Skeletal Radiology

, Volume 41, Issue 7, pp 861–865 | Cite as

Osteoclast abnormalities in fractured bone during bisphosphonate treatment for osteoporosis: a case report

  • V. J. V. Vigorita
  • J. S. Silver
  • E. O. E. Eisemon
Case Report

Abstract

Bisphosphonates have been widely used in the treatment of an array of bone disorders. Recent complications have included unusual femoral fractures in patients who have received long term bisphosphonate treatment for osteoporosis. Although it has been shown that bisphosphonates are effective by blunting osteoclast resorption, there has been little morphologic description of the local tissue activity at the site of these unusual fractures. To evaluate for local changes to bone morphology at the fracture site in patients presenting with a bisphosphonate-related femur fracture, a sample of cortical bone was obtained at the site of a bisphosphonate fracture and was processed in a nondecalcified manner. The specimen was evaluated for potential cellular changes consistent with bisphosphonate treatment. Significant osteoclast abnormalities at the fracture site were found in a 69-year-old woman treated for 2 years with Fosamax substantiating that bone remodeling at this site is distinctly abnormal. Addressing the osteoclast dysfunction should be a focus of future therapeutic attention and intervention.

Keywords

Bisphosphonates Metabolic bone disease Osteoporosis 

References

  1. 1.
    Favus MJ. Bisphosphonates for osteoporosis. N Engl J Med. 2010;363(21):2027–35.PubMedCrossRefGoogle Scholar
  2. 2.
    Rosen CJ. Vitamin D insufficiency. N Engl J Med. 2011;364:248–53.Google Scholar
  3. 3.
    Bogunovic L, Kim AD, Beamer BS, Nguyen J, Lane JM. Hypovitaminosis D in patients scheduled to undergo orthopaedic surgery. A single center analysis. J Bone Joint Surg Br. 2010;92(13):2300–4.CrossRefGoogle Scholar
  4. 4.
    Stewler G. Decimal point osteoporosis at the 10 year mark. N Engl J Med. 2004;350(12):1172–4.CrossRefGoogle Scholar
  5. 5.
    Russell RG. Bisphosphonates: an update on mechanisms of action and how these relate to clinical efficacy. Ann NY Acad Med. 2007;1117:209–57.CrossRefGoogle Scholar
  6. 6.
    Scwartz Z. Osteoconductivity of demineralized bone matrix is independent of donor bisphosphonateuse. J Bone Jt Surg. 2011;93(24):2278–86.CrossRefGoogle Scholar
  7. 7.
    Shane E, Burr D, Ebeling PR, Abrahamsen B, Adler RA, Brown TD, et al. Atypical subtrochanteric and diaphyseal femoral fractures: report of a task force of the American Society of Bone and Mineral Rresearch. J Bone Miner Res. 2010;25(11):2267–94.PubMedCrossRefGoogle Scholar
  8. 8.
    Allen MR, Ginetys E, Leeming DJ, Burr DB, Delmas PD. Bisphosphonates alter trabecular bone collagen cross-linking and isomerization in beagle dog vertebra. Osteoporosis Intl. 2008;19(3):329–37.CrossRefGoogle Scholar
  9. 9.
    Allen MR, Iwata K, Phipps R, Burr DB. Alterations in canine vertebral bone turnover, microdamge accumulation, and biochemical properties following 1 year treatment with clinical treatment doses of risedronate or alendronate. Bone. 2006;39(4):872–9.PubMedCrossRefGoogle Scholar
  10. 10.
    Iwata K, Allen MR, Phipps R, Burr DB. Microcrack initiation occurs more easily in vertebrae from beagles treated with alendronate than risedronate. Bone. 2006;38(Suppl):42.CrossRefGoogle Scholar
  11. 11.
    Allen MR, Reinwald S, Burr DB. Alendronate reduces bone toughness of ribs without significantly increasing microdamage accumulation in dogs following 3 years of daily treatment. Calcif Tissue Intl. 2008;82(5):354–60.CrossRefGoogle Scholar
  12. 12.
    Forwood MR, Burr DB, Takano Y, Eastman DF, Smith PN, Schwartz JD. Risedronate does not increase microdamage in the canine femoral neck. Bone. 1995;16(6):643–50.PubMedCrossRefGoogle Scholar
  13. 13.
    Li J, Miller MA, Hutchins GD, Burr DB. Imaging bone microdamage in vivo with positive positron emission tomography. Bone. 2005;37(6):819–24.PubMedCrossRefGoogle Scholar
  14. 14.
    Mashiba T, Turner CH, Hirano T, Forwood MR, Johnston CC, Burr D. Effects of suppressed bone turnover by bisphosphonates on microdamage accumulation and biochemical properties in clinically relevant skeletal sites in beagles. Bone. 2001;28(5):524–31.PubMedCrossRefGoogle Scholar
