ATYPICAL FRACTURES DUE TO LONG TREATMENT WITH BISPHOSPHONATES (CRITICAL REVIEW)

Cover Page


Cite item

Full Text

Abstract

This paper reviews the evidence for an association between atypical subtrochanteric fractures and long-term bisphosphonate use. A PubMed search of literature was performed. Estimation of scientific level of evidences, extraction of quantitative data about atypical fractures from publication were performed. Common clinical and X-ray features of ‘atypical’ fractures are described. Level IV publications contain assumptions of relationship between long term (more than 5 years) bisphosphonates’ (alendronate, ibandronate) treatment and atypical fractures. No data found about connection between zoledronic acid and atypical fractures. Data about relative risk of atypical fractures which is retrieved from meta-analysis’s and post-hock analysis’s of randomized clinical investigations is discrepant. No meta-analysis’s and randomized clinical investigations with statistically valid evidence of correlation between atypical fractures and long term bisphosphonates treatment have been found. Despite the relative rarity of atypical femoral fractures and doubtful evidences of their connection to bisphosphonates therapy, physicians and patients should be made aware of the possibility of such phenomenon. Principles of rational bisphosphonates therapy are being discussing. Because bisphosphonates accumulate in bone, they create a reservoir leading to continued release from bone for months or years after treatment is stopped. The feature described above is the base to recommendation for a drug holiday after 5-10 yr of bisphosphonate treatment. Clinical recommendations to reduce risks, rational diagnostic and surgical algorithm to treat atypical fractures are proposed for physicians dealing with osteoporosis, osteoporotic fractures and their consequences. Researches should be undertaken to get additional epidemiologic and clinical data to establish the true relationship between atypical fractures and long term bisphosphonates using. Bisphosphonates are effective and relatively safe remedies which reduce risk of osteoporotic fractures of any part of skeleton. Clinical advantages of bisphosphonates using exceed the doubtful and unproved risk of atypical fractures.

