Author's response to reviews

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1 Author's response to reviews Title:The discriminative ability of FRAX, the WHO algorithm, to identify women Authors: Abdellah El Maghraoui Siham Sadni Nabil Jbili Asmaa Rezqi Aziza Mounach Imad Ghozlani Version:3Date:15 July 2014 Author's response to reviews: see over

2 Response to reviewers: Title: The discriminative ability of FRAX, the WHO algorithm, to identify women with prevalent asymptomatic vertebral fractures: a cross-sectional study. Authors: A. El Maghraoui, S. Sadni, N. Jbili, A. Rezqi, A. Mounach, I. Ghozlani. Version 2: date 15 july 2014 Author s response to reviewers: see over

3 Reviewer's report Title: The discriminative ability of FRAX, the WHO algorithm, to identify women Version:2 Date:29 June 2014 Reviewer:Ole Rintek R Madsen Reviewer's report A well-written, easy to follow paper regarding the discriminative ability of FRAX to identify women with prevalent asymptomatic vertebral fractures (grade 1, 2 and 3). We thank the reviewer for his comments Major compulsory revisions I would suggest to add risk to FRAX (FRAX risk) when the authors actually refer to FRAX risk (and not just to FRAX). For example, in the conclusion: The FRAX for major fracture without BMD had a better discriminative capacity... should be FRAX risk for major... This was added as suggested. Results and conclusion. Results for grade 1 vertebral fractures (AUC, sensitivity, specificity) should also be presented in the paper. If the conclusion of this paper only refers to grade 2 and 3 fractures, this should be specified. Results of AUC for grade 1 VFs were added as suggested. It is concluded that the FRAX for major fracture without BMD had a better discriminative capacity in identifying the women with prevalent asymptomatic VFs than lumbar spine and femoral neck T-scores. As far as I can see, this was only proven for spinal T-scores (p-value , page 7; p-value for femoral neck T-score not shown anywhere in the manuscript). P-values regarding differences between the different AUC-values should be given in Table 2. Comparison between the ROC curves was added as suggested. If FRAX was not a statistically significantly better discriminator than femoral neck T-score, the conclusion should be modified. The difference was statistically significant. Methods: VFA was used to identify vertebral fractures. The authors should discuss the reliability of this method compared to plain x-rays. The Genant method was used to grade the fractures but this method is based on X-rays examinations. Please, discuss the potential limitations of this approach. We added a paragraph on VFA and its strengths and limitations in the introduction chapter. Statistics: The aim of the study was to describe the performance of the FRAX tool as a diagnostic test. Consequently, positive and negative predictive values should be calculated instead of or in

4 addition to sensitivity and specificity. The sensitivity is the probability of a positive test GIVEN that the disease is present. Obviously, in the present context it is far more relevant to know the probability that the disease is present when the test is positive (positive predictive value). Alternatively, positive and negative likelihood ratios could be used as they do not depend on prevalence. ROC-curves are appropriate as such but do not have a direct interpretation usable for the clinician. We added in table 3 the positive and negative predictive values and positive likelihood ratios with the corresponding cut-offs of lumbar spine and femoral neck T-scores and FRAX major fracture model without BMD for the prediction of grade 2/3 vertebral fractures. Discussion. Please, discuss why the finding of the study has any interest at all: FRAX had a better discriminative capacity in identifying the women with prevalent asymptomatic VFs than T-scores. If you suspect that the patient may have an asymptomatic VF, why not just perform a VFA or a plain X-ray and get a final answer? After all, the FRAX result can only be used as an indicator of fracture (although it may be superior to T-scores). The problem is: how to suspect that a patient has an asymptomatic fracture? The classical sign of height loss lack accuracy and specificity. Thus, regarding the important health consequences of osteoporotic VFs, together with the fact that most of them are undiagnosed, emphasizes the need for developing better methods to identify patients with asymptomatic VFs. Table 1: ALL risk factors included in the FRAX algorithm (and used by the authors to calculate the FRAX risks) should be given in the Table. ALL risk factors with a value different from 0 are in table 1. None of the women were smoking or drinking alcohol (due to cultural reasons). Due to our inclusion criteria, none of our patients had a secondary osteoporosis or were taking steroids. Table 3: As AUC for femoral neck T-scores was numerically higher than for spinal T-scores, it is unclear why sensitivity and specificity are shown for spinal T-scores but not for femoral neck T-scores. In order to make the table easier to understand, % should be added to each of the cut-off values for FRAX major fractures without BMD (column far left in the table) Table 3 was revised as suggested. Level of interest: An article of importance in its field Quality of written English: Acceptable Statistical review: No, the manuscript does not need to be seen by a statistician. Declaration of competing interests: I declare that I have no competing interests

5 Reviewer 2: Reviewer's report Title: The discriminative ability of FRAX, the WHO algorithm, to identify women Version: 2 Date: 1 July 2014 Reviewer: Antonino Catalano Reviewer's report: This is an interesting cross-sectional study aimed to evaluate the relationship between FRAX score and the prevalence of asymptomatic vertebral fractures in a large sample of Moroccan postmenopausal women. The Authors found that FRAX score with or without BMD is predictive of prevalent vertebral fractures. Their conclusions indicate that FRAX for major fracture without BMD discriminates women with vertebral fractures better than T-score obtained with DXA assessment at lumbar spine or femoral neck. We thank the reviewer for his comments Discretionary Revisions. Some questions rise from this manuscript. In the methods section, treatment with corticosteroids was considered an exclusion criterion: because use of systemic glucocorticoids is a dichotomous risk factor useful to estimate FRAX score, Authors should justify why they decided to exclude women taking steroids. The same could be said for secondary osteoporosis. Further studies are needed to extend these results to the general population. The main objective of the study was to assess the prevalence and risk factors of vertebral fractures in a cohort of asymptomatic postmenopausal women. In this study, we aimed to assess the discriminative ability of FRAX in identifying the women with prevalent asymptomatic vertebral fractures. It should be specified if the clinician assigned to vertebral fractures assessment was blinded to patient clinical data. This was specified as suggested. Moreover, assessment of vertebral fractures was limited to T4-L4 and not all the women had an extensive vertebral evaluation. We added a paragraph on VFA and its strengths and limitations in the introduction chapter. Although these limitations, the manuscript is well carried out and suggest the use of FRAX tool to select women for vertebral fracture assessment. Level of interest: An article of importance in its field Quality of written English: Acceptable Statistical review: No, the manuscript does not need to be seen by a statistician. Declaration of competing interests: I declare that I have no competing interests