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      FRAX™ and the assessment of fracture probability in men and women from the UK

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          Abstract

          Summary

          A fracture risk assessment tool (FRAX™) is developed based on the use of clinical risk factors with or without bone mineral density tests applied to the UK.

          Introduction

          The aim of this study was to apply an assessment tool for the prediction of fracture in men and women with the use of clinical risk factors (CRFs) for fracture with and without the use of femoral neck bone mineral density (BMD). The clinical risk factors, identified from previous meta-analyses, comprised body mass index (BMI, as a continuous variable), a prior history of fracture, a parental history of hip fracture, use of oral glucocorticoids, rheumatoid arthritis and other secondary causes of osteoporosis, current smoking, and alcohol intake 3 or more units daily.

          Methods

          Four models were constructed to compute fracture probabilities based on the epidemiology of fracture in the UK. The models comprised the ten-year probability of hip fracture, with and without femoral neck BMD, and the ten-year probability of a major osteoporotic fracture, with and without BMD. For each model fracture and death hazards were computed as continuous functions.

          Results

          Each clinical risk factor contributed to fracture probability. In the absence of BMD, hip fracture probability in women with a fixed BMI (25 kg/m 2) ranged from 0.2% at the age of 50 years for women without CRF’s to 22% at the age of 80 years with a parental history of hip fracture (approximately 100-fold range). In men, the probabilities were lower, as was the range (0.1 to 11% in the examples above). For a major osteoporotic fracture the probabilities ranged from 3.5% to 31% in women, and from 2.8% to 15% in men in the example above. The presence of one or more risk factors increased probabilities in an incremental manner. The differences in probabilities between men and women were comparable at any given T-score and age, except in the elderly where probabilities were higher in women than in men due to the higher mortality of the latter.

          Conclusion

          The models provide a framework which enhances the assessment of fracture risk in both men and women by the integration of clinical risk factors alone and/or in combination with BMD.

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          Most cited references85

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          Diagnosis of osteoporosis and assessment of fracture risk.

          John Kanis (2002)
          The diagnosis of osteoporosis centres on the assessment of bone mineral density (BMD). Osteoporosis is defined as a BMD 2.5 SD or more below the average value for premenopausal women (T score < -2.5 SD). Severe osteoporosis denotes osteoporosis in the presence of one or more fragility fractures. The same absolute value for BMD used in women can be used in men. The recommended site for diagnosis is the proximal femur with dual energy X-ray absorptiometry (DXA). Other sites and validated techniques, however, can be used for fracture prediction. Although hip fracture prediction with BMD alone is at least as good as blood pressure readings to predict stroke, the predictive value of BMD can be enhanced by use of other factors, such as biochemical indices of bone resorption and clinical risk factors. Clinical risk factors that contribute to fracture risk independently of BMD include age, previous fragility fracture, premature menopause, a family history of hip fracture, and the use of oral corticosteroids. In the absence of validated population screening strategies, a case finding strategy is recommended based on the finding of risk factors. Treatment should be considered in individuals subsequently shown to have a high fracture risk. Because of the many techniques available for fracture risk assessment, the 10-year probability of fracture is the desirable measurement to determine intervention thresholds. Many treatments can be provided cost-effectively to men and women if hip fracture probability over 10 years ranges from 2% to 10% dependent on age.
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            Predictive value of BMD for hip and other fractures.