About the authors

G. S. Golubev

Rostov State Medical University

Author for correspondence.
Email: ortho-rostgmu@yandex.ru
Russian Federation

References

  1. Abrahamsen B., Eiken P., Eastell R. Cumulative alendronate dose and the long-term absolute risk of subtrochanteric and diaphyseal femur fractures: a register-based national cohort analysis. J. Clin. Endocrinol. Metab. 2010; 95 (12):5258-5265.
  2. 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; (6):1095-1102.
  3. Banffy M.B., Vrahas M.S., Ready J.E., Abraham J.A. Nonoperative versus prophylactic treatment of bisphosphonate-associated femoral stress fractures. Clin. Orthop. Relat. Res. 2011; 469 (7):2028-2034.
  4. Bauss F., Lalla S., Endele R., Hothorn L.A. Effects of treatment with ibandronate on bone mass, architecture, biomechanical properties, and bone concentration of ibandronate in ovariectomized aged rats. J. Rheumatol. 2002; 29 (10):2200-2208.
  5. Bauss F., Russell R.G. Ibandronate in osteoporosis: preclinical data and rationale for intermittent dosing. Osteoporos Int. 2004; 15 (6):423-433.
  6. Black D.M., Bauer D.C., Schwartz A.V., Cummings S.R., Rosen C.J. Continuing bisphosphonate treatment for osteoporosis - for whom and for how long? N. Engl. J. Med. 2012; 366 (22):2051-2053.
  7. Black D.M., Delmas P.D., Eastell R., Reid I.R., Boonen S., Cauley J.A., Cosman F., Lakatos P., Leung P.C., Man Z., Mautalen C., Mesenbrink P., Hu H., Caminis J., Tong K., Rosario-Jansen T., Krasnow J., Hue T.F., Sellmeyer D. Once-yearly zoledronic acid for treatment of postmenopausal osteoporosis. N. Engl. J. Med. 2007; 356 (18):1809-1822.
  8. Black D.M., Kelly M.P., Genant H.K., Palermo L., Eastell R., Bucci-Rechtweg C., Cauley J., Leung P.C., Boonen S., Santora A., de Papp A., Bauer D.C., CN -FITSCC -HPF. Bisphosphonates and fractures of the subtrochanteric or diaphyseal femur. N. Engl. J. Med. 2010; 362 (19):1761-1771.
  9. Black D.M., Schwartz A.V., Ensrud K.E., Cauley J.A., Levis S., Quandt S.A., Satterfield S., Wallace R.B., Bauer D.C., Palermo L., Wehren L.E., Lombardi A., Santora A.C., Cummings S.R., CN - FRG. 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 (24):2927-2938.
  10. Capeci C.M., Tejwani N.C. Bilateral low-energy simultaneous or sequential femoral fractures in patients on long-term alendronate therapy. J. Bone Joint Surg. Am. 2009; 91 (11):2556-2561.
  11. Carvalho N.N., Voss L.A., Almeida M.O., Salgado C.L., Bandeira F. Atypical femoral fractures during prolonged use of bisphosphonates: short-term responses to strontium ranelate and teriparatide. J. Clin. Endocrinol. Metab. 2011; 96 (9):2675-2680.
  12. Cauley J.A., Black D., Boonen S., Cummings S.R., Mesenbrink P., Palermo L., Man Z., Hadji P., Reid I.R., CN - HPFG. Once-yearly zoledronic acid and days of disability, bed rest, and back pain: randomized, controlled HORIZON Pivotal Fracture Trial. J. Bone Miner. Res. 2011; 26 (5):984-992.
  13. Chan S.S., Rosenberg Z.S., Chan K., Capeci C. Subtrochanteric femoral fractures in patients receiving long-term alendronate therapy: imaging features. Am. J. Roentgenol. 2010; 194 (6):1581-1586.
  14. Cooper C. Beyond daily dosing: clinical experience. Bone. 2006; 38 (4) Suppl. 1):S13-17.
  15. Cremers S., Papapoulos S. Pharmacology of bisphosphonates. Bone. 2011; 49 (1):42-49.
  16. Cummings S.R., Black D.M., Thompson D.E., Applegate W.B., Barrett-Connor E., Musliner T.A., Palermo L., Prineas R., Rubin S.M., Scott J.C., Vogt T., Wallace R., Yates A.J., LaCroix A.Z. 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 (24):2077-2082.
  17. David M., Reid J.D., Saag K., Roux Ch., Lau Ch.-S., Reginster J.-Y., Papanastasiou P., Ferreira A., Hartl F., TaiwoFashola, Mesenbrink P., Sambrook P.N. Zoledronic acid and risedronate in the prevention and treatment of glucocorticoid-induced osteoporosis (HORIZON): a multicentre, double-blind, double-dummy, randomised controlled trial. Lancet. 2009; 373:1253-1263.
