Underestimated fracture risk in postmenopausal women—application of the hybrid intervention threshold

  • Y. Wang
  • S. Yu
  • C. Hsu
  • C. TsaiEmail author
  • T. ChengEmail author
Original Article



This study evaluated the fragility fracture risk of Taiwanese postmenopausal women with osteopenia. With the incorporation of FRAX and hybrid intervention threshold (HIT), 25% of the participants had high fracture risk. We suggest intervention for fragility fracture for postmenopausal women should be guided by FRAX and HIT instead of bone mineral density alone.


To explore the risk of fragility fracture in Taiwanese postmenopausal women with osteopenia using the hybrid intervention threshold (HIT) and Fracture Risk Assessment tool (FRAX).


The Taiwan Osteoporosis Association (TOA) conducted a nationwide bone mineral density (BMD) survey between 2008 and 2011 using a bus equipped with a dual-energy X-ray absorptiometry (DXA) machine. All participants completed a structured questionnaire, which included the elements in the FRAX. Based on the results, the group made up of postmenopausal women with osteopenia was identified. In order to explore the risk of fragility fracture by HIT and FRAX among Taiwan postmenopausal women with osteopenia, the 10-year probability of fracture (FRAX score) and individual intervention threshold (IIT) in this group were calculated. If the FRAX score of a participant was higher than or equal to the IIT or fixed intervention threshold (FIT), the participant was considered as above the HIT (HIT could be reached by being over a threshold at either major osteoporotic fracture or hip fracture) and categorized as having a high FRAX fracture risk.


A total of 13,068 postmenopausal women were enrolled in the program. A total of 5743 (43.9%) participants had osteopenia, of which 1434 (25.0%) had high FRAX fracture risk.


One quarter of Taiwanese postmenopausal women with osteopenia had high fragility fracture risk evaluated by FRAX and HIT. Due to the poor sensitivity of BMD for fragility fracture, we suggest that intervention for fragility fracture for postmenopausal women should also be guided by FRAX and HIT instead of BMD alone.


FRAX Intervention threshold Menopause Osteopenia 



We are indebted to the TOA for authorizing the use and management of the database. We are also grateful to the Merck Sharp & Dohme pharmaceutical company (Taiwan) for allowing us to use the mobile DXA machine during the recruitment period. We also appreciate the help of Hsu MC in performing the statistical analyses.

Funding information

Funding for this work was provided through grant CMRPG8D0651 from the Chang Gung Memorial Hospital (

Compliance with ethical standards

This study was approved by the local Institutional Review Board of Chang Gung Memorial Hospital (102-1878B). All participants provided written informed consent prior to participating in this program.

Conflicts of interest


Supplementary material

198_2019_5201_MOESM1_ESM.docx (1.3 mb)
ESM 1 (DOCX 1371 kb)


