One Season in Professional Cycling Is Enough to Negatively Affect Bone Health
, Pedro E. Alcaraz 1, Raquel Ortolano-Ríos 2 and Cristian Marín-Pagán 1
Round 1
Reviewer 1 Report (Previous Reviewer 3)
The Authors accepted and followed my comments and suggestions except for the following 2 comments. Please, revise the manuscript by considering these two ones as well:
Discussion - Considering, that in osteopenia the BMD is between >1.0 and <2.5 SD 170 compared to the BMD of healthy young people at peak bone mass, and osteoporosis occurs when BMD is >2.5 SD compared to the BMD of healthy young people at peak bone 172 mass [29].” – this sentence is still not correct. The expression of T-score of BMD was correct, but -1 SD, -2,5SD values are suggested as cut-off values and not +1 SD and +2,5 SD values, please correct the sentence again.
Table 2 – it should be indicated what t-score and z-score exactly represent, i.e. t-score and z-score of total BMD? Not the explanation of z-score and t-score was missing from the table, only the studied variable.
Author Response
We thank the reviewer for their constructive and helpful feedback on our manuscript. We have replied to each specific comment in the section below and have introduced the corresponding edits in the manuscript using Word’s track changes.
Major Comments:
Discussion - Considering, that in osteopenia the BMD is between >1.0 and <2.5 SD 170 compared to the BMD of healthy young people at peak bone mass, and osteoporosis occurs when BMD is >2.5 SD compared to the BMD of healthy young people at peak bone 172 mass [29].” – this sentence is still not correct. The expression of T-score of BMD was correct, but -1 SD, -2,5SD values are suggested as cut-off values and not +1 SD and +2,5 SD values, please correct the sentence again.
Response: Thanks you for your comment. Following your suggestions, we have modified these expressions. Line 170.
Table 2 – it should be indicated what t-score and z-score exactly represent, i.e. t-score and z-score of total BMD? Not the explanation of z-score and t-score was missing from the table, only the studied variable.
Response: Following your suggestion, we have introduced new text to give more clarity to the variables T-score and Z-score.
Author comment: We appreciate all the comments made on our manuscript, which helped improve it’s quality.
We thank the reviewer for their constructive and helpful feedback on our manuscript. We have replied to each specific comment in the section below and have introduced the corresponding edits in the manuscript using Word’s track changes.
Major Comments:
Discussion - Considering, that in osteopenia the BMD is between >1.0 and <2.5 SD 170 compared to the BMD of healthy young people at peak bone mass, and osteoporosis occurs when BMD is >2.5 SD compared to the BMD of healthy young people at peak bone 172 mass [29].” – this sentence is still not correct. The expression of T-score of BMD was correct, but -1 SD, -2,5SD values are suggested as cut-off values and not +1 SD and +2,5 SD values, please correct the sentence again.
Response: Thanks you for your comment. Following your suggestions, we have modified these expressions. Line 170.
Table 2 – it should be indicated what t-score and z-score exactly represent, i.e. t-score and z-score of total BMD? Not the explanation of z-score and t-score was missing from the table, only the studied variable.
Response: Following your suggestion, we have introduced new text to give more clarity to the variables T-score and Z-score.
Author comment: We appreciate all the comments made on our manuscript, which helped improve it’s quality.
We thank the reviewer for their constructive and helpful feedback on our manuscript. We have replied to each specific comment in the section below and have introduced the corresponding edits in the manuscript using Word’s track changes.
Major Comments:
Discussion - Considering, that in osteopenia the BMD is between >1.0 and <2.5 SD 170 compared to the BMD of healthy young people at peak bone mass, and osteoporosis occurs when BMD is >2.5 SD compared to the BMD of healthy young people at peak bone 172 mass [29].” – this sentence is still not correct. The expression of T-score of BMD was correct, but -1 SD, -2,5SD values are suggested as cut-off values and not +1 SD and +2,5 SD values, please correct the sentence again.
Response: Thanks you for your comment. Following your suggestions, we have modified these expressions. Line 170.