            The relationship between BMD and fracture risk was estimated in a meta-analysis of data from 12 cohort studies of approximately 39,000 men and women. Low hip BMD was an important predictor of fracture risk. The prediction of hip fracture with hip BMD also depended on age and z score. The aim of this study was to quantify the relationship between BMD and fracture risk and examine the effect of age, sex, time since measurement, and initial BMD value. We studied 9891 men and 29,082 women from 12 cohorts comprising EVOS/EPOS, EPIDOS, OFELY, CaMos, Rochester, Sheffield, Rotterdam, Kuopio, DOES, Hiroshima, and 2 cohorts from Gothenburg. Cohorts were followed for up to 16.3 years and a total of 168,366 person-years. The effect of BMD on fracture risk was examined using a Poisson model in each cohort and each sex separately. Results of the different studies were then merged using weighted coefficients. BMD measurement at the femoral neck with DXA was a strong predictor of hip fractures both in men and women with a similar predictive ability. At the age of 65 years, risk ratio increased by 2.94 (95% CI = 2.02-4.27) in men and by 2.88 (95% CI = 2.31-3.59) in women for each SD decrease in BMD. However, the effect was dependent on age, with a significantly higher gradient of risk at age 50 years than at age 80 years. Although the gradient of hip fracture risk decreased with age, the absolute risk still rose markedly with age. For any fracture and for any osteoporotic fracture, the gradient of risk was lower than for hip fractures. At the age of 65 years, the risk of osteoporotic fractures increased in men by 1.41 per SD decrease in BMD (95% CI = 1.33-1.51) and in women by 1.38 per SD (95% CI = 1.28-1.48). In contrast with hip fracture risk, the gradient of risk increased with age. For the prediction of any osteoporotic fracture (and any fracture), there was a higher gradient of risk the lower the BMD. At a z score of -4 SD, the risk gradient was 2.10 per SD (95% CI = 1.63-2.71) and at a z score of -1 SD, the risk was 1.73 per SD (95% CI = 1.59-1.89) in men and women combined. A similar but less pronounced and nonsignificant effect was observed for hip fractures. Data for ultrasound and peripheral measurements were available from three cohorts. The predictive ability of these devices was somewhat less than that of DXA measurements at the femoral neck by age, sex, and BMD value. We conclude that BMD is a risk factor for fracture of substantial importance and is similar in both sexes. Its validation on an international basis permits its use in case finding strategies. Its use should, however, take account of the variations in predictive value with age and BMD.
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              Meta-analysis of how well measures of bone mineral density predict occurrence of osteoporotic fractures.

              To determine the ability of measurements of bone density in women to predict later fractures. Meta-analysis of prospective cohort studies published between 1985 and end of 1994 with a baseline measurement of bone density in women and subsequent follow up for fractures. For comparative purposes, we also reviewed case control studies of hip fractures published between 1990 and 1994. Eleven separate study populations with about 90,000 person years of observation time and over 2000 fractures. Relative risk of fracture for a decrease in bone mineral density of one standard deviation below age adjusted mean. All measuring sites had similar predictive abilities (relative risk 1.5 (95% confidence interval 1.4 to 1.6)) for decrease in bone mineral density except for measurement at spine for predicting vertebral fractures (relative risk 2.3 (1.9 to 2.8)) and measurement at hip for hip fractures (2.6 (2.0 to 3.5)). These results are in accordance with results of case-control studies. Predictive ability of decrease in bone mass was roughly similar to (or, for hip or spine measurements, better than) that of a 1 SD increase in blood pressure for stroke and better than a 1 SD increase in serum cholesterol concentration for cardiovascular disease. Measurements of bone mineral density can predict fracture risk but cannot identify individuals who will have a fracture. We do not recommend a programme of screening menopausal women for osteoporosis by measuring bone density.
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                Author and article information

                Contributors
                +44-114-2851109 , +44-114-2851813 , w.j.Pontefract@shef.ac.uk
                Journal
                Osteoporos Int
                Osteoporosis International
                Springer-Verlag (London )
                0937-941X
                1433-2965
                22 February 2008
                April 2008
                : 19
                : 4
                : 385-397
                Affiliations
                [1 ]WHO Collaborating Centre for Metabolic Bone Diseases, University of Sheffield Medical School, Beech Hill Road, Sheffield, S10 2RX UK
                [2 ]Department of Orthopaedics, Malmö General Hospital, Malmö, Sweden
                [3 ]Consulting Statistician, Gothenburg, Sweden
                [4 ]Osteoporosis Centre, Northern General Hospital, Sheffield, UK
                Article
                543
                10.1007/s00198-007-0543-5
                2267485
                18292978
                1cabe121-8832-4575-94f0-4e9540b9f3c5
                © International Osteoporosis Foundation and National Osteoporosis Foundation 2007
                History
                : 5 November 2007
                : 10 December 2007
                Categories
                Special Position Paper
                Custom metadata
                © International Osteoporosis Foundation and National Osteoporosis Foundation 2008

                Orthopedics
                clinical risk factors,osteoporotic fracture,frax™,fracture probability
                Orthopedics
                clinical risk factors, osteoporotic fracture, frax™, fracture probability

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