  1. 1.
    NIH Consensus Development Panel (2001) Osteoporosis prevention, diagnosis, and therapy. Jama 285:785–795. CrossRefGoogle Scholar
  2. 2.
    Pisani P, Renna MD, Conversano F, Casciaro E, Di Paola M, Quarta E, Muratore M, Casciaro S (2016) Major osteoporotic fragility fractures: risk factor updates and societal impact. World J Orthop 7:171–181. CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Siris ES, Chen YT, Abbott TA, Barrett-Connor E, Miller PD, Wehren LE, Berger ML (2004) Bone mineral density thresholds for pharmacological intervention to prevent fractures. Arch Intern Med 164:1108–1112. CrossRefPubMedGoogle Scholar
  4. 4.
    Kanis JA, Johansson H, Harvey NC, McCloskey EV (2018) A brief history of FRAX. Arch Osteoporos 13:118. CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    Kanis JA, McCloskey EV, Johansson H, Oden A, Strom O, Borgstrom F (2010) Development and use of FRAX in osteoporosis. Osteoporos Int 21(Suppl 2):S407–S413. CrossRefPubMedGoogle Scholar
  6. 6.
    Lin YC, Pan WH (2011) Bone mineral density in adults in Taiwan: results of the Nutrition and Health Survey in Taiwan 2005-2008 (NAHSIT 2005-2008). Asia Pac J Clin Nutr 20:283–291 1 PubMedGoogle Scholar
  7. 7.
    Lin HH, Huang CY, Hwang LC (2018) Association between metabolic syndrome and osteoporosis in Taiwanese middle-aged and elderly participants. Arch Osteoporos 13:48. CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Drug payment criteria. Chapter 5. Hormones & drugs affecting hormonal mechanism. Section 5.6 Anti-osteoporotic medications. National Health Insurance Administration Ministry of Health and Welfare. Assessed 17 April 2019
  9. 9.
    Kanis JA, Harvey NC, Cooper C, Johansson H, Oden A, McCloskey EV (2016) A systematic review of intervention thresholds based on FRAX: a report prepared for the National Osteoporosis Guideline Group and the International Osteoporosis Foundation. Arch Osteoporos 11:25. CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Dimai HP (2017) Use of dual-energy X-ray absorptiometry (DXA) for diagnosis and fracture risk assessment; WHO-criteria, T- and Z-score, and reference databases. Bone 104:39–43. CrossRefPubMedGoogle Scholar
  11. 11.
    WHO scientific group on the assessment of osteoporosis at primary health care level Assessed 17 April 2019
  12. 12.
    FRAX (Fracture Risk Assessment Tool): Taiwan. Assessed 17 April 2019
  13. 13.
    Cosman F, de Beur SJ, LeBoff MS, Lewiecki EM, Tanner B, Randall S, Lindsay R (2014) Clinician‘s guide to prevention and treatment of osteoporosis. Osteoporos Int 25:2359–2381. CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    Hwang JS, Chan DC, Chen JF, Cheng TT, Wu CH, Soong YK, Tsai KS, Yang RS (2014) Clinical practice guidelines for the prevention and treatment of osteoporosis in Taiwan: summary. J Bone Miner Metab 32:10–16. CrossRefPubMedGoogle Scholar
  15. 15.
    Kanis JA, McCloskey EV, Harvey NC, Johansson H, Leslie WD (2015) Intervention thresholds and the diagnosis of osteoporosis. J Bone Miner Res 30:1747–1753. CrossRefPubMedGoogle Scholar
  16. 16.
    Kanis JA, Johansson H, Oden A, McCloskey EV (2012) The distribution of FRAX((R))-based probabilities in women from Japan. J Bone Miner Metab 30:700–705. CrossRefPubMedGoogle Scholar
  17. 17.
    McCloskey E, Kanis JA, Johansson H, Harvey N, Oden A, Cooper A, Cooper C, Francis RM, Reid DM, Marsh D, Selby P, Thompson F, Hewitt S, Compston J (2015) FRAX-based assessment and intervention thresholds--an exploration of thresholds in women aged 50 years and older in the UK. Osteoporos Int 26:2091–2099. CrossRefPubMedGoogle Scholar