Table 2 – it should be indicated what t-score and z-score exactly represent, i.e. t-score and z-score of total BMD? Not the explanation of z-score and t-score was missing from the table, only the studied variable.
Response: Following your suggestion, we have introduced new text to give more clarity to the variables T-score and Z-score.
Author comment: We appreciate all the comments made on our manuscript, which helped improve it’s quality.
Author Response File: 
Author Response.docx
Reviewer 2 Report (New Reviewer)
Dear authors,
the reviewer enjoyed reading your work. In fact we believe, if your results withstand all methodical issues, it could be of great benefit to sports-medical practitioners. Your publication is easy to read and understand. However, in order to be able to accept this work we need one major addition to the methodical part.
Line 35: It would be helpful if the authors would add here a short intro about weight management in professional cyclists. Reduced weight might generate an advantage in competition but ultimately negatively affect bone health. (You included some of this in your discussion in line 189 - but maybe you could add one sentence into the introduction.)
Line 94: What is the minimal detectable change of the used DXA (XR-46; Norland Corp., 95 Fort Atkinson, WI) for the parameters you measured? What is the technical error of this device? Looking at the results changes in BMD vary between 1-5% still being stated as statistically significant. However, we doubt that the system is actually capable of measure in such detail. To exclude statistical variance and prove us wrong, the authors need to determine and state (as stated by the DXA developers) the ability to differentiate on such a scale for every parameter used (minimal detectable change).
If you are able to solve these questions, we will be happy to accept your manuscript.
Thank you for your great efforts.
Author Response
The reviewer enjoyed reading your work. In fact we believe, if your results withstand all methodical issues, it could be of great benefit to sports-medical practitioners. Your publication is easy to read and understand. However, in order to be able to accept this work we need one major addition to the methodical part.
Response: We thank the reviewer for their constructive and helpful feedback on our manuscript. We have replied to each specific comment in the section below and have introduced the corresponding edits in the manuscript using Word’s track changes.
Line 35: It would be helpful if the authors would add here a short intro about weight management in professional cyclists. Reduced weight might generate an advantage in competition but ultimately negatively affect bone health. (You included some of this in your discussion in line 189 - but maybe you could add one sentence into the introduction.)
Response: Following your suggestion, we have added a new sentences in line 35.
Line 94: What is the minimal detectable change of the used DXA (XR-46; Norland Corp., 95 Fort Atkinson, WI) for the parameters you measured? What is the technical error of this device? Looking at the results changes in BMD vary between 1-5% still being stated as statistically significant. However, we doubt that the system is actually capable of measure in such detail. To exclude statistical variance and prove us wrong, the authors need to determine and state (as stated by the DXA developers) the ability to differentiate on such a scale for every parameter used (minimal detectable change).
Response: Thank you for your comment, in the methodology section under 2.3. where the DXA methodology is described, it is described that the coefficient of variation of the BMD measurements were 0.86% for the whole body. The anatomical segments of the arms, legs, trunk, ribs, pelvis and spine were analyzed using the whole-body scanner.
Differences in two serial assessments of a patient that are close in value could simply be due to random variation. To have 95% confidence (p<0.05) that a change in value represents a change in actual BMD, Norland applies a valid equation for two scans of the same anatomical site on a patient in the same Norland unit.
The detailed specifications of the whole-body scanner in the Norland manual are as follows:
- BMC CV: head, trunk, abdomen, arms, legs and total are 1.5%, 1.2%, 2.3%, 1.8%, 1.1% and 0.67%, respectively.
- BMD CV: head, trunk, abdomen, arms, legs and total are 1.6%, 2.1%, 2.3%, 1.6%, 1.3% and 0.78%, respectively.
- AREA CV: head, trunk, abdomen, arms, legs and total are 1.2%, 1.4%, 2%, 1.6%, 1.0% and 0.66%, respectively.
In addition, the manual indicates that the accuracy is typically within 2.0% of industry standard.
