Copper as Dietary Supplement for Bone Metabolism: A Review

Round 1

Reviewer 1 Report

The authors have adequately addressed most, but not all, of the comments raised and in my opinion have significantly improved the manuscript. I think that the manuscript now merits publication in Nutrients.

Reviewer 2 Report

The resubmitted version is much improved according to the reviewers suggestions.

Reviewer 3 Report

The authors insist on keeping the format as a narrative review, and have not addressed the points raised in my previous review.

I am very concerned about the scientific quality of a narrative review, as there is a very high risk of selective reporting. Thus, the review does not contribute to pointing towards future research.

 

 

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

Thank you for the opportunity to evaluate this work.

I recommend that PRISMA checklist is applied rigorously in the reporting of the present review.

I have applied AMSTAR 2 as checklist for evaluating the internal validity in terms of the methodological quality and reporting of the review. I am very concerned about the scientific quality and contribution of this work. There is a high risk of selective reporting, and the review does not contribute to pointing towards future research.  

1. The research questions and inclusion criteria for the review did not include the components of PICO (population, intervention, comparator, outcomes). Please revise accordingly.
2. The report of the review did not contain an explicit statement that the review methods were established prior to the conduct of the review and did the report justify any significant deviations from the protocol. Thus, there is a high risk of selective reporting.
3. The review authors did not explain their selection of the study designs for inclusion in the review. Please revise accordingly.
4. The review authors did not report on the literature search strategy. Please revise accordingly. PRISMA-S can be used as reporting framework:

PRISMA-S: an extension to the PRISMA Statement for Reporting Literature Searches in Systematic Reviews

5. The review authors did not report on how the study selection was performed. Please revise accordingly.
6. The review authors did not report on how the data extraction was performed. Please revise accordingly.
7. The review authors did not provide a list of excluded studies. Please revise accordingly.
8. The review authors should describe the included studies in adequate detail according to PICO, research design, study setting and time-frame for follow-up. Please revise accordingly.
9. The review authors did not assess the risk of bias (RoB) in individual studies that were included in the review. Please use Cochrane Risk of Bias tool for RCTs, and ROBINS-I for non-RCTs.
10. The review authors should report on the sources of funding for the studies included in the review.
11. Please provide a rationale for why meta-analyses were not conducted. If a meta-analysis is not conducted, please use SWIM as reporting framework:

Synthesis without meta-analysis (SWiM) in systematic reviews: reporting guideline

BMJ 2020; 368 doi: https://doi.org/10.1136/bmj.l6890 (Published 16 January 2020)

12. The review authors should account for RoB in individual studies when interpreting/ discussing the results of the review.
13. The review authors should provide a satisfactory explanation for, and discussion of, any heterogeneity observed in the results of the review.
14. The review authors should discuss the risk of publication bias, and the impact of the results of the review.

 

Reviewer 2 Report

There are two groups of minerals which have important roles in bone metabolism : macro -minerals and micro-minerals  or trace elements : boron, copper, iron, selenium and zinc. Trace elements may impact bone metabolism indirectly or directly affecting bone cells proliferation or their activity,  therefore the review deals with a topic of potential interest for the readers. In the review however,  the authors should  comment  on the other recent review on this topic published in 2018 in Biol Trace Elements.

There is one important issue missing in the submitted review - the authors did not mention which were the methods for measuring the level of copper in the articles they analyzed , which is important from the practical point of view : whether a serum copper concentrations were measured, a serum ceruloplasmin concentrations or 24-h urine copper levels were assayed. 

It seems that the authors are not familiar with the methods for assessment of bone turnover by measurement of bone turnover markers namely, bone formation markers and bone resorption markers. Reabsorption has nothing to do with bone resorption. Calcium can be reabsorbed but the bone undergoes resorption.

Also some typo should be corrected  : page 2, line 62, should be – hydroxylysine ; page 2 line 66 – should be Li et al.

 

Reviewer 3 Report

In this interesting review, Rondanelli and colleagues discuss copper as dietary supplement for bone metabolism. Their aim was to investigate the correlation between blood copper, daily copper intake and copper supplementation and bone mineral density. Therefore they analyzed 10 eligible studies. Only one study showed differences between osteoporotic and healthy women. The dietary copper intake among women with or without osteoporosis didn’t show differences in this study. Two studies that analyzed the integration of copper showed promising results in terms of slowing down bone mineral loss and reducing reabsorption markers. The authors conclude from these two studies that they confirm the effectiveness of copper supplementation on bone metabolism.

 

This is a very well written review, which gives us a bright overview over the relationship about copper as dietary supplement for bone metabolism. I have only minor remarks, which I believe are important for the completion of this review.

In all Studies which are listed that considered blood copper levels only women were analysed. Are there any other studies which show the copper level in men? Since 20% of men are also affected by osteoporosis?

1. In general the content of single columns should be coherent.

 

2. The tables are filled with lot of information, not all oft them are necessary. The authors should reduce the content of single columns to a minimum which is necessary. For example inclusion and exlusion critera.

 

3. Setting could be replaced by Instutition and country. Which should have the information of the Instutition, City and country.