  18. 18.
    Orimo H, Nakamura T, Hosoi T, Iki M, Uenishi K, Endo N, Ohta H, Shiraki M, Sugimoto T, Suzuki T, Soen S, Nishizawa Y, Hagino H, Fukunaga M, Fujiwara S (2012) Japanese 2011 guidelines for prevention and treatment of osteoporosis--executive summary. Arch Osteoporos 7:3–20. CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    Kanis JA, McCloskey EV, Johansson H, Strom O, Borgstrom F, Oden A (2008) Case finding for the management of osteoporosis with FRAX--assessment and intervention thresholds for the UK. Osteoporos Int 19:1395–1408. CrossRefPubMedGoogle Scholar
  20. 20.
    Chen JS, Simpson JM, Blyth FM, March LM (2014) Managing osteoporosis with FRAX(R) in Australia: proposed new treatment thresholds from the 45&Up Study cohort. Bone 69:148–153. CrossRefPubMedGoogle Scholar
  21. 21.
    Johansson H, Azizieh F, Al Ali N, Alessa T, Harvey NC, McCloskey E, Kanis JA (2017) FRAX- vs. T-score-based intervention thresholds for osteoporosis. Osteoporos Int 28:3099–3105. CrossRefPubMedPubMedCentralGoogle Scholar
  22. 22.
    Lekamwasam S, Adachi JD, Agnusdei D, Bilezikian J, Boonen S, Borgstrom F, Cooper C, Diez Perez A, Eastell R, Hofbauer LC, Kanis JA, Langdahl BL, Lesnyak O, Lorenc R, McCloskey E, Messina OD, Napoli N, Obermayer-Pietsch B, Ralston SH, Sambrook PN, Silverman S, Sosa M, Stepan J, Suppan G, Wahl DA, Compston JE (2012) A framework for the development of guidelines for the management of glucocorticoid-induced osteoporosis. Osteoporos Int 23:2257–2276. CrossRefPubMedGoogle Scholar
  23. 23.
    Black DM, Delmas PD, Eastell R, Reid IR, Boonen S, Cauley JA, Cosman F, Lakatos P, Leung PC, Man Z, Mautalen C, Mesenbrink P, Hu H, Caminis J, Tong K, Rosario-Jansen T, Krasnow J, Hue TF, Sellmeyer D, Eriksen EF, Cummings SR (2007) Once-yearly zoledronic acid for treatment of postmenopausal osteoporosis. N Engl J Med 356:1809–1822. CrossRefGoogle Scholar
  24. 24.
    Cummings SR, San Martin J, McClung MR, Siris ES, Eastell R, Reid IR, Delmas P, Zoog HB, Austin M, Wang A, Kutilek S, Adami S, Zanchetta J, Libanati C, Siddhanti S, Christiansen C (2009) Denosumab for prevention of fractures in postmenopausal women with osteoporosis. N Engl J Med 361:756–765. CrossRefPubMedGoogle Scholar
  25. 25.
    Liberman UA, Weiss SR, Broll J, Minne HW, Quan H, Bell NH, Rodriguez-Portales J, Downs RW Jr, Dequeker J, Favus M (1995) Effect of oral alendronate on bone mineral density and the incidence of fractures in postmenopausal osteoporosis. The Alendronate Phase III Osteoporosis Treatment Study Group. N Engl J Med 333:1437–1443. CrossRefPubMedGoogle Scholar
  26. 26.
    Neer RM, Arnaud CD, Zanchetta JR, Prince R, Gaich GA, Reginster JY, Hodsman AB, Eriksen EF, Ish-Shalom S, Genant HK, Wang O, Mitlak BH (2001) Effect of parathyroid hormone (1-34) on fractures and bone mineral density in postmenopausal women with osteoporosis. N Engl J Med 344:1434–1441. CrossRefPubMedGoogle Scholar
  27. 27.
    Kanis JA, Johansson H, Oden A, McCloskey EV (2009) Bazedoxifene reduces vertebral and clinical fractures in postmenopausal women at high risk assessed with FRAX. Bone 44:1049–1054. CrossRefPubMedGoogle Scholar
  28. 28.
    McCloskey EV, Johansson H, Oden A, Austin M, Siris E, Wang A, Lewiecki EM, Lorenc R, Libanati C, Kanis JA (2012) Denosumab reduces the risk of osteoporotic fractures in postmenopausal women, particularly in those with moderate to high fracture risk as assessed with FRAX. J Bone Miner Res 27:1480–1486. CrossRefPubMedGoogle Scholar
  29. 29.
