Archives of Osteoporosis

, 11:25 | Cite as

A systematic review of intervention thresholds based on FRAX

A report prepared for the National Osteoporosis Guideline Group and the International Osteoporosis Foundation
  • John A. KanisEmail author
  • Nicholas C. Harvey
  • Cyrus Cooper
  • Helena Johansson
  • Anders Odén
  • Eugene V. McCloskey
  • The Advisory Board of the National Osteoporosis Guideline Group



This systematic review identified assessment guidelines for osteoporosis that incorporate FRAX. The rationale for intervention thresholds is given in a minority of papers. Intervention thresholds (fixed or age-dependent) need to be country-specific.


In most assessment guidelines, treatment for osteoporosis is recommended in individuals with prior fragility fractures, especially fractures at spine and hip. However, for those without prior fractures, the intervention thresholds can be derived using different methods. The aim of this report was to undertake a systematic review of the available information on the use of FRAX® in assessment guidelines, in particular the setting of thresholds and their validation.


We identified 120 guidelines or academic papers that incorporated FRAX of which 38 provided no clear statement on how the fracture probabilities derived are to be used in decision-making in clinical practice. The remainder recommended a fixed intervention threshold (n = 58), most commonly as a component of more complex guidance (e.g. bone mineral density (BMD) thresholds) or an age-dependent threshold (n = 22). Two guidelines have adopted both age-dependent and fixed thresholds.


Fixed probability thresholds have ranged from 4 to 20 % for a major fracture and 1.3–5 % for hip fracture. More than one half (39) of the 58 publications identified utilised a threshold probability of 20 % for a major osteoporotic fracture, many of which also mention a hip fracture probability of 3 % as an alternative intervention threshold. In nearly all instances, no rationale is provided other than that this was the threshold used by the National Osteoporosis Foundation of the USA. Where undertaken, fixed probability thresholds have been determined from tests of discrimination (Hong Kong), health economic assessment (USA, Switzerland), to match the prevalence of osteoporosis (China) or to align with pre-existing guidelines or reimbursement criteria (Japan, Poland). Age-dependent intervention thresholds, first developed by the National Osteoporosis Guideline Group (NOGG), are based on the rationale that if a woman with a prior fragility fracture is eligible for treatment, then, at any given age, a man or woman with the same fracture probability but in the absence of a previous fracture (i.e. at the ‘fracture threshold’) should also be eligible. Under current NOGG guidelines, based on age-dependent probability thresholds, inequalities in access to therapy arise especially at older ages (≥70 years) depending on the presence or absence of a prior fracture. An alternative threshold using a hybrid model reduces this disparity.


The use of FRAX (fixed or age-dependent thresholds) as the gateway to assessment identifies individuals at high risk more effectively than the use of BMD. However, the setting of intervention thresholds needs to be country-specific.


Assessment guidelines Calibration Discrimination FRAX Intervention threshold 



American Association of Clinical Endocrinologists


American College of Rheumatology


Area under the receiver operating characteristic (ROC) curve


Bone mineral density


Body mass index


Canadian Association of Radiologists and Osteoporosis Canada


Confidence interval


Clinical risk factor


Dual-energy X-ray absorptiometry


European Calcified Tissue Society


European Federation of Pharmaceutical Industry Associations


European Society for Clinical and Economic Aspects of Osteoporosis


WHO fracture risk assessment tool.


Hip fracture


Hungarian Society for Osteoporosis and Osteoarthrology


International Osteoporosis Foundation


International Society of Clinical Densitometry


Japanese Society for Bone and Mineral Research


Major osteoporotic fracture


National Clinical Guideline Centre


National Clinical Guideline Centre


National Institute for health and Clinical Excellence


Number Needed to FRAX


Number needed to scan


National Osteoporosis Foundation, US


National Osteoporosis Foundation of South Africa


National Osteoporosis Guideline Group, UK


Net reclassification improvement (I)


Osteoporosis Self-Assessment Tool


Kuopio Osteoporosis Risk Factor and Prevention - study


US Preventive Services Task Force


Quality-adjusted life year


Quality-adjusted life year


A fracture risk assessment tool


Royal College of Physicians, London


Receiver operating characteristics


Screening of older women for prevention of fracture - study


Simple Calculated Osteoporosis Risk Estimation Tool


Standard deviation


Scottish Intercollegiate Guidelines Network


Società Italiana dell'Osteoporosi, del Metabolismo Minerale e delle Malattie dello Scheletro


Trabecular bone score


The Health Improvement Network


The number of SD units that BMD differs from the young healthy reference population


World Health Organization


Young adult mean values for BMD



We are grateful to the University of Southampton and the International Osteoporosis Foundation for their help with the literature searches. The manuscript was appraised by the members of the Committee of Scientific Advisors of the International Osteoporosis Foundation and the National Osteoporosis Guideline Group (UK) and we appreciate their constructive reviews. We are grateful to the International Osteoporosis Foundation and the National Osteoporosis Guideline Group for their endorsement of this paper.

Compliance with ethical standards

Conflicts of interest

Professor Kanis led the team that developed FRAX as director of the WHO Collaborating Centre for Metabolic Bone Diseases; he has no financial interest in FRAX. Professors McCloskey, Oden, Harvey and Dr Johansson are members of the FRAX team. Professors Cooper, Kanis, Harvey and McCloskey are members of the Advisory Board of the National Osteoporosis Guideline Group. Ken E Poole, Neil Gittoes and Sally Hope declare no competing interests with respect to this paper.

Funding source



Age-dependent threshold

Intervention or assessment threshold of fracture probability that varies with age

Assessment threshold

The fracture probability at which further assessment id recommended (usually BMD)

Fixed threshold

Intervention or assessment threshold of fracture probability that is fixed over all ages

Fracture threshold

The average probability of fracture for a specific age

Hybrid threshold

Intervention or assessment threshold of fracture probability that partly varies with age and is partly fixed

Intervention threshold

For this report, the fracture probability at which treatment is recommended

Major osteoporotic fracture

Fracture of hip, spine (clinical), distal forearm or humerus.

NOGG strategy

The strategy that describes intervention or assessment threshold of fracture probability that varies with age


In this report, BMD defined: a T-score of between −1 and −2.5


In this report, BMD defined: a T-score of <−2.5


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Copyright information

© International Osteoporosis Foundation and National Osteoporosis Foundation 2016

Authors and Affiliations

  • John A. Kanis
    • 1
    • 2
    Email author
  • Nicholas C. Harvey
    • 3
  • Cyrus Cooper
    • 3
  • Helena Johansson
    • 1
  • Anders Odén
    • 1
  • Eugene V. McCloskey
    • 1
  • The Advisory Board of the National Osteoporosis Guideline Group
  1. 1.Centre for Metabolic DiseasesUniversity of Sheffield Medical SchoolSheffieldUK
  2. 2.Institute of Health and AgeingAustralian Catholic UniversityMelbourneAustralia
  3. 3.MRC Lifecourse Epidemiology UnitUniversity of SouthamptonSouthamptonUK

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