Archives of Osteoporosis

, 13:130 | Cite as

FRAX® based intervention thresholds for management of osteoporosis in Singaporean women

  • M. ChandranEmail author
  • E. V. McCloskey
  • W. P. P. Thu
  • S. Logan
  • Y. Hao
  • D. Tay
  • W. C. Ang
  • T. K. K. Aung
  • K. S. Choo
  • A. Ali
  • S. X. Yan
  • X. F. Huang
  • X. M. Liu
  • E. L. Yong
  • S. Lekamwasam
Original Article



Potential FRAX®-based major osteoporotic fracture (MOF) and hip fracture (HF) intervention thresholds (ITs) for postmenopausal Singaporean women were explored. Age-dependent ethnic-specific and weighted mean ITs progressively increased with increasing age. Fixed ITs were derived via discriminatory value analysis. MOF and HF ITs with highest the Youden index were chosen as optimal.


We aimed to explore FRAX®-based intervention thresholds (ITs) to potentially guide osteoporosis treatment in Singapore, a multi-ethnic nation.


One thousand and one Singaporean postmenopausal community-dwelling women belonging to Chinese, Malay and Indian ethnicities underwent clinical risk factor (CRF) and BMD assessment. FRAX® major osteoporotic fracture (MOF) and hip fracture (HF) probabilities were calculated using ethnic-specific models. We employed the translational logic adopted by NOGG (UK), whereby osteoporosis treatment is recommended to any postmenopausal woman whose fracture probability based on other CRFs is similar to or exceeds that of an age-matched woman with a fracture. Using the same logic, ethnic-specific and mean weighted age-dependent ITs were computed. Employing these age-dependent ITs as a reference, the performance of fixed (age-independent) ITs were examined using ROC curves and discriminatory analysis, with the highest Youden index (YI) (sensitivity + specificity − 1) used to identify the optimal MOF and HF ITs.


The mean age was 58.9 (6.9) years. Seven hundred and eighty-nine (79%) women were Chinese, 136 (13.5%) Indian and 76 (7.5%) Malay. Age-dependent MOF ITs ranged from 3.1 to 33%, 2.5 to 17% and 2.5 to 16% whilst HF ITs ranged from 0.7 to 17%, 0.4 to 6% and 0.4 to 6.3% in Chinese, Malay and Indian women, respectively, between the ages of 50 and 90 years. The weighted age-dependent MOF and HF ITs ranged from 2.9% and 0.6%, respectively, at the age of 50, to 28% and 14% at 90 years of age. Fixed MOF/HF ITs of 5.5%/1%, 2.5%/1% and 2.5%/0.25% were identified as the most optimal by the highest YI in Chinese, Malay and Indian women, respectively. Fixed MOFP and HF ITs of 4% and 1%, respectively, were found to be most optimal on the weighted means analysis.


The ITs for osteoporosis treatment in Singapore show marked variations across ethnicities. Weighted mean thresholds may overcome the dilemma of intervening at different thresholds for different ethnicities. Choosing fixed ITs may have to involve trade-offs between sensitivity and specificity. FRAX®-based age-dependent or the fixed intervention thresholds suggested as an alternative to be considered for use in Singapore though further studies on the societal and health economic impacts of choosing these thresholds in Singapore are needed.


Fragility fracture FRAX Guidelines Intervention threshold Osteoporosis Singapore Treatment threshold 


