A systematic review of intervention thresholds based on FRAX: A report prepared for the National Osteoporosis Guideline Group and the International Osteoporosis Foundation

Summary 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. Introduction 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. Methods 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. Results 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. Conclusion 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

Case finding for the management of osteoporosis with FRAX--assessment and intervention thresholds for the UK

SUMMARY: Assessment and intervention thresholds are developed and proposed in men aged over 50 years and postmenopausal women for the UK based on fracture probability from the WHO fracture risk assessment tool (FRAX). INTRODUCTION: The FRAX tool has recently become available to compute the 10-year probability of fractures in men and women from clinical risk factors (CRFs) with or without the measurement of femoral neck bone mineral density (BMD). The aim of this study was to develop a case-finding strategy for men and women from the UK at high risk of osteoporotic fracture by delineating the fracture probabilities at which BMD testing or intervention should be recommended. METHODS: Fracture probabilities were computed using the FRAX tool calibrated to the epidemiology of fracture and death in the UK. The relationship between cost effectiveness and fracture probability used the source data from a prior publication that examined the cost effectiveness of generic alendronate in the UK. An intervention threshold was set by age in men and women, based on the fracture probability equivalent to that of women with a history of a prior osteoporosis related fracture. In addition, assessment thresholds for the use of BMD testing were explored. Assessment thresholds for the measurement of BMD followed current practice guidelines where individuals were considered to be eligible for assessment in the presence of one or more CRF. An upper assessment threshold (i.e. a fracture probability above which patients could be treated without recourse to BMD) was based on optimisation of the positive predictive value of the assessment tool. The consequences of assessment and intervention thresholds on the requirement for BMD test and interventions were assessed using the distribution of clinical risk factors and femoral neck BMD for women in the source cohorts used for the development of the FRAX models RESULTS: Treatment was cost effective at all ages when the 10-year probability of a major fracture exceeded 7%. The intervention threshold at the age of 50 years corresponded to a 10-year probability of a major osteoporotic fracture of 7.5%. This rose progressively with age to 30% at the age of 80 years, so that intervention was cost effective at all ages. Assessment thresholds for testing with BMD (6-9% at the age of 50 years) also rose with age (18-36% at the age of 80 years). The use of these thresholds in a case-finding strategy would identify 6-20% of women as eligible for BMD testing and 23-46% as eligible for treatment, depending on age. The same threshold can be used in men. CONCLUSION: The study provides a method of developing management algorithms for osteoporosis from the estimation of fracture probabilities, rather than those based on BMD alone or BMD with single or multiple CRF