Within the manual we cannot find the minimum detectable change, if you could tell us where to find it we would appreciate it.
Author comment: We appreciate all the comments made on our manuscript, which helped improve it’s quality.
Author Response File: Author Response.docx
This manuscript is a resubmission of an earlier submission. The following is a list of the peer review reports and author responses from that submission.
Round 1
Reviewer 1 Report
Review of the manuscript: One season in professional cycling is enough to negatively affect bone health
The study aimed to assess how professional cycling affects bone health markers after one season. Authors concluded that after one season at the professional level, cyclists decreased BMD in the legs, trunk, ribs and pelvis. BMC decreased in the arms and spine. BA decreased in the arms and spine. In addition, a decrease in Z-score and a decreasing trend in T-score and total BMD were observed. One season of professional cycling is enough to negatively affect bone health status. It was an interesting paper. The topic of the present study is relevant for sport science. However, I have comments that need clarification.
Major Comments:
Introduction: The authors pointed that “These energy imbalances are related to reproductive function and bone health in female and male athletes, also known as the "Relative Energy Deficiency in Sport" (RED-S) [10]. Energy deficit-related suppression of hormones, such as testosterone, triiodothyronine (T3) and leptin, suggests dysregulation of the reproductive system and energy metabolism in male athletes [11, 12]”. For what purpose is there content here about REDS syndrome (which is not only about energy deficit) when this was not the subject of the study? Similarly, the paragraph about hormones, testosterone, triiodothyronine (T3) and leptin-is not relevant to what the authors analysed. The introduction should convince you why the specifics of cyclists' training affect bones. There is very little about this.
Material and Methods: Selection of participants - described quite clearly. Information important for densitometry data needs to be completed - ethnic group is Caucasian? Asian? Hispanic? Other researchers will then have complete information as BMD varies between ethnic groups, the reference base also varies. However, it should be stated whether bone-specific exclusion criteria such as rickets, metabolic diseases experienced in childhood, thyroid diseases where we know that these are confounding variables were applied. Were men with nutritional disorders excluded ? This is important. The description of the densitometric study needs to be completed what the standard error of measurement was, and between pre and post measurements. In section 2.3. you need to state the BMD of which bones were measured? Spine its lumbar or all?? BMD Legs its total? Or hip?? This was only given in the tables. The authors state in Table 2 that the variable was BMD of the legs (was lateralization given? was the non-dominant leg tested? average of both legs? BMD arms its mean from left and right? Authors pointed that one of the following criteria was aged (20 to 40 years). It is well known that age affects BMD. Have statistical methods checked whether it was age that correlated more strongly with BMD? Metric age (in this study there were athletes in their twenties as well as twice their age) in many good bone health studies is often a confounding variable.
Results: The results are shown clearly. However, the tables need to state whether the BMD Legs are the average of the left and right leg measurements? Why are BMD not given separately for each limb ? similarly arms. In table 2 last two line : T-score and Z-score are these average values from all measurements? In line 123 “Z-SCORE (-502%; p=0.021; 123 ES=0.556)” whether really -502% ???
The authors use the term "osteopenia" in describing the results , previously it was not explained what criteria was used for osteopenia or based on T-score? Z -score? classification is only in discussion lines 161-163
Discussion: The discussion lacks the limitations of the study. Given the small sample size, the lack of analysis of important determinants of BMD such as diet, supplementation, bone turnover markers, strength levels and many others such a section as limitations needs to be well described. Elite cyclists were investigated but the limitations of the study are significant.
Minor points:
The entire manuscript is worth reading again carefully. Ensure that the analyzed literature items are consistent with the area of your own research.
The manuscript needs minor technical and stylistic corrections. Large disproportion of the introduction chapters compared to the discussion.
Reviewer 2 Report
Dear Authors,
I hope you are doing very well.
The paper is currently in a good shape, congratulations. However, there are some methodological issues that concerns me. For that reason, I recommended major revisions. Please, see the document attached.