Compliance with ethical standards

Conflicts of interest



  1. 1.
    Assessment of fracture risk and its application to screening for postmenopausal osteoporosis (1994) Report of a WHO Study Group. World Health Organ Tech Rep Ser 843:1–129Google Scholar
  2. 2.
    Kanis JA, Oden A, Johnell O, Johansson H, De Laet C, Brown J et al (2007) The use of clinical risk factors enhances the performance of BMD in the prediction of hip and osteoporotic fractures in men and women. Osteoporos Int 18(8):1033–1046. CrossRefPubMedGoogle Scholar
  3. 3.
    Marques A, Ferreira RJO, Santos E, Loza E, Carmona L, da Silva JAP et al (2015) The accuracy of osteoporotic fracture risk prediction tools: a systematic review and meta-analysis. Ann Rheum Dis 74(11):1958–1967. CrossRefPubMedGoogle Scholar
  4. 4.
    Compston J, Cooper A, Cooper C, Gittoes N, Gregson C, Harvey N et al (2017) UK clinical guideline for the prevention and treatment of osteoporosis. Arch Osteoporos 12(1):43CrossRefGoogle Scholar
  5. 5.
    Camacho PM, Petak SM, Binkley N, Clarke BL, Harris ST, Hurley DL, Kleerekoper M, Lewiecki EM, Miller PD, Narula HS, Pessah-Pollack R, Tangpricha V, Wimalawansa SJ, Watts NB (2016) American association of clinical endocrinologists and American college of endocrinology clinical practice guidelines for the Diagnosis and treatment of postmenopausal osteoporosis - 2016. Endocr Pract 22(Suppl 4):1–42. CrossRefPubMedGoogle Scholar
  6. 6.
    Cosman F, de Beur SJ, LeBoff MS, Lewiecki EM, Tanner B, Randall S et al (2014) Clinician’s guide to prevention and treatment of osteoporosis. Osteoporos Int 25(10):2359–2381. CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Wainwright SA, Marshall LM, Ensrud KE, Cauley JA, Black DM, Hillier TA, Hochberg MC, Vogt MT, Orwoll ES (2005) Hip fracture in women without osteoporosis. J Clin Endocrinol Metab 90(5):2787–2793. CrossRefPubMedGoogle Scholar
  8. 8.
    Kanis JA, Borgstrom F, De Laet C, Johansson H, Johnell O, Jonsson B et al (2005) Assessment of fracture risk. Osteoporos Int 16(6):581–589. CrossRefPubMedGoogle Scholar
  9. 9.
    Shepstone L, Lenaghan E, Cooper C, Clarke S, Fong-Soe-Khioe R, Fordham R et al (2018) Screening in the community to reduce fractures in older women (SCOOP): a randomised controlled trial. Lancet (London, England) 391(10122):741–747. CrossRefGoogle Scholar
  10. 10.
    McCloskey EV, Johansson H, Oden A, Austin M, Siris E, Wang A et al (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(7):1480–1486. CrossRefPubMedGoogle Scholar
  11. 11.
    Lippuner K, Johansson H, Borgström F, Kanis JA, Rizzoli R (2012) Cost-effective intervention thresholds against osteoporotic fractures based on FRAX® in Switzerland. Osteoporos Int 23:2579–2589. CrossRefPubMedGoogle Scholar
  12. 12.
    Zhang Z, Ou Y, Sheng Z, Liao E (2014) How to decide intervention thresholds based on FRAX in central south Chinese postmenopausal women. Endocrine 45(2):195–197. CrossRefPubMedGoogle Scholar
  13. 13.
    Tosteson ANA, Melton LJ, Dawson-Hughes B, Baim S, Favus MJ, Khosla S et al (2008) Cost-effective osteoporosis treatment thresholds: the United States perspective. Osteoporos Int 19(4):437–447. CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    Kanis JA, McCloskey EV, Johansson H, Strom O, Borgstrom F, Oden A et al (2008) Case finding for the management of osteoporosis with FRAX--assessment and intervention thresholds for the UK. Osteoporos Int 19(10):1395–1408. CrossRefPubMedGoogle Scholar
  15. 15.
    Chakhtoura M, Leslie WD, McClung M, Cheung AM, Fuleihan GEH (2017) The FRAX-based Lebanese osteoporosis treatment guidelines: rationale for a hybrid model. Osteoporos Int 28(1):127–137. CrossRefPubMedGoogle Scholar
  16. 16.
    Cheung E, Cheung CL, Kung AWC, Tan KCB (2014) Possible FRAX-based intervention thresholds for a cohort of Chinese postmenopausal women. Osteoporos Int 25(3):1017–1023. CrossRefPubMedGoogle Scholar
  17. 17.
    Lekamwasam S (2013) Sri Lankan FRAX model and country-specific intervention thresholds. Arch Osteoporos 8:148CrossRefGoogle 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.
    Korthoewer D, Chandran M, Endocrine and Metabolic Society of Singapore (2012) Osteoporosis management and the utilization of FRAX®: a survey amongst health care professionals of the Asia-Pacific. Arch Osteoporos 7(1–2):193–200CrossRefGoogle Scholar
  20. 20.
    Thu WPP, Logan SJS, Lim CW, Wang YL, Cauley JA, Yong EL et al (2018) Cohort profile: the Integrated Women’s Health Programme (IWHP): a study of key health issues of midlife Singaporean women. Int J Epidemiol 47(2):389–390f. CrossRefPubMedGoogle Scholar
  21. 21.
    Leong KH, Feng PH (1997) Bone mineral density measurements using the Hologic QD2000 in 175 Singaporean women aged 20–80. Singap Med J 38(1):25–26Google Scholar
  22. 22.
    Gao H, Salim A, Lee J, Tai ES, van Dam RM (2012) Can body fat distribution, adiponectin levels and inflammation explain differences in insulin resistance between ethnic Chinese, Malays and Asian Indians? Int J Obes 36(8):1086–1093. CrossRefGoogle Scholar
  23. 23.
    Bewick V, Cheek L, Ball J (2004) Statistics review 13: receiver operating characteristic curves. Crit Care 8(6):508–512. CrossRefPubMedPubMedCentralGoogle Scholar
  24. 24.
    YOUDEN WJ (1950) Index for rating diagnostic tests. Cancer 3(1):32–35.<32::AID-CNCR2820030106>3.0.CO;2-3 CrossRefPubMedGoogle Scholar
  25. 25.
    McCloskey E, Kanis JA, Johansson H, Harvey N, Odén 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(8):2091–2099. CrossRefPubMedGoogle Scholar
  26. 26.
    Kanis JA, McCloskey EV, Johansson H, Cooper C, Rizzoli R, Reginster JY et al (2013) European guidance for the diagnosis and management of osteoporosis in postmenopausal women. Osteoporos Int 24(1):23–57. CrossRefPubMedGoogle Scholar
  27. 27.
    Koh LK, Saw SM, Lee JJ, Leong KH, Lee J, National Working Committee on Osteoporosis et al (2001) Hip fracture incidence rates in Singapore 1991–1998. Osteoporos Int 12(4):311–318. CrossRefPubMedGoogle Scholar
  28. 28.
    Kanis JA, Bianchi G, Bilezikian JP, Kaufman JM, Khosla S, Orwoll E, Seeman E (2011) Towards a diagnostic and therapeutic consensus in male osteoporosis. Osteoporos Int 22(11):2789–2798. CrossRefPubMedPubMedCentralGoogle Scholar
  29. 29.
    Levis S, Theodore G (2012) Summary of AHRQ’s comparative effectiveness review of treatment to prevent fractures in men and women with low bone density or osteoporosis: update of the 2007 report. J Manag Care Pharm 18(4 Suppl B):S1–S15 discussion S13PubMedGoogle Scholar
  30. 30.
    Ensrud KE, Taylor BC, Peters KW, Gourlay ML, Donaldson MG, Leslie WD et al (2014) Implications of expanding indications for drug treatment to prevent fracture in older men in United States: cross sectional and longitudinal analysis of prospective cohort study. BMJ 349:g4120CrossRefGoogle Scholar
  31. 31.
    Eichler HG, Kong SX, Gerth WC, Mavros P, Jönsson B (2004) Use of cost-effectiveness analysis in health-care resource allocation decision-making: how are cost-effectiveness thresholds expected to emerge? Value Health 7(5):518–528. CrossRefPubMedGoogle Scholar
  32. 32.
    Harvey NC, McCloskey E, Kanis JA, Compston J, Cooper C (2018) Cost-effective but clinically inappropriate: new NICE intervention thresholds in osteoporosis (Technology Appraisal 464). Osteoporos Int 29(7):1511–1513. CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© International Osteoporosis Foundation and National Osteoporosis Foundation 2018

