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

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Abstract

Summary

A systematic review of eight ulnar fractures in seven patients with bisphosphonate therapy was performed to describe the characteristics and predisposing factors. The proximal ulna is likely to be fractured, especially in the dominant limb of elderly female patients using walking aids after 7 to 15 years of bisphosphonate use.

Introduction

Long-term bisphosphonate use has been suggested to result in decreased bone remodelling and increased risk of atypical fractures. While the relationship between bisphosphonate use and atypical femoral fractures has been extensively studied, there is relative rarity and unawareness of these fractures in the forearm. We conducted a systematic review of existing case reports to better describe the characteristics and predisposing factors for fractures occurring in patients with bisphosphonate therapy.

Methods

The systematic review was conducted according to PRISMA guidelines. All studies with ulnar fractures in individuals with history of bisphosphonate use were included, with data extracted and analysed in totality.

Results

Seven patients with eight fractures are included. Predisposing factors include elderly females requiring walking aids. There is a propensity for the proximal ulna to be fractured, especially in the dominant limb used for ambulation or transfer. All patients were on bisphosphonate for 7 to 15 years. All fractures were atraumatic, non-comminuted, transverse in configuration, had localised periosteal or endosteal thickening at the fracture site and generalised cortical thickening of the diaphysis.

Conclusion

Ulnar fractures in patients with bisphosphonate therapy demonstrate features similar to those described for atypical femoral fractures, suggesting that these fractures could also possibly be due to bisphosphonate use. However, the ulna appears to be able to tolerate longer periods of alendronate use prior to fracture development. The mechanism and characteristics of these fractures additionally suggest the presence of repetitive stress that accumulates over time due to suppressed bone remodelling in patients on bisphosphonates, eventually resulting in these fractures.

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References

  1. Black DM, Bauer DC, Schwartz AV, Cummings SR, Rosen CJ (2012) Continuing bisphosphonate treatment for osteoporosis—for whom and for how long? N Engl J Med 366:2051–2053

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  2. Whitaker M, Guo J, Kehoe T, Benson G (2012) Bisphosphonates for osteoporosis—where do we go from here? N Engl J Med 366:2048–2051

    Article  CAS  PubMed  Google Scholar 

  3. Giusti A, Hamdy NA, Papapoulos SE (2010) Atypical fractures of the femur and bisphosphonate therapy: a systematic review of case/case series studies. Bone 47(2):169–180

    Article  CAS  PubMed  Google Scholar 

  4. Seraphim A, Al-Hadithy N, Mordecai SC, Al-Nammari S (2012) Do bisphosphonates cause femoral insufficiency fractures? J Orthop Traumatol 13(4):171–177

    Article  PubMed Central  PubMed  Google Scholar 

  5. Gasser AB, Morgan DB, Fleisch HA, Richelle LJ (1972) The influence of two diphosphonates on calcium metabolism in the rat. Clin Sci 43(1):31–45

    CAS  PubMed  Google Scholar 

  6. Tang ZH, Kumar VP (2011) Alendronate-associated ulnar and tibial fractures: a case report. J Orthop Surg (Hong Kong) 19(3):370–372

    Google Scholar 

  7. Edwards BJ, Bunta AD, Lane J, Odvina C, Rao DS, Raisch DW, McKoy JM, Omar I, Belknap SM, Garg V, Hahr AJ, Samaras AT, Fisher MJ, West DP, Langman CB, Stern PH (2013) Bisphosphonates and nonhealing femoral fractures: analysis of the FDA Adverse Event Reporting System (FAERS) and international safety efforts: a systematic review from the Research on Adverse Drug Events And Reports (RADAR) project. J Bone Joint Surg Am 95(4):297–307

    Article  PubMed Central  PubMed  Google Scholar 

  8. Jamal SA, Dion N, Ste-Marie LG (2011) Atypical femoral fractures and bone turnover. N Engl J Med 365(13):1261–1262

    Article  CAS  PubMed  Google Scholar 

  9. Mashiba T, Hirano T, Turner CH, Forwood MR, Johnston CC, Burr DB (2000) Suppressed bone turnover by bisphosphonates increases microdamage accumulation and reduces some biomechanical properties in dog rib. J Bone Miner Res 15(4):613–620

    Article  CAS  PubMed  Google Scholar 

  10. Moon J, Bither N, Lee T (2013) Atypical forearm fractures associated with long-term use of bisphosphonate. Arch Orthop Trauma Surg 133(7):889–892

    Article  PubMed  Google Scholar 

  11. Shane E, Burr D, Abrahamsen B, Adler RA, Brown TD, Cheung AM, Cosman F, Curtis JR, Dell R, Dempster DW, Ebeling PR, Einhorn TA, Genant HK, Geusens P, Klaushofer K, Lane JM, McKiernan F, McKinney R, Ng A, Nieves J, O’Keefe R, Papapoulos S, Howe TS, van der Meulen MC, Weinstein RS, Whyte MP (2014) 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 29(1):1–23