  18. FDA Background document for meeting of advisory committee for reproductive health drugs and drug safety and risk management advisory committee 2011. N 22.07.2012. P. 1-182.
  19. FDA Drug Safety Communication: Safety update for osteoporosis drugs, bisphosphonates, and atypical fractures, 10.13.2010. Режим доступа: http://www.fda. gov/Drugs/DrugSafety/ucm229009.htm (дата обращения 29.07.2012).
  20. Ferretti J.L. Effects of bisphosphonates on bone biomechanics Chapter 31. In: Bijvoet O., Fleisch H.A., Canfield R.E., Russell R.G.G., eds. Bisphosphonatesonbone. Amsterdam: ElsevierScience B.V., 1995. 337 p.
  21. Flora L, Hassing GS, Cloyd GG, Bevan JA, Parfitt AM, Villanueva AR. The long-term skeletal effects of EHDP in dogs. Metab. Bone Dis. Relat. Res. 1981; 3 (4-5):289-300.
  22. Fowler J.R., Criner K., Craig M.R. Prophylactic intramedullary fixation for bisphosphonate-related subtrochanteric stress fracture. Orthopedics. 2012; 35 (6):e954-957 LID - 10.3928/0147.
  23. Grady M.K., Watson J.T., Cannada L.K. Treatment of femoral fracture nonunion after long-term bisphosphonate use. Orthopedics. 2012; 35 (6):e991-995 LID - 10.3928/0147.
  24. Ha Y.C., Cho M.R., Park K.H., Kim S.Y., Koo K.H. Is surgery necessary for femoral insufficiency fractures after long-term bisphosphonate therapy? Clin. Orthop. Relat. Res. 2010; 468 (12):3393-3398.
  25. Hofbauer L.C., Jakob F., Felsenberg D. Bisphosphonates and atypical femoral fractures. N. Engl. J. Med. 2010; 363 (11):1084; authorreply 1-5.
  26. Holick M.F., Binkley N.C., Bischoff-Ferrari H.A., Gordon C.M., Hanley D.A., Heaney R.P., Murad M.H., Weaver C.M., CN - ES. Evaluation, treatment, and prevention of vitamin D deficiency: an Endocrine Society clinical practice guideline. J. Clin. Endocrinol. Metab. 2011; 96 (7):1911-1930.
  27. Janner M., Muhlbauer R.C., Fleisch H. Sodium EDTA enhances intestinal absorption of two bisphosphonates. Calcif. Tissue Int. 1991; 49 (4):280-3.
  28. Lee J., Vasikaran S. Current recommendations for laboratory testing and use of bone turnover markers in management of osteoporosis. Ann. Lab. Med. 2012; 32 (2):105-112.
  29. Lim C.T., Setiobudi T., Das De S. Femoral canal obliteration secondary to prolonged alendronate use: a case report. J. Orthop. Surg. (Hong Kong) 2012; 20 (1):115-117.
  30. Mashiba T., Mori S., Burr D.B., 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.
  31. Mellstrom D.D., Sorensen O.H., Goemaere S., Roux C., Johnson T.D., Chines A.A. Seven years of treatment with risedronate in women with postmenopausal osteoporosis. Calcif. Tissue Int. 2004; 75 (6):462-468.
  32. Nieves J.W., Cosman F. Atypical subtrochanteric and femoral shaft fractures and possible association with bisphosphonates. Curr. Osteoporos Rep. 2010; 8 (1):34-39.
  33. OCEBM Levels of evidence working group. "The Oxford 2011 levels of evidence". Oxford Centre for Evidence-Based Medicine. Режим доступа: http:// www.cebm.net/index.aspx?o = 5653 (дата обращения 26.04.2012).
  34. Odvina C.V., Zerwekh J.E., Rao D.S., Maalouf N., Gottschalk F.A., Pak C.Y. Severely suppressed bone turnover: a potential complication of alendronate therapy. J. Clin. Endocrinol. Metab. 2005; 90 (3):1294-1301.
  35. Osteoporosis drug market- global and China market analysis, size, trends and forecast (2010-2015). Режим доступа: http://www.transparencymarketresearch. com/osteoporosis-drug-market.html (дата обращения 28.04.2012).
  36. Oxford centre for evidence-based medicine - levels of evidence (March 2009). URL: http://www.cebm.net/ index.aspx?o=1025 (дата обращения 26.04.2012).
  37. Reddy S.V., Gupta S.K. Atypical femoral shaft fracture in a patient with non-metastatic prostate cancer on zoledronic acid therapy: effect of therapy or coincidence? Singapore Med. J. 2012; 53 (3):e52-54.