Authors and Affiliations

  • M. Chandran
    • 1
    Email author
  • E. V. McCloskey
    • 2
    • 3
  • W. P. P. Thu
    • 4
  • S. Logan
    • 4
  • Y. Hao
    • 5
  • D. Tay
    • 6
  • W. C. Ang
    • 7
  • T. K. K. Aung
    • 6
  • K. S. Choo
    • 8
  • A. Ali
    • 6
  • S. X. Yan
    • 9
  • X. F. Huang
    • 1
  • X. M. Liu
    • 1
  • E. L. Yong
    • 4
  • S. Lekamwasam
    • 10
  1. 1.Osteoporosis and Bone Metabolism Unit, Department of EndocrinologySingapore General Hospital, ACADEMIASingaporeSingapore
  2. 2.MRC-Arthritis UK Centre for Integrated Research into Musculoskeletal Ageing (CIMA), Mellanby Centre for Bone Research, Department of Oncology and MetabolismUniversity of SheffieldSheffieldUK
  3. 3.Metabolic Bone Centre, Northern General HospitalUniversity of SheffieldSheffieldUK
  4. 4.Department of Obstetrics and GynaecologyNational University of SingaporeSingaporeSingapore
  5. 5.Health Services Research Unit (HSRU), Division of MedicineSingapore General HospitalSingaporeSingapore
  6. 6.Division of MedicineSengkang General HospitalSingaporeSingapore
  7. 7.Division of MedicineSingapore General HospitalSingaporeSingapore
  8. 8.Department of EndocrinologySingapore General HospitalSingaporeSingapore
  9. 9.Department of Nuclear Medicine and Molecular ImagingSingapore General HospitalSingaporeSingapore
  10. 10.Faculty of MedicineUniversity of RuhunaGalleSri Lanka

Personalised recommendations