    McCloskey EV, Johansson H, Oden A, Vasireddy S, Kayan K, Pande K, Jalava T, Kanis JA (2009) Ten-year fracture probability identifies women who will benefit from clodronate therapy--additional results from a double-blind, placebo-controlled randomised study. Osteoporos Int 20:811–817. CrossRefPubMedGoogle Scholar
  30. 30.
    McCloskey EV, Beneton M, Charlesworth D, Kayan K, deTakats D, Dey A, Orgee J, Ashford R, Forster M, Cliffe J, Kersh L, Brazier J, Nichol J, Aropuu S, Jalava T, Kanis JA (2007) Clodronate reduces the incidence of fractures in community-dwelling elderly women unselected for osteoporosis: results of a double-blind, placebo-controlled randomized study. J Bone Miner Res 22:135–141. CrossRefPubMedGoogle Scholar
  31. 31.
    Reid IR, Horne AM, Mihov B, Stewart A, Garratt E, Wong S, Wiessing KR, Bolland MJ, Bastin S, Gamble GD (2018) Fracture prevention with zoledronate in older women with osteopenia. N Engl J Med 379:2407–2416. CrossRefPubMedGoogle Scholar
  32. 32.
    Shepstone L, Lenaghan E, Cooper C, Clarke S, Fong-Soe-Khioe R, Fordham R, Gittoes N, Harvey I, Harvey N, Heawood A, Holland R, Howe A, Kanis J, Marshall T, O'Neill T, Peters T, Redmond N, Torgerson D, Turner D, McCloskey E (2018) Screening in the community to reduce fractures in older women (SCOOP): a randomised controlled trial. Lancet 391:741–747. CrossRefPubMedGoogle Scholar
  33. 33.
    Begum RA, Ali L, Akter J, Takahashi O, Fukui T, Rahman M (2014) Osteopenia and osteoporosis among 16-65 year old women attending outpatient clinics. J Community Health 39:1071–1076. CrossRefPubMedGoogle Scholar
  34. 34.
    Hernlund E, Svedbom A, Ivergard M, Compston J, Cooper C, Stenmark J, McCloskey EV, Jonsson B, Kanis JA (2013) Osteoporosis in the European Union: medical management, epidemiology and economic burden. A report prepared in collaboration with the International Osteoporosis Foundation (IOF) and the European Federation of Pharmaceutical Industry Associations (EFPIA). Arch Osteoporos 8:136. CrossRefPubMedPubMedCentralGoogle Scholar
  35. 35.
    Lee J, Lee S, Jang S, Ryu OH (2013) Age-related changes in the prevalence of osteoporosis according to gender and skeletal site: the Korea National Health and Nutrition Examination Survey 2008-2010. Endocrinol Metab (Seoul) 28:180–191. CrossRefGoogle Scholar
  36. 36.
    Lu YC, Lin YC, Lin YK, Liu YJ, Chang KH, Chieng PU, Chan WP (2016) Prevalence of osteoporosis and low bone mass in older Chinese population based on bone mineral density at multiple skeletal sites. Sci Rep 6:25206. CrossRefPubMedPubMedCentralGoogle Scholar
  37. 37.
    Wright NC, Looker AC, Saag KG, Curtis JR, Delzell ES, Randall S, Dawson-Hughes B (2014) The recent prevalence of osteoporosis and low bone mass in the United States based on bone mineral density at the femoral neck or lumbar spine. J Bone Miner Res 29:2520–2526. CrossRefPubMedPubMedCentralGoogle Scholar
  38. 38.
    Kanis JA, Cooper C, Rizzoli R, Reginster JY (2019) European guidance for the diagnosis and management of osteoporosis in postmenopausal women. Osteoporos Int 30:3–44. CrossRefPubMedGoogle Scholar

Copyright information

© International Osteoporosis Foundation and National Osteoporosis Foundation 2019

Authors and Affiliations

  1. 1.Department of Obstetrics and GynecologyKaohsiung Chang Gung Memorial HospitalKaohsiung CityTaiwan
  2. 2.Division of Rheumatology, Allergy, and Immunology, Department of Internal MedicineKaohsiung Chang Gung Memorial HospitalKaohsiung CityTaiwan
  3. 3.College of MedicineChang Gung UniversityKaohsiung CityTaiwan

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