    Article  PubMed  Google Scholar 

  12. Breglia MD, Carter JD (2010) Atypical insufficiency fracture of the tibia associated with long-term bisphosphonate therapy. J Clin Rheumatol 16:76–78

    Article  PubMed  Google Scholar 

  13. Imai K, Yamamoto S, Anamizu Y, Horiuchi T (2007) Pelvic insufficiency fracture associated with severe suppression of bone turnover by alendronate therapy. J Bone Miner Metab 25:333–336

    Article  PubMed  Google Scholar 

  14. Bjørgul K, Reigstad A (2011) Atypical fracture of the ulna associated with alendronate use. Acta Orthop 82(6):761–763

    Article  PubMed Central  PubMed  Google Scholar 

  15. Stathopoulos KD, Kosmidis C, Lyritis GP (2011) Atypical fractures of the femur and ulna and complications of fracture healing in a 76-year-old woman with Sjögren’s syndrome. J Musculoskelet Neuronal Interact 11(2):208–211, quiz 211

    CAS  PubMed  Google Scholar 

  16. Ang BF, Koh JS, Ng AC, Howe TS (2013) Bilateral ulna fractures associated with bisphosphonate therapy. Osteoporos Int 24(4):1523–1525

    Article  CAS  PubMed  Google Scholar 

  17. Osada R, Zukawa M, Kimura T (2014) Atypical ulnar fracture associated with long-term bisphosphonate use. J Orthop Sci. doi:10.1007/s00776-014-0589-0

  18. Chiang GS, Koh KW, Chong TW, Tan BY (2014) Stress fracture of the ulna associated with bisphosphonate therapy and use of walking aid. Osteoporos Int 25(8):2151–2154. doi:10.1007/s00198-014-2739-9

    Article  Google Scholar 

  19. Mashiba T, Mori S, Burr DB, Komatsubara S, Cao Y, Manabe T, Norimatsu H (2005) 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 23(Suppl):36–42

    Article  CAS  PubMed  Google Scholar 

  20. Somford MP, Draijer FW, Thomassen BJ, Chavassieux PM, Boivin G, Papapoulos SE (2009) Bilateral fractures of the femur diaphysis in a patient with rheumatoid arthritis on long-term treatment with alendronate: clues to the mechanism of increased bone fragility. J Bone Miner Res 24(10):1736–1740

    Article  PubMed  Google Scholar 

  21. Benford HL, McGowan NW, Helfrich MH, Nuttall ME, Rogers MJ (2001) Visualization of bisphosphonate-induced caspase-3 activity in apoptotic osteoclasts in vitro. Bone 28(5):465–473

    Article  CAS  PubMed  Google Scholar 

  22. Idris AI, Rojas J, Greig IR, Van’t Hof RJ, Ralston SH (2008) Aminobisphosphonates cause osteoblast apoptosis and inhibit bone nodule formation in vitro. Calcif Tissue Int 82(3):191–201

    Article  CAS  PubMed  Google Scholar 

  23. Wu P, Koharski C, Nonnenmann H, Vashishth D (2003) Loading on non-enzymatically glycated and damaged bone results in an instantaneous fracture. Trans Orthop Res Soc 28:404

    Google Scholar 

  24. Gourion-Arsiquaud S, Faibish D, Myers E, Spevak L, Compston J, Hodsman A, Shane E, Recker RR, Boskey ER, Boskey AL (2009) Use of FTIR spectroscopic imaging to identify parameters associated with fragility fracture. J Bone Miner Res 24(9):1565–1571

    Article  PubMed Central  PubMed  Google Scholar 

  25. Wang X, Li X, Shen X, Agrawal CM (2003) Age-related changes of noncalcified collagen in human cortical bone. Ann Biomed Eng 31(11):1365–1371

    Article  PubMed  Google Scholar 

  26. Boivin G, Meunie PJ (2001) Changes in bone remodeling rate influence the degree of mineralization of bone which is a determinant of bone strength: therapeutic implications. Adv Exp Med Biol 496:123–127

    Article  CAS  PubMed  Google Scholar 

  27. Gourion-Arsiquaud S, Allen MR, Burr DB, Vashishth D, Tang SY, Boskey AL (2010) Bisphosphonate treatment modifies canine bone mineral and matrix properties and their heterogeneity. Bone 46(3):666–672

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  28. Boskey AL, Spevak L, Weinstein RS (2009) Spectroscopic markers of bone quality in alendronate-treated postmenopausal women. Osteoporos Int 20(5):793–800

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  29. Whyte MP (2009) Atypical femoral fractures, bisphosphonates, and adult hypophosphatasia. J Bone Miner Res 24(6):1132–1134

