Original Full Length ArticleProbability of fractures predicted by FRAX® and observed incidence in the Spanish ECOSAP Study cohort
Highlights
► ECOSAP is a 3-year prospective study with fracture data from 5,201 Spanish women. ► FRAX® underestimated the risk of major osteoporotic fractures in the ECOSAP cohort. ► The estimated compared with the observed women with hip fractures were similar. ► Clinical judgment is needed to estimate the fracture risk in the individual patient.
Introduction
The ability to accurately gauge absolute fracture risk is crucial for implementing preventive measures, making clinical decisions in the individual patient as well as for identifying cost-effective thresholds for pharmacological intervention. This approach has previously been introduced in highly prevalent diseases such as cardiovascular diseases, stroke, and breast cancer [1], [2], [3]. The WHO Collaborating Center for Metabolic Bone Diseases at Sheffield has recently developed algorithms to compute age-specific fracture probabilities in men and women from clinical risk factors (CRFs) and bone mineral density (BMD) measurements at the femoral neck. The algorithms (FRAX®) are based on a series of analyses using the primary data from large population-based cohorts that have identified several CRFs for fracture. The performance characteristics of CRFs have been validated in independent, population-based prospectively studied cohorts with over a million person-years of observation [4]. The FRAX® tools calculate the 10-year probability of a major osteoporotic fracture (clinical spine, hip, forearm or proximal humerus) and hip fracture adjusted to the fracture and death hazards of several countries, including Spain [4]. However, there were no Spanish population-based cohorts included in the meta-analysis for the development of the FRAX® algorithm. Moreover, it has been assumed that the Spanish algorithm for the 10-year major osteoporotic fracture prediction is robust enough to be rolled out for clinical use and development of treatment guidelines. This may not be necessarily correct, since the rate of major osteoporotic fractures in the Spanish version of FRAX® was derived by extrapolation from the ratio of hip fractures/major osteoporotic fractures in Sweden (Malmö) [5], and not from country-specific studies that were not available at the time the Spanish algorithm was developed. Therefore, it is important to look for additional independent cohorts in which the country-specific predictions from FRAX® can be objectively tested.
The ECOSAP (Ecografía Osea en Atención Primaria) Study, the largest epidemiological, prospective fracture study performed in Spain to date, was a 3-year, prospective study to test the ability of calcaneal quantitative ultrasound (QUS) and several clinical risk factors, including those used in the FRAX® tool, of osteoporosis and fractures to predict the non-vertebral fracture risk in 5201 postmenopausal women in Spain [6].
To evaluate the ability of the Spanish algorithm of FRAX®, we compared calculated FRAX® predicted probabilities of hip and major osteoporotic fractures to the actual fracture incidence observed in the ECOSAP Study cohort.
Section snippets
Patients and methods
The details of the study cohort and assessment methods have been previously published [6]. The study comprised a total of 5201 Caucasian women aged 65 or older, recruited in 58 primary care centers of the National Health Service (NHS) throughout Spain between March 2000 and June 2001, regardless of the reason for consultation. An average of 90 women was included in each study site (range: 26 to161). A non-randomized sampling of consecutive cases attending the study sites was carried out, though
Results
Table 1 shows the baseline characteristics of the risk factors of the FRAX® tool in the ECOSAP Study cohort. A more comprehensive description of the baseline characteristics of the cohort is available in the publication of the primary study results [6], [7]. One hundred (1.9%) women died during a median of 36.1 months follow-up [10]. The mean (SD) FRAX® calculated 10-year probabilities for having a major osteoporotic fracture and a hip fracture were 8.78% (5.93%) and 3.67% (4.45%) respectively.
Discussion
According to our results regarding the ECOSAP cohort of postmenopausal women who were attended in primary care centers throughout Spain, the application of the FRAX® tools calibrated for Spain underestimates the risk of major osteoporotic fractures, especially in the lower fracture risk groups. In contrast, the number of estimated hip fractures compared with those observed was very similar, although the ability to discriminate at the individual case level was modest, as shown by the low area
Funding
This study was supported by an unrestrictive research grant from the Medical Research Department, Eli Lilly and Company. Madrid. Spain.
Disclosure statement
F.M. is an employee of Lilly, a company that investigates and commercializes bone active drugs. All other authors state that they have no conflicts of interest.
Acknowledgments
We are indebted to the women who participated in the study. We thank Sergi Mojal, Institut Municipal d'Investigació Mèdica (IMIM), for statistics programming, and to Helena Johansson, WHO Collaborating Center, for the calculation of the individual patients' absolute fracture risks. The list of ECOSAP investigators has been previously published [6].
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