  15. 15.
    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(4):613–20.PubMedCrossRefGoogle Scholar
  16. 16.
    Fournier P, Boissier S, Filleur S, Guglielmi J, Cabon F, Colombel M, Clezardin P. Bisphosphonates inhibit angiogenesis in vitro and testosterone -stimulated vascular regrowth in the ventral prostate in castrated rats. Cancer Res. 2002;62(22):6538–44.PubMedGoogle Scholar
  17. 17.
    Hughes D. Bisphosphonates promote apoptosis in murine osteoclasts in vitro and in vivo. J Bone Miner Res. 1995;10(10):1478–87.PubMedCrossRefGoogle Scholar
  18. 18.
    Coxon H. Protein geranylgeranylation is required for osteoclast formation, function and survival: inhibition by bisphosphonates and GGGTI-298. J Bone Miner Res. 2000;15(8):1467–76.PubMedCrossRefGoogle Scholar
  19. 19.
    Mautalen C, Gonzales D, Blumenfeld EL, Araujo ES, Schajowicz F. Spontaneous fractures of uninvolved bones in patients with Paget’s disease during unduly prolonged with disodium etidronate (EHDP). Clin Orthop Related Res. 1986;207:150–5.Google Scholar
  20. 20.
    Al Muderis A, Azzopardi T, Cundy P. Zebra lines of pamidronate therapy in children. J Bone Joint Surg. 2007;89:1511–6.Google Scholar
  21. 21.
    Armamento-Villareal R, Napoli N, Panwar V, Novack D. Suppressed bone turnover during alendronate therapy for high-turnover osteoporosis. N Engl J Med. 2006;355:2048–50.Google Scholar
  22. 22.
    Dodson TB, Raje NS, Caruso PA, Rosenberg AE. Case 9-2008: a 65 year old woman with a non-healing ulcer of the jaw. N Engl J Med. 2008;358:1283–91.Google Scholar
  23. 23.
    Woo S, Hande K, Richardson PG. Letter to the editor. N Engl J Med. 2005;353:100.Google Scholar
  24. 24.
    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(11):2556–61.PubMedCrossRefGoogle Scholar
  25. 25.
    De Das S, Setiobudi T, Shen L. A rational approach to management of alendronate-related subtrochanteric fractures. J Bone Joint Surg Br. 2010;92(5):679–86.CrossRefGoogle Scholar
  26. 26.
    Isaacs JD, Shidiak L, Harris IA, Szomor ZL. Femoral insufficiency fractures associated with prolonged bisphosphonate therapy. Clin Orthop Relat Res. 2010;468:3384–92.PubMedCrossRefGoogle Scholar
  27. 27.
    Lenart B, Neviaser A, Lyman S, Chang C, Edobor-Osula F, Steele B, et al. Association of low-energy femoral fractures with prolonged bisphosphonate use: a case control study. Osteoporos Int. 2009;20(8):1353–62.PubMedCrossRefGoogle Scholar
  28. 28.
    Odvina CV, Levy S, Rao S, Zerwekh JE, Rao DS. Unusual mid-shaft fractures during long-term bisphosphonate therapy. Clin Endocrinol. 2010;72(2):161–8.CrossRefGoogle Scholar
  29. 29.
    Sayed-Noor AS, Sjoden G. Two femoral insufficiency fractures after long term alendronate therapy. Clin Orthop Relat Res. 2009;467:1921–6.PubMedCrossRefGoogle Scholar
  30. 30.
    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(6):1095–102.PubMedCrossRefGoogle Scholar
  31. 31.
    Giusti A, Hamdy NAT, Papapoulus SE. Atypical fractures of the femur and bisphosphonate therapy. A systemic review of case/case series studies. Bone. 2010;47:169–80.Google Scholar
  32. 32.
    Black DM, Kelly M, Genant HK, Palermo L, Eastell R, Bucci-rechteg C, et al. Bisphosphonates and fractures of the subtrochanteric or diaphyseal femur. N Engl J Med. 2010;362(19):1761–71.PubMedCrossRefGoogle Scholar
  33. 33.
    Somford M, Draijer F, Thomassen BJW, Chavassieux PM, Boivin G, Papapoulos SE. Bilateral fractures of the femur diaphysis in a patient with rheumatoid arthritis on long–term treatment with alendronate: clues to the mechanism of increased. J Bone Miner Res. 2009;24(10):1736–40.PubMedCrossRefGoogle Scholar
  34. 34.
    Weinstein RS, Roberson PK, Manolagas SC. Giant osteoclast formation and long term oral bisphosphonate therapy. N Engl J Med. 2009 ;360:53–62. Google Scholar

Copyright information

© ISS 2012

Authors and Affiliations

  • V. J. V. Vigorita
    • 1
  • J. S. Silver
    • 1
  • E. O. E. Eisemon
    • 1
  1. 1.Maimonides Medical CenterBrooklynUSA

Personalised recommendations