    Article  PubMed  Google Scholar 

  30. Rozin AP (2003) Is Methotrexate osteopathy a form of bone idiosyncrasy? Ann Rheum Dis 62:1123

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  31. Eriksen EF, Díez-Pérez A, Boonen S (2014) Update on long-term treatment with bisphosphonates for postmenopausal osteoporosis: a systematic review. Bone 58:126–135

    Article  CAS  PubMed  Google Scholar 

  32. Levis S, Theodore G (2012) Summary of AHRQ’s comparative effectiveness review of treatment to prevent fractures in men and women with low bone density or osteoporosis: update of the 2007 report. J Manag Care Pharm 18(4 Suppl B):S1–S15, discussion S13

    PubMed  Google Scholar 

  33. Neviaser AS, Lane JM, Lenart BA, Edobor-Osula F, Lorich DG (2008) Low-energy femoral shaft fractures associated with alendronate use. J Orthop Trauma 22(5):346–350

    Article  PubMed  Google Scholar 

  34. Schilcher J, Aspenberg P (2009) Incidence of stress fractures of the femoral shaft in women treated with bisphosphonate. Acta Orthop 80(4):413–415

    Article  PubMed Central  PubMed  Google Scholar 

  35. Black DM, Schwartz AV, Ensrud KE, Cauley JA, Levis S, Quandt SA et al (2006) Effects of continuing or stopping alendronate after 5 years of treatment: the Fracture Intervention Trial Long-term Extension (FLEX)—a randomized trial. JAMA 296:2927–2938

    Article  CAS  PubMed  Google Scholar 

  36. Bone HG, Hosking D, Devogelaer JP, Tucci JR, Emkey RD, Tonino RP et al (2004) Ten years’ experience with alendronate for osteoporosis in postmenopausal women. N Engl J Med 350:1189–1199

    Article  CAS  PubMed  Google Scholar 

  37. Tonino RP, Meunier PJ, Emkey R, Rodriguez-Portales JA, Menkes CJ, Wasnich RD et al (2000) Skeletal benefits of alendronate: 7-year treatment of postmenopausal osteoporotic women. Phase III Osteoporosis Treatment Study Group. J Clin Endocrinol Metab 85:3109–3115

    CAS  PubMed  Google Scholar 

  38. Shane E, Burr D, Ebeling PR, Abrahamsen B, Adler RA, Brown TD, Cheung AM, Cosman F, Curtis JR, Dell R, Dempster D, Einhorn TA, Genant HK, Geusens P, Klaushofer K, Koval K, Lane JM, McKiernan F, McKinney R, Ng A, Nieves J, O’Keefe R, Papapoulos S, Sen HT, van der Meulen MC, Weinstein RS, Whyte M (2010) American Society for Bone and Mineral Research. Atypical subtrochanteric and diaphyseal femoral fractures: report of a task force of the American Society for Bone and Mineral Research. J Bone Miner Res 25(11):2267–2294

    Article  PubMed  Google Scholar 

  39. Handoll HH, Pearce P. Interventions for treating isolated diaphyseal fractures of the ulna in adults. Cochrane Database Syst Rev. 2012 Jun 13;6:CD000523. doi:10.1002/14651858.CD000523.pub4

  40. Mackay D, Wood L, Rangan A (2000) The treatment of isolated ulnar fractures in adults: a systematic review. Injury 31(8):565–570

    Article  CAS  PubMed  Google Scholar 

  41. Saka G, Sağlam N, Kurtulmuş T, Özer C, Uğurlar M, Akpınar F (2013) Interlocking intramedullary ulna nails in isolated ulna diaphyseal fractures: a retrospective study. Acta Orthop Traumatol Turc 47(4):236–243

    Article  PubMed  Google Scholar 

  42. Saita Y, Ishijima M, Mogami A, Kubota M, Baba T, Kaketa T, Nagao M, Sakamoto Y, Sakai K, Kato R, Nagura N, Miyagawa K, Wada T, Liu L, Obayashi O, Shitoto K, Nozawa M, Kajihara H, Gen H, Kaneko K (2014) The fracture sites of atypical femoral fractures are associated with the weight-bearing lower limb alignment. Bone 66:105–110

    Article  PubMed  Google Scholar 

  43. Chen LP, Chang TK, Huang TY, Kwok TG, Lu YC (2014) The correlation between lateral bowing angle of the femur and the location of atypical femur fractures. Calcif Tissue Int 95(3):240–247. doi:10.1007/s00223-014-9887-y

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Tan, S.H.S., Saseendar, S., Tan, B.H.M. et al. Ulnar fractures with bisphosphonate therapy: a systematic review of published case reports. Osteoporos Int 26, 421–429 (2015). https://doi.org/10.1007/s00198-014-2885-0

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  • DOI: https://doi.org/10.1007/s00198-014-2885-0

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