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Calcified Tissue International

, Volume 104, Issue 3, pp 313–319 | Cite as

Bisphosphonates Use and Risk of Subtrochanteric and Diaphyseal Femur Fractures in Korea: Results from the National Claim Registry

  • Young-Kyun Lee
  • Dong Won ByunEmail author
  • Sung-Mok Jung
  • Hye-Young Kwon
  • Ha-Young Kim
  • Se Hwa Kim
  • Tae-Young KimEmail author
  • Sunmee Jang
  • Yong-Chan Ha
Original Research
  • 132 Downloads

Abstract

Although Asian with bisphosphonate has been considered to have higher risk of subtrochanteric and diaphyseal femur (ST/DF) fractures, the occurrence of those fractures has been still unclear in Asia. The purpose of this study was to investigate the incidence rate of ST/DF fractures among bisphosphonate users from nationwide database in South Korea. Using national health insurance claim database, we only included the bisphosphonate users who took bisphosphonate for the first time in 2008 and evaluated the incidence rate of ST/DF fracture from 2008 to 2013. Non-user controls were matched to bisphosphonate users by propensity score matching with age and gender. Cox regression models were used to calculate hazard ratios of ST/DF fracture with and without adjustment for comorbidity. A total of 682 ST/DF fractures were observed among 348,311 bisphosphonate users. The incidence rate of ST/DF fracture among bisphosphonate users (37.75/100,000 person years, 95% CI 35.02–40.70) was higher compared with non-users (24.41/100,000 person years, 95% CI 22.31–26.71). The risk of ST/DF fracture was greater in bisphosphonate users compared with non-users (hazard ratio 1.541, 1.370–1.734; p < 0.001). The incidence rate of ST/DF fracture after bisphosphonate use could be determined in Korean patients, which can provide basal information for further studies on risk and benefit of continuing bisphosphonate.

Keywords

Bisphosphonates Atypical femur fracture Incidence rate Korea 

Notes

Acknowledgements

This research was supported by a grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Korea (Grant Number: HI13C1522).

Author Contributions

Y-KL, DWB, H-YK, H-YK, SHK, T-YK, SJ, and Y-CH designed the study. Y-KL, DWB, S-MJ, H-YK, H-YK, SHK, T-YK, and SJ contributed to the acquisition, analysis, or interpretation of data. Y-KL, DWB, S-MJ, H-YK, H-YK, T-YK, and Y-CH prepared the first draft of the manuscript. Y-KL, DWB, S-MJ, H-YK, H-YK, SHK, T-YK, SJ, and Y-CH contributed to the critical revision of the manuscript for important intellectual content. Y-KL, DWB, S-MJ, H-YK, H-YK, SHK, SJ, and Y-CH were responsible for statistical analysis of the data. Y-KL, S-MJ, H-YK, SHK, T-YK, SJ, and Y-CH contributed to the administrative, technical, or material support. All authors revised the paper critically for intellectual content and approved the final version. All authors agree to be accountable for the work and to ensure that any questions relating to the accuracy and integrity of the paper are investigated and properly resolved.

Compliance with Ethical Standards

Conflict of interest

Young-Kyun Lee, Dong Won Byun, Sung-Mok Jung, Hye-Young Kwon, Ha-Young Kim, Se Hwa Kim, Tae-Young Kim, Sunmee Jang, and Yong-Chan Ha declare that they have no conflict of interest.

Research Involving Human Participants

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed Consent

Patient consent was not obtained because patient records/information were anonymized and de-identified prior to analysis.

References

  1. 1.
    Ethgen O, Tellier V, Sedrine WB, De Maeseneer J, Gosset C, Reginster JY (2003) Health-related quality of life and cost of ambulatory care in osteoporosis: how may such outcome measures be valuable information to health decision makers and payers? Bone 32:718–724CrossRefPubMedGoogle Scholar
  2. 2.
    Johnell O, Kanis JA (2006) An estimate of the worldwide prevalence and disability associated with osteoporotic fractures. Osteoporos Int 17:1726–1733CrossRefPubMedGoogle Scholar
  3. 3.
    Kanis JA (2002) Diagnosis of osteoporosis and assessment of fracture risk. Lancet 359:1929–1936CrossRefPubMedGoogle Scholar
  4. 4.
    Cheung AM, Detsky AS (2008) Osteoporosis and fractures: missing the bridge? JAMA 299:1468–1470CrossRefPubMedGoogle Scholar
  5. 5.
    Schousboe JT, Taylor BC, Fink HA, Kane RL, Cummings SR, Orwoll ES, Melton LJ 3rd, Bauer DC, Ensrud KE (2007) Cost-effectiveness of bone densitometry followed by treatment of osteoporosis in older men. JAMA 298:629–637CrossRefPubMedGoogle Scholar
  6. 6.
    Elliot-Gibson V, Bogoch ER, Jamal SA, Beaton DE (2004) Practice patterns in the diagnosis and treatment of osteoporosis after a fragility fracture: a systematic review. Osteoporos Int 15:767–778CrossRefPubMedGoogle Scholar
  7. 7.
    Papapoulos SE, Quandt SA, Liberman UA, Hochberg MC, Thompson DE (2005) Meta-analysis of the efficacy of alendronate for the prevention of hip fractures in postmenopausal women. Osteoporos Int 16:468–474CrossRefPubMedGoogle Scholar
  8. 8.
    Miller PD (2001) Bisphosphonates for the prevention and treatment of corticosteroid-induced osteoporosis. Osteoporos Int 12(Suppl 3):S3–S10CrossRefPubMedGoogle Scholar
  9. 9.
    Sorensen OH, Storm T, Thamsborg G, Sorensen HA, Kollerup G, Steiniche T, Melsen F, Genant HK (1993) Bisphosphonates and osteoporosis. Osteoporos Int 3(Suppl 1):223–225CrossRefPubMedGoogle Scholar
  10. 10.
    Colon-Emeric CS (2006) Ten vs five years of bisphosphonate treatment for postmenopausal osteoporosis: enough of a good thing. JAMA 296:2968–2969CrossRefPubMedGoogle Scholar
  11. 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 29:1–23CrossRefPubMedGoogle Scholar
  12. 12.
    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, Mineral R (2010) American Society for B. Atypical subtrochanteric and diaphyseal femoral fractures: report of a task force of the American Society for Bone and Mineral Research. J Bone Miner Res 25:2267–2294CrossRefPubMedGoogle Scholar
  13. 13.
    Koh A, Guerado E, Giannoudis PV (2017) Atypical femoral fractures related to bisphosphonate treatment: issues and controversies related to their surgical management. Bone Joint J 99-B:295–302CrossRefPubMedGoogle Scholar
  14. 14.
    Dell RM, Adams AL, Greene DF, Funahashi TT, Silverman SL, Eisemon EO, Zhou H, Burchette RJ, Ott SM (2012) Incidence of atypical nontraumatic diaphyseal fractures of the femur. J Bone Miner Res 27:2544–2550CrossRefPubMedGoogle Scholar
  15. 15.
    Schilcher J, Koeppen V, Aspenberg P, Michaelsson K (2014) Risk of atypical femoral fracture during and after bisphosphonate use. N Engl J Med 371:974–976CrossRefPubMedGoogle Scholar
  16. 16.
    Sellmeyer DE (2010) Atypical fractures as a potential complication of long-term bisphosphonate therapy. JAMA 304:1480–1484CrossRefPubMedGoogle Scholar
  17. 17.
    Teo BJ, Koh JS, Goh SK, Png MA, Chua DT, Howe TS (2014) Post-operative outcomes of atypical femoral subtrochanteric fracture in patients on bisphosphonate therapy. Bone Joint J 96-B:658–664CrossRefPubMedGoogle Scholar
  18. 18.
    Prasarn ML, Ahn J, Helfet DL, Lane JM, Lorich DG (2012) Bisphosphonate-associated femur fractures have high complication rates with operative fixation. Clin Orthop Relat Res 470:2295–2301CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    Schilcher J (2015) High revision rate but good healing capacity of atypical femoral fractures. A comparison with common shaft fractures. Injury 46:2468–2473CrossRefPubMedGoogle Scholar
  20. 20.
    Wang Z, Ward MM, Chan L, Bhattacharyya T (2014) Adherence to oral bisphosphonates and the risk of subtrochanteric and femoral shaft fractures among female medicare beneficiaries. Osteoporos Int 25:2109–2116CrossRefPubMedPubMedCentralGoogle Scholar
  21. 21.
    Kim SY, Schneeweiss S, Katz JN, Levin R, Solomon DH (2011) Oral bisphosphonates and risk of subtrochanteric or diaphyseal femur fractures in a population-based cohort. J Bone Miner Res 26:993–1001CrossRefPubMedGoogle Scholar
  22. 22.
    Hsiao FY, Huang WF, Chen YM, Wen YW, Kao YH, Chen LK, Tsai YW (2011) Hip and subtrochanteric or diaphyseal femoral fractures in alendronate users: a 10-year, nationwide retrospective cohort study in Taiwanese women. Clin Ther 33:1659–1667CrossRefPubMedGoogle Scholar
  23. 23.
    Abrahamsen B, Eiken P, Eastell R (2009) Subtrochanteric and diaphyseal femur fractures in patients treated with alendronate: a register-based national cohort study. J Bone Miner Res 24:1095–1102CrossRefPubMedGoogle Scholar
  24. 24.
    Nieves JW, Bilezikian JP, Lane JM, Einhorn TA, Wang Y, Steinbuch M, Cosman F (2010) Fragility fractures of the hip and femur: incidence and patient characteristics. Osteoporos Int 21:399–408CrossRefPubMedGoogle Scholar
  25. 25.
    Ha YC, Kim TY, Lee A, Lee YK, Kim HY, Kim JH, Park CM, Jang S (2016) Current trends and future projections of hip fracture in South Korea using nationwide claims data. Osteoporos Int 27:2603–2609CrossRefPubMedGoogle Scholar
  26. 26.
    Kim TY, Jang S, Park CM, Lee A, Lee YK, Kim HY, Cho EH, Ha YC (2016) Trends of incidence, mortality, and future projection of spinal fractures in Korea using nationwide claims data. J Korean Med Sci 31:801–805CrossRefPubMedPubMedCentralGoogle Scholar
  27. 27.
    Choi HJ, Shin CS, Ha YC, Jang SM, Jang SH, Park CM, Yoon HK, Lee SS (2011) Burden of osteoporosis in adults in Korea: a national health insurance database study. J Bone Miner Metab 30:54–58CrossRefPubMedGoogle Scholar
  28. 28.
    Lee YK, Ha YC, Choi HJ, Jang S, Park C, Lim YT, Shin CS (2013) Bisphosphonate use and subsequent hip fracture in South Korea. Osteoporos Int 24:2887–2892CrossRefPubMedGoogle Scholar
  29. 29.
    Ha YC, Lee YK, Lim YT, Jang SM, Shin CS (2014) Physicians’ attitudes to contemporary issues on osteoporosis management in Korea. J Bone Metab 21:143–149CrossRefPubMedPubMedCentralGoogle Scholar
  30. 30.
    Lee YK, Jang S, Ha YC (2015) Management of osteoporosis in South Korea. Crit Rev Eukaryot Gene Expr 25:33–40CrossRefPubMedGoogle Scholar
  31. 31.
    Lee YK, Ha YC, Park C, Yoo JJ, Shin CS, Koo KH (2013) Bisphosphonate use and increased incidence of subtrochanteric fracture in South Korea: results from the national claim registry. Osteoporos Int 24:707–711CrossRefPubMedGoogle Scholar
  32. 32.
    Giusti A, Hamdy NA, Papapoulos SE (2010) Atypical fractures of the femur and bisphosphonate therapy: a systematic review of case/case series studies. Bone 47:169–180CrossRefPubMedGoogle Scholar
  33. 33.
    Lo JC, Huang SY, Lee GA, Khandewal S, Provus J, Ettinger B, Gonzalez JR, Hui RL, Grimsrud CD (2012) Clinical correlates of atypical femoral fracture. Bone 51:181–184CrossRefPubMedGoogle Scholar
  34. 34.
    Marcano A, Taormina D, Egol KA, Peck V, Tejwani NC (2014) Are race and sex associated with the occurrence of atypical femoral fractures? Clin Orthop Relat Res 472:1020–1027CrossRefPubMedGoogle Scholar
  35. 35.
    Soh HH, Chua IT, Kwek EB (2015) Atypical fractures of the femur: effect of anterolateral bowing of the femur on fracture location. Arch Orthop Trauma Surg 135:1485–1490CrossRefPubMedGoogle Scholar
  36. 36.
    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 95:240–247CrossRefPubMedGoogle Scholar
  37. 37.
    Hagen JE, Miller AN, Ott SM, Gardner M, Morshed S, Jeray K, Alton TB, Ren D, Abblitt WP, Krieg JC (2014) Association of atypical femoral fractures with bisphosphonate use by patients with varus hip geometry. J Bone Joint Surg 96:1905–1909CrossRefPubMedGoogle Scholar
  38. 38.
    Schilcher J, Aspenberg P (2009) Incidence of stress fractures of the femoral shaft in women treated with bisphosphonate. Acta Orthop 80:413–415CrossRefPubMedPubMedCentralGoogle Scholar
  39. 39.
    Tamminen IS, Yli-Kyyny T, Isaksson H, Turunen MJ, Tong X, Jurvelin JS, Kroger H (2013) Incidence and bone biopsy findings of atypical femoral fractures. J Bone Miner Metab 31:585–594CrossRefPubMedGoogle Scholar
  40. 40.
    Meling T, Nawab A, Harboe K, Fosse L (2014) Atypical femoral fractures in elderly women: a fracture registry-based cohort study. Bone Joint J 96-B:1035–1040CrossRefPubMedGoogle Scholar
  41. 41.
    Kwon S (2003) Payment system reform for health care providers in Korea. Health Policy Plan 18:84–92CrossRefPubMedGoogle Scholar
  42. 42.
    Park BJ, Sung JH, Park KD, Seo SW, Kim S (2003) Report of the evaluation for validity of discharged diagnoses in Korean health insurance database. Seoul National University, SeoulGoogle Scholar
  43. 43.
    Charlson ME, Pompei P, Ales KL, MacKenzie CR (1987) A new method of classifying prognostic comorbidity in longitudinal studies: development and validation. J Chronic Dis 40:373–383CrossRefPubMedGoogle Scholar
  44. 44.
    Park-Wyllie LY, Mamdani MM, Juurlink DN, Hawker GA, Gunraj N, Austin PC, Whelan DB, Weiler PJ, Laupacis A (2011) Bisphosphonate use and the risk of subtrochanteric or femoral shaft fractures in older women. JAMA 305:783–789CrossRefPubMedGoogle Scholar
  45. 45.
    Schilcher J, Michaelsson K, Aspenberg P (2011) Bisphosphonate use and atypical fractures of the femoral shaft. N Engl J Med 364:1728–1737CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of Orthopaedic SurgerySeoul National University Bundang HospitalSeongnamRepublic of Korea
  2. 2.Department of Endocrinology, Internal MedicineSoonchunhyang University HospitalSeoulRepublic of Korea
  3. 3.Graduate School of MedicineHokkaido UniversitySapporoJapan
  4. 4.Department of Biology & Public HealthMokwon UniversityDaejeonRepublic of Korea
  5. 5.Department of Internal MedicineWonkwang University Sanbon HospitalGunpoRepublic of Korea
  6. 6.Department of Internal MedicineCatholic Kwandong University College of Medicine, International St. Mary’s HospitalIncheonRepublic of Korea
  7. 7.Department of Orthopaedic Surgery, School of Medicine, Konkuk University Medical CenterKonkuk UniversitySeoulRepublic of Korea
  8. 8.College of Pharmacy and Gachon Institute of Pharmaceutical SciencesGachon UniversityIncheonRepublic of Korea
  9. 9.Department of Orthopaedic Surgery, School of MedicineChung-Ang UniversitySeoulRepublic of Korea

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