Kind regards
Comments for author File: 
Comments.pdf
Reviewer 3 Report
General remarks
The paper represents an effort to analyse one-year changes in bone health and body composition of professional cyclists. The topic of the manuscript is of high importance, since the training load of athletes may have significant influence on their bone structure. However, it was not clear why the studied year was special for the studied cyclists. They had been following the active lifestyle of professional athletes for ages, maybe for a longer period than a decade before the examination, it is not evident that only the cycling season resulted in their BMD, BMC and BA decrease. I recommend accepting this paper for publication in Nutrition after a major revision, because of the followings:
(1) My suggestion is to give an exact explanation why a one-year long interval in cyclist at the age of 25-30 years was critical in their activity.
(2) At the same time, I suggest to present the individual changes between 2018 and 2019 (in graphs like Fig. 1), because of 2 reasons: (a) in this form the analysis lost the longitudinal type of the raw data (there are individual changes between 2018 and 2019), (b) the trend of the changes could be more precisely described.
Minor remarks and suggestions
2.1. Selection of participants section – all of the subjects were male cyclists? Please indicate it in the text.
Results
Page 6 – “In addition, a significant decrease in BMC (p=<0.05; Figure 2) and BA (p=<0.05; Figure 106 3) were found in the arms” – by considering Fig 1, BMC in the arms increased and not decreased, please correct the text.
Discussion
Page 12 – “The WHO classifications for the diagnosis of osteopenia is a T-score value >1.0 to <2.5 SD, whereas for osteoporosis the T-score cutoff is ≥2.5 SD below the young adult mean …” – this statement should be corrected, negative values are in the classifications -1.0, -2.5 SD values are the cut-off values).
Page 13 – “Exercise is not responsible for menstrual dysfunction in female athletes [34]. However, there may be a genetic factor that makes some female athletes more at risk for functional hypothalamic amenorrhea (FHA) …” – the Authors referred only two articles, however, there are dozens of articles stating the contrary of these statements (i.e. excessive physical activity can harm the hypothalamo-hypophyseal-gonad axis and can result in menstruation abnormalities in females; it is not evidenced yet that only genetically prone females are recruited for sports with excessive physical load). These statements should be corrected, completed or deleted.
Page 13 – “In addition, it has recently been reported that serum cortisol concentration increased steadily after exercise relative to pre-exercise after 4 days of cycling training (3 h daily) …” – this cannot be a reason why cyclists have lower BMD than athletes from other sports, since the level of cortisol is elevated in them after exercise as well. This description of the relationship of worse bone health parameters with elevated cortisol level should be revised in the manuscript.
Page 13 – “At the metabolic level, an increase in sweat Ca+ loss during 2 h of moderate cycling has also been observed to be associated with a decrease in serum Ca+ accompanied by an increase in plasma parathyroid hormone concentration, which may promote bone resorption …” – all the studied subjects were professional athletes, it is not clear why Ca++ loss emerged as a nutritional problem in this sample. Professional athletes pay attention to their nutrition and vitamin and mineral supplementation. My suggestion is to give details on their vitamin and mineral supplementation too, if the Authors have data on these details, or leave out Ca++ loss from the possible influencing factors.
Table 1. if the dimension of FM and FFM gram, their values are not correct, please correct the data!
Table 1 – there is not BMI values in the Table body, but the abbreviation mentions BMI, please correct it!
Table 1 – If mean FM 6.8 kg, and mean FFM is 34.8 kg, what is the other component of body mass (73.0 kg)?
Table 2 – “In bold are p-values = ≤0.05 and trends between 0.05-0.07. LP = left pectoral; RP = right pectoral; RA= right abdomen; LA= left abdomen; RB = right back; LB = left back; RQ = right quadriceps; LQ = left quadriceps; RH = right hamstring; LH = left hamstring; RT = right tibial; LT = left tibial; RC = right calf; RC = left calf.” – These abbreviations are not used in Table 2, please correct the abbreviation!
Table 2 – it should be indicated what t-score and z-score exactly represent, i.e. t-score and z-score of total BMD?
