According to the comparative analysis of the baseline characteristics between the participants and the non participants for any reason we found that the non participants did not differ from the participants except in that they were one year older and more patients were on glucocorticoids. Thus, the participants in the study did not present worst conditions of the cohort.
Self-reported generally even structured interview have a significant correlation with those in the medical record. In any case always been found documented as explained. In all cases of fracture the medical records of the patients were reviewed and, when necessary, we requested a medical report for its validation. All cases of fracture that could not be verified or those arising from a motor vehicle accident or major trauma were excluded from analysis, fractures in the history of the subjects under study. A potential limitation of self-reported fractures is in vertebral fractures. In our study the total self-reported fractures were 16% higher than they were registered and so were excluded from the final analysis. It can be an advantage for risk predictions proposed by FRAX.
The present study is centered on the discriminatory and predictive capacity of the FRAX. Analysis of the AUC-ROC was used to analyse the discriminatory capacity of this tool. As shown in (Table
4) the results of the FRAX without DXA values were greater than the AUC-ROC of BMD with values of the T-score of the femoral neck. Thus, these results demonstrate that the FRAX without the determination of BMD presents a discriminatory capacity not inferior to and even somewhat better than the DXA, according to the AUC-ROC. Analysis of the BMD with the DXA technique for the axial skeleton has traditionally been considered as the best predictive test known to determine fragility fractures
[9, 26, 36] with the strategy of intervention for their prevention in medical practice having been based on this test in Spain
 and in the remainder of the international scientific community until the appearance of the importance of other risk factors for fracture
On analysing the role of the determination of BMD of L1-L4 in the different tests, it was found that the discriminatory capacity for major fracture using the AUC- ROC was lower than that of the determination of BMD with the T-score of the femoral neck, although statistical significance was maintained (Table
4). This inferiority was maintained for hip fracture but with no significant differences since the confidence interval integrates the value 0.50 which is the value of statistical significance for this test. Part of the debate on the possible weaknesses of the FRAX has been centered on the lack of the BMD values of the lumbar spine in its algorithm. This criticism is based on the traditional consideration that the BMD of each area presents the best predictive capacity for fractures in the same area, especially for the vertebrae and the hip
 and, thus, it has been argued that the prediction of vertebral fractures could be improved. The discriminatory capacity measured with the AUC-ROC worsened with the incorporation of the L1-L4 T-score in the algorithm of the FRAX for major or hip fractures (Table
4). This result is congruent, but on introducing the L1-L4 T-score value in the FRAX (as a simulation) to analyse what would happen with vertebral fracture, the result of the AUC-ROC for vertebral fracture worsened slightly with respect to that obtained with the FN T-score, although without significant differences. Thus, on introducing the values of the L1-L4 T-score in the FRAX in this study the result did not provide an improvement in the discrimination of vertebral fractures measured with the AUC-ROC. Although it has described that a correction can adapt the lumbar spine BMD and improve the prediction for major and vertebral fractures of FRAX
 in our study by incorporating the lumbar spine BMD did not improve the discriminative ability of FRAX measured by AUC with femoral neck BMD neither for major or vertebral fracture (data not showed).
The adjusted predictive capacity of the FRAX analysed using the ObsFx/ExpFx ratio was far from the 1 value which would be the desired result in the case of good adjustment of the predictive capacity of the FRAX in our country. In our cohort this ratio was of 2.4 for major fracture and 2.8 for hip fracture. These values improved minimally on the introduction of the T-score of the femoral neck in the algorithm (2.2 and 2.3 respectively). Indeed, the FRAX predicted the risk of major fracture in 41.1% of the women and 35.5% for hip fracture without BMD, with these values improving only slightly with 46% and 42.8%, respectively on performing the BMD with DXA.