  38. Reitsma P.H., Bijvoet O.L., Verlinden-Ooms H., van der WeL. Kinetic studies of bone and mineral metabolism during treatment with (3-amino-1-hydroxypropylidene)-1,1-bisphosphonate (APD) in rats. Calcif. Tissue Int. 1980; 32 (2):145-157.
  39. Rizzoli R., Akesson K., Bouxsein M., Kanis J.A., Napoli N., Papapoulos S., Reginster J.Y., Cooper C. Subtrochanteric fractures after long-term 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 (2):373-390.
  40. Schilcher J., Aspenberg P. Incidence of stress fractures of the femoral shaft in women treated with bisphosphonate. Acta Orthop. 2009; 80 (4):413-415.
  41. Sebba A. Osteoporosis: how long should we treat? Curr. Opin. Endocrinol. Diabetes Obes. 2008; 15 (6):502-507.
  42. Sellmeyer D.E. Atypical fractures as a potential complication of long-term bisphosphonate therapy. JAMA. 2010; 304 (13):1480-1484.
  43. Shane E., Burr D., Ebeling P.R., Abrahamsen B., Adler R.A., Brown T.D., Cheung A.M., Cosman F., Curtis J.R., Dell R., Dempster D., Einhorn T.A., Genant H.K., Geusens P., Klaushofer K., Koval K., Lane J.M., McKiernan F. Atypical subtrochanteric and diaphyseal femoral fractures: report of a task force of the American Society for Bone and Mineral Research. J. Bone Miner. Res. 2010; 25 (11):2267-2294.
  44. Silverman S.L., Ott S.M., Dell R.M. Bisphosphonates and atypical femoral fractures. N. Engl. J. Med. 2010; 363 (11):1083; authorreply 1-5.
  45. Somford M.P., Geurts G.F., den Teuling J.W., Thomassen B.J., Draijer W.F. Long-term alendronate use not without consequences? Int. J. Rheumatol. 2009; 2009:253432.
  46. Stakkestad J.A., Lakatos P., Lorenc R., Sedarati F., Neate C., Reginster J.Y. Monthly oral ibandronate is effective and well tolerated after 3 years: the MOBILE long-term extension. Clin. Rheumatol. 2008; 27 (8):955-960.
  47. Thompson R.N., Phillips J.R., McCauley S.H., Elliott J.R., Moran C.G. Atypical femoral fractures and bisphosphonate treatment: experience in two large United Kingdom teaching hospitals. J. Bone Joint Surg. Br. 2012; 94 (3):385-390.
  48. US Osteoporosis Market. Режим доступа: http:// www.researchandmarkets.com/reports/612778/ us_osteoporosis_market.pdf (дата обращения 28.04.2012).
  49. Visekruna M., Wilson D., McKiernan F.E. Severely suppressed bone turnover and atypical skeletal fragility. J. Clin. Endocrinol. Metab. 2008; 93 (8):2948-2952.
  50. Wang K., Moaveni A., Dowrick A., Liew S. Alendronate-associated femoral insufficiency fractures and femoral stress reactions. J. Orthop. Surg. (HongKong) 2011; 19(1):89-92.
  51. Watts N.B., Chines A., Olszynski W.P., McKeever C.D., McClung M.R., Zhou X., Grauer A. Fracture risk remains reduced one year after discontinuation of risedronate. Osteoporos Int. 2008; 19 (3): 365-372.
  52. Watts N.B., Diab D.L. Long-term use of bisphosphonates in osteoporosis. J. Clin. Endocrinol. Metab. 2010; 95 (4):1555-1565.
  53. Weil Y.A., Rivkin G., Safran O., Liebergall M., Foldes A.J. The outcome of surgically treated femur fractures associated with long-term bisphosphonate use. J. Trauma 2011; 71 (1):186-190.
  54. Yoon R.S., Beebe K.S., Benevenia J. Prophylactic bilateral intramedullary femoral nails for bisphosphonate-associated signs of impending subtrochanteric hip fracture. Orthopedics. 2010. Apr. 16:267-270. doi: 10.3928/01477447-20100225-21 (режим доступа: http://www.ncbi.nlm.nih.gov/pubmed).

Supplementary files

Supplementary Files
Action
1. JATS XML
Download

Copyright (c)


СМИ зарегистрировано Федеральной службой по надзору в сфере связи, информационных технологий и массовых коммуникаций (Роскомнадзор).
Регистрационный номер и дата принятия решения о регистрации СМИ: серия ПИ № ФС 77 - 82474 от 10.12.2021.


This website uses cookies

You consent to our cookies if you continue to use our website.

About Cookies