-60.
• No authors listed. FDA Drug Safety Communication: safety update for osteoporosis drugs, bisphosphonates, and atypical fractures, 2010 [cited 2011 June 27]. Available from: http://www.fda.gov/drugs/drugsafety/ucm229009.htm.
• Venkatanarasimha N, Miles G, Suresh P. Subtrochanteric femoral insufficiency fractures related to the use of long-term bisphosphonates: a pictorial review. Emerg Radiol 2010;17: 511Iizuka T, Matsukawa M. Potential excessive suppression of bone turnover with long-term oral bisphosphonate therapy in postmenopausal osteoporotic patients. Climacteric 2008; 11:287-95.
• Kanis JA. FRAX: WHO Fracture Risk Assessment Tool [Internet]. World Health Organization Collaborating Centre for Metabolic Bone Diseases, University of Sheffield, UK. [Cited 2012 Feb 22] Available from: http://www.shef.ac.uk/ FRAX