Original ArticlesPrediction of fracture from low bone mineral density measurements overestimates risk
Introduction
Of the osteoporotic fractures that arise, the greatest morbidity and mortality is associated with hip fracture.23 Hip fracture also accounts for the greatest burden to health services in terms of direct costs, and to society in health economic terms.1, 21 Because bone mineral density (BMD) measurements aid in the prediction of hip fractures and other osteoporotic fractures,17 there has been a great deal of interest in the use of BMD measurements and other risk assessments to identify individuals at risk for fracture in the hope that interventions can be undertaken in the most cost-effective manner.
There have been many agents developed for clinical use that are capable of modulating bone mineral density in individuals with osteoporosis and, in many cases, the effects on bone mineral density have been shown to be associated with a significant decrease in the risk of osteoporotic fractures.14, 19 Most of these treatments have been given to relatively young women, often with an average age range of 50–65 years. The average age of hip fracture in many countries, however, is ≥80 years,5 15–30 years after most interventions are contemplated. Thus, most hip fractures are likely to occur 15–30 years after assessment of bone mineral density. For these reasons, it is important to assess the effects of risk assessment over a lifetime, rather than over a few years, in the natural history of osteoporosis. In an earlier study we showed that lifetime risk of fracture is underestimated when current trends in mortality are ignored.20 In this study we show that estimates of risk based on low BMD produced from relatively short-term studies overestimate the risk over the lifetime of patients.
Section snippets
Methods and assumptions
Bone mineral density at any given age is assumed to be normally distributed. The risk of hip fracture is presumed to increase by a constant fraction for each standard deviation decrease in bone mineral density. In this article we model apparent gradients of risk of 1.4- and 2.6-fold increases in risk for each standard deviation decrease in bone mineral density. The former approximates the lower estimates of the risk of hip fracture provided by single-photon absorptiometry at the forearm from
Results
The effect of time on correlation coefficients between two sets of BMD measurements is shown in Table 1 using observed coefficients ranging from 0.4 to 0.8. Over all ranges of assumptions and intervals, correlation coefficients are expected to decline with time. For example, where studies undertaken for 5 years show a correlation coefficient of 0.8, the true correlation coefficient 15 years later is likely to be 0.41. The effect is proportionately greater with poorer correlation coefficients.
Discussion
Current definitions of osteoporosis incorporate low bone mineral density as a cornerstone.2 Diagnostic criteria for osteoporosis have been developed based on the relationship of a given bone mineral density to that of the young, healthy population.23 The diagnosis of osteoporosis is only of relevance where it helps in deciding on management, or gives useful prognostic information. With regard to the latter, there are many prospective observational studies that have assessed the utility of bone
Acknowledgements
We are grateful to Lilly Research Centre for their support of this work.
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