These data seem to coincide with the analysis recently carried out in two cohorts of French women with a similar overall discriminatory value for fracture and low overall sensitivity (48-50% for FRAX predictions) and better than BMD alone
[33, 37]. In Spain our group previously demonstrated that the FRAX has good capacity to detect densitometric osteoporosis but also with imbalance in the predictive capacity
[38–40]. Nonetheless, a two recent studies in Spain had shown similar results to ours for major fractures with an ObsFx/ExpFx ratio of 3.1 (CI 95%: 2.8-3.5) and 0.8 (CI 95%: 0.7-1.1) for hip fracture
. Although the initial formation of the two cohorts followed very similar schemes, the method of follow up in our study was notably different. In the present study we only analysed fragility fractures reported by the women, which could be contrasted with electronic record or clinical reports. In the second study the results of ratio ObsFx/ExpFx were 0.66 and 1.10 for major and hip fracture respectively
. The most important methodological differences were that the study was carry out for a three years period, the authors do not included vertebral fractures
The ROC curve has several problems. For analysis of sensitivity and specificity we have not a gold standard of FRAX for Spanish population. Moreover, ROC needs a gold standard of illness (fracture) and we do not have because of the electronic records are not completely reliable and we needed to make a double check (self-reported validate against records). On the other hand, the area under the ROC curve is important, since it measures the discrimination power of the model. Nevertheless, tests of discrimination alone are not sufficient for model evaluation, since they do not indicate whether calibration is also good
[34, 35, 42].
In our study, on application of the Hosmer-Lemeshow test a good correlation was observed between the different quintiles of risk in all the simulation (Figures
5) but with a line which groups the results of the regression deviated from the reference toward the values observed. This circumstance led us to carry out a calibration multiplying each of the values resulting from the prediction made by the FRAX by a constant based on the ObsFx/ExpFx ratio for major fracture and for hip fracture. As shown in the lower part (calibration) of Figures
5, on multiplication of the results of the FRAX by the ObsFx/ExpFx ratios, the results with their CI 95% adjust perfectly to the diagonal of reference in the Hosmer-Lemeshow test.
The FRAX tool can therefore be considered to present with a poor discriminatory capacity for women to have major osteoporotic fractures within 10 years, with this capacity being good for hip fractures without the need of determining the BMD, although this improves somewhat with its determination. The FRAX tool shows a scarce predictive capacity of the risk of fracture and predicts less than 50% of those which occur. The reason for this underdiagnosis may be because the Spanish cohort introduced as the reference in the FRAX tool is not representative of the current female population since these women present significantly more fractures than those actually predicted by the FRAX tool.
We have excluded from the analysis of the cohort of women receiving active treatment for the bone at baseline of the study because of the FRAX has so defined, but we have not been excluded women who received treatment during the 10-year period. This can be a potential confounding factor, however exclude women would mean removing the greatest potential for fracture, but keep going who have received treatment can be reduced the all risk of new fractures observed. Other potential confounding factor can be the Calcium/Vit D supplement intake because we have not excluded at baseline or during the study period. There is important discussion in the literature about the role of these supplements in reducing the risk of fracture, except in a subgroup of patients taking bone active drugs for the potential hypocalcaemia or in patients admitted to nursing homes. These patients are not included in this study. Moreover there is no significant difference between Calcium/Vit D supplement intake between participants and no participants.
New epidemiological studies are needed in our country to compare these results on major and other fragility fractures which, although not severe, also affect the quality of life
. However, together with other authors in our country
[6, 10, 34, 38–41] we believe that there are sufficient data to promote the habit of investigating the risk factors of fragility fracture among Spanish physicians, especially in primary care, to determine the absolute risk and be able to propose changes in lifestyle in persons with a high risk as well as evaluate which patients should be referred for determination of the BMD by DXA
. In our opinion, the current state of the FRAX needs some adjustments such as those proposed in this study. Something similar to this need for adaptation and adjustments happened in Spain with the application of the first Framingham-type cardiovascular risk scales which required adaptations such as the REGICOR scale and others in our country
We know that the promoters of the FRAX are committed to the adaptation of the tool to the different countries with the publication of new studies such as what has been done up to now. We also consider that with improvements this may be a very useful tool especially in the first level of care and this has been demonstrated by the important extension in its use worldwide