Diagnosis, Follow-Up and Therapy for Secondary Osteoporosis in Vulnerable Children: A Narrