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Risk of fracture incidence in prostate cancer survivors: a nationwide cohort study in South Korea

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Abstract

Purpose

We analyzed the risk of fracture in prostate cancer (PC) survivors compared to that in the general population in South Korea and according to the primary treatment.

Methods

From 2007 to 2013, a total of 41,733 PC survivors newly diagnosed with PC in South Korea were identified and matched to non-cancer controls. Cox proportional hazards regression analysis was performed to determine the relative risk of fracture.

Results

Compared to the matched controls, PC survivors had a higher risk of fracture (adjusted hazard ratio (aHR) 1.39; 95% confidence interval (CI) 1.33–1.45). Compared to the matched controls, the active surveillance/watchful waiting and radiotherapy group showed a similar risk of fracture (aHR 1.08; 95% CI 0.98–1.20, and aHR 1.04; 95% CI 0.63–1.73, respectively). PC survivors who underwent surgery showed a lower risk of fracture (aHR 0.89; 95% CI 0.82–0.96), while those who underwent surgery + androgen deprivation therapy (ADT) (aHR 1.41; 95% CI 1.26–1.57), radiotherapy + ADT (aHR 1.86; 95% CI 1.50–2.32), and only ADT (aHR 1.92; 95% CI 1.82–2.02) showed a higher risk of fracture than the control group.

Conclusion

The risk of fracture differed according to the primary treatment method for PC; survivors who underwent surgery had a lower risk of fracture compared to that of the general population. However, PC survivors treated with ADT showed a higher risk of fracture than the other PC treatment groups or the general population. Therefore, more attention and preventive bone care are required for PC survivors who receive ADT.

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Data availability

Not applicable (because access to the big data requires permission of KNHIS).

Abbreviations

AS/WW:

Active surveillance/watchful waiting

RT:

Radiotherapy

ADT:

Androgen deprivation therapy

BMD:

Bone mineral density

KNHIS:

Korean National Health Insurance Service

ICD-10:

International Classification of Disease, 10th revision

LHRH:

Luteinizing hormone-releasing hormone

aHR:

Adjusted hazard ratio

CI:

Confidence interval

References

  1. Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A (2018) Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 68:394–424

    Article  PubMed  Google Scholar 

  2. Siegel RL, Miller KD, Jemal A (2016) Cancer statistics, 2016. CA Cancer J Clin 66:7–30

    Article  PubMed  Google Scholar 

  3. Miller KD, Siegel RL, Lin CC, Mariotto AB, Kramer JL, Rowland JH, Stein KD, Alteri R, Jemal A (2016) Cancer treatment and survivorship statistics, 2016. CA Cancer J Clin 66:271–289

    Article  PubMed  Google Scholar 

  4. Jung KW, Won YJ, Kong HJ, Lee ES (2019) Cancer statistics in Korea: incidence, mortality, survival, and prevalence in 2016. Cancer Res Treat 51:417–430

    Article  PubMed  PubMed Central  Google Scholar 

  5. Miller KD, Nogueira L, Mariotto AB, Rowland JH, Yabroff KR, Alfano CM, Jemal A, Kramer JL, Siegel RL (2019) Cancer treatment and survivorship statistics, 2019. CA Cancer J Clin 69:363–385

    Article  PubMed  Google Scholar 

  6. Lopez AM, Pena MA, Hernandez R, Val F, Martin B, Riancho JA (2005) Fracture risk in patients with prostate cancer on androgen deprivation therapy. Osteoporos Int 16:707–711

    Article  CAS  PubMed  Google Scholar 

  7. Wallander M, Axelsson KF, Lundh D, Lorentzon M (2019) Patients with prostate cancer and androgen deprivation therapy have increased risk of fractures-a study from the fractures and fall injuries in the elderly cohort (FRAILCO). Osteoporos Int 30:115–125

    Article  CAS  PubMed  Google Scholar 

  8. Wang A, Obertova Z, Brown C, Karunasinghe N, Bishop K, Ferguson L, Lawrenson R (2015) Risk of fracture in men with prostate cancer on androgen deprivation therapy: a population-based cohort study in New Zealand. BMC Cancer 15:837

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  9. Oefelein MG, Ricchuiti V, Conrad W, Seftel A, Bodner D, Goldman H, Resnick M (2001) Skeletal fracture associated with androgen suppression induced osteoporosis: the clinical incidence and risk factors for patients with prostate cancer. J Urol 166:1724–1728

    Article  CAS  PubMed  Google Scholar 

  10. Alibhai SM, Duong-Hua M, Cheung AM, Sutradhar R, Warde P, Fleshner NE, Paszat L (2010) Fracture types and risk factors in men with prostate cancer on androgen deprivation therapy: a matched cohort study of 19,079 men. J Urol 184:918–923

    Article  PubMed  Google Scholar 

  11. Wu CT, Yang YH, Chen PC, Chen MF, Chen WC (2015) Androgen deprivation increases the risk of fracture in prostate cancer patients: a population-based study in Chinese patients. Osteoporos Int 26:2281–2290

    Article  CAS  PubMed  Google Scholar 

  12. Melton LJ 3rd, Lieber MM, Atkinson EJ, Achenbach SJ, Zincke H, Therneau TM, Khosla S (2011) Fracture risk in men with prostate cancer: a population-based study. J Bone Miner Res 26:1808–1815

    Article  PubMed  Google Scholar 

  13. Abrahamsen B, Nielsen MF, Eskildsen P, Andersen JT, Walter S, Brixen K (2007) Fracture risk in Danish men with prostate cancer: a nationwide register study. BJU Int 100:749–754

    Article  PubMed  Google Scholar 

  14. Thorstenson A, Bratt O, Akre O, Hellborg H, Holmberg L, Lambe M, Bill-Axelson A, Stattin P, Adolfsson J (2012) Incidence of fractures causing hospitalisation in prostate cancer patients: results from the population-based PCBaSe Sweden. Eur J Cancer 48:1672–1681

    Article  PubMed  Google Scholar 

  15. Jefferies ER, Bahl A, Hounsome L, Eylert MF, Verne J, Persad RA, collaborative P (2016) Admissions to hospital due to fracture in England in patients with prostate cancer treated with androgen-deprivation therapy - do we have to worry about the hormones? BJU Int 118:416–422

    Article  CAS  PubMed  Google Scholar 

  16. Cheol Seong S, Kim YY, Khang YH, Heon Park J, Kang HJ, Lee H, Do CH, Song JS, Hyon Bang J, Ha S, Lee EJ, Ae Shin S (2017) Data resource profile: the National Health Information Database of the National Health Insurance Service in South Korea. Int J Epidemiol 46:799–800

    PubMed  Google Scholar 

  17. Lee H, Cho J, Shin DW, Lee SP, Hwang SS, Oh J, Yang HK, Hwang SH, Son KY, Chun SH, Cho BL, Guallar E (2015) Association of cardiovascular health screening with mortality, clinical outcomes, and health care cost: a nationwide cohort study. Prev Med 70:19–25

    Article  PubMed  Google Scholar 

  18. Shin DW, Cho B, Guallar E (2016) Korean national health insurance database. JAMA Intern Med 176:138

    Article  PubMed  Google Scholar 

  19. Lee J, Lee JS, Park SH, Shin SA, Kim K (2017) Cohort profile: the National Health Insurance Service-National Sample Cohort (NHIS-NSC), South Korea. Int J Epidemiol 46:e15

    PubMed  Google Scholar 

  20. Kang J, Shin DW, Han K, Park SH, Lee WG, Yoo JE, Woo SH, Park J (2020) Risk of dementia in prostate cancer survivors: a nationwide cohort study in Korea. Curr Probl Cancer 100578

  21. Kim HY, Ha YC, Kim TY, Cho H, Lee YK, Baek JY, Jang S (2017) Healthcare costs of osteoporotic fracture in Korea: information from the National Health Insurance Claims Database, 2008-2011. J Bone Metab 24:125–133

    Article  PubMed  PubMed Central  Google Scholar 

  22. Lix LM, Azimaee M, Osman BA, Caetano P, Morin S, Metge C, Goltzman D, Kreiger N, Prior J, Leslie WD (2012) Osteoporosis-related fracture case definitions for population-based administrative data. BMC Public Health 12:301

    Article  PubMed  PubMed Central  Google Scholar 

  23. Jeong SM, Shin DW, Han K, Jung JH, Chun S, Jung HW, Son KY (2019) Timed up-and-go test is a useful predictor of fracture incidence. Bone 127:474–481

    Article  PubMed  Google Scholar 

  24. Sundararajan V, Henderson T, Perry C, Muggivan A, Quan H, Ghali WA (2004) New ICD-10 version of the Charlson comorbidity index predicted in-hospital mortality. J Clin Epidemiol 57:1288–1294

    Article  PubMed  Google Scholar 

  25. Nuttall M, van der Meulen J, Emberton M (2006) Charlson scores based on ICD-10 administrative data were valid in assessing comorbidity in patients undergoing urological cancer surgery. J Clin Epidemiol 59:265–273

    Article  PubMed  Google Scholar 

  26. Anuurad E, Shiwaku K, Nogi A, Kitajima K, Enkhmaa B, Shimono K, Yamane Y (2003) The new BMI criteria for asians by the regional office for the western pacific region of WHO are suitable for screening of overweight to prevent metabolic syndrome in elder Japanese workers. J Occup Health 45:335–343

    Article  PubMed  Google Scholar 

  27. Lee EA, Shin DW, Yoo JH, Ko HY, Jeong SM (2019) Anemia and risk of fractures in older Korean adults: a Nationwide population-based study. J Bone Miner Res 34:1049–1057

    Article  PubMed  Google Scholar 

  28. Valderrabano RJ, Linares MI (2018) Diabetes mellitus and bone health: epidemiology, etiology and implications for fracture risk stratification. Clin Diabetes Endocrinol 4:9

    Article  PubMed  PubMed Central  Google Scholar 

  29. Pérez-Castrillón JL, Martín-Escudero JC, Manzanares PA, Sancho RC, Zamora SI, Alonso MG (2005) Hypertension as a risk factor for hip fracture. Am J Hypertens 18:146–147

    Article  PubMed  Google Scholar 

  30. Helin-Salmivaara A, Korhonen MJ, Lehenkari P, Junnila SY, Neuvonen PJ, Ruokoniemi P, Huupponen R (2012) Statins and hip fracture prevention--a population based cohort study in women. PLoS One 7:e48095

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Daya N, Voskertchian A, Schneider ALC, Ballew S, McAdams DeMarco M, Coresh J, Appel LJ, Selvin E, Grams ME (2016) Kidney function and fracture risk: the Atherosclerosis Risk in Communities (ARIC) study. Am J Kidney Dis 67:218–226

    Article  PubMed  Google Scholar 

  32. Zhang X, Yu Z, Yu M, Qu X (2015) Alcohol consumption and hip fracture risk. Osteoporos Int 26:531–542

    Article  CAS  PubMed  Google Scholar 

  33. Hernigou J, Schuind F (2019) Tobacco and bone fractures: a review of the facts and issues that every orthopaedic surgeon should know. Bone Joint Res 8:255–265

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Armenian SH, Xu L, Ky B, Sun C, Farol LT, Pal SK, Douglas PS, Bhatia S, Chao C (2016) Cardiovascular disease among survivors of adult-onset cancer: a community-based retrospective cohort study. J Clin Oncol 34:1122–1130

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Sharma A, Sinha RJ, Singh V, Garg G, Agarwal S, Pandey S (2019) Implications of the fracture risk assessment algorithm for the assessment and improvement of bone health in patients with prostate cancer: a comprehensive review. Turk J Urol

  36. Teoh JY, Chiu PK, Chan SY, Poon DM, Cheung HY, Hou SS, Ng CF (2015) Androgen deprivation therapy, diabetes and poor physical performance status increase fracture risk in Chinese men treated for prostate cancer. Aging Male 18:180–185

    Article  PubMed  CAS  Google Scholar 

  37. Graham-Steed TR, Soulos PR, Dearing N, Concato J, Tinetti ME, Gross CP (2014) Development and validation of a prognostic index for fracture risk in older men undergoing prostate cancer treatment. J Geriatr Oncol 5:343–351

    Article  PubMed  PubMed Central  Google Scholar 

  38. Shahinian VB, Kuo YF, Freeman JL, Goodwin JS (2005) Risk of fracture after androgen deprivation for prostate cancer. N Engl J Med 352:154–164

    Article  CAS  PubMed  Google Scholar 

  39. Grey A (2016) Osteoporosis and fracture risk in men with prostate cancer. Eur Urol 69:1026–1027

    Article  PubMed  Google Scholar 

  40. Hatano T, Oishi Y, Furuta A, Iwamuro S, Tashiro K (2000) Incidence of bone fracture in patients receiving luteinizing hormone-releasing hormone agonists for prostate cancer. BJU Int 86:449–452

    Article  CAS  PubMed  Google Scholar 

  41. Morgans AK, Smith MR, O'Malley AJ, Keating NL (2013) Bone density testing among prostate cancer survivors treated with androgen-deprivation therapy. Cancer 119:863–870

    Article  PubMed  Google Scholar 

  42. Gralow JR, Biermann JS, Farooki A et al (2013) NCCN task force report: bone health in Cancer care. J Natl Compr Canc Netw 11(Suppl 3):S1–S50 quiz S51

    Article  PubMed  Google Scholar 

  43. Watts NB, Adler RA, Bilezikian JP, Drake MT, Eastell R, Orwoll ES, Finkelstein JS, Endocrine S (2012) Osteoporosis in men: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab 97:1802–1822

    Article  CAS  PubMed  Google Scholar 

  44. Skolarus TA, Wolf AM, Erb NL, Brooks DD, Rivers BM, Underwood W 3rd, Salner AL, Zelefsky MJ, Aragon-Ching JB, Slovin SF, Wittmann DA, Hoyt MA, Sinibaldi VJ, Chodak G, Pratt-Chapman ML, Cowens-Alvarado RL (2014) American Cancer Society prostate cancer survivorship care guidelines. CA Cancer J Clin 64:225–249

    Article  PubMed  Google Scholar 

  45. Alibhai SMH, Zukotynski K, Walker-Dilks C, Emmenegger U, Finelli A, Morgan SC, Hotte SJ, Tomlinson GA, Winquist E (2017) Bone health and bone-targeted therapies for nonmetastatic prostate cancer: a systematic review and meta-analysis. Ann Intern Med 167:341–350

    Article  PubMed  Google Scholar 

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Acknowledgments

This study used National Health Insurance Service (NHIS) data (NHIS-2020-1-115 made by NHIS.

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Authors and Affiliations

Authors

Contributions

Hyun Bin Shin: investigation, visualization, writing—original draft. Hyun Sik Park: supervision, validation. Jung Eun Yoo: supervision, validation, writing—review and editing. Kyungdo Han: data curation, formal analysis, software. Sang Hyun Park: data curation, formal analysis, software. Dong Wook Shin: conceptualization, investigation, methodology, resources, supervision, writing—review and editing. Jinsung Park: conceptualization, investigation, methodology, resources, supervision, writing—review and editing.

Corresponding authors

Correspondence to Dong Wook Shin or Jinsung Park.

Ethics declarations

Conflicts of interest

None.

Ethics approval

For this type of study formal consent is not required. (IRB No. 2018-09-001).

Consent to participate

Waived because our study used deidentified data of KNHIS database.

Consent for publication

Yes. Corresponding author, Dr. Jinsung Park, has full responsibility for publication.

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Not applicable.

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Shin, H.B., Park, H.S., Yoo, J.E. et al. Risk of fracture incidence in prostate cancer survivors: a nationwide cohort study in South Korea. Arch Osteoporos 15, 110 (2020). https://doi.org/10.1007/s11657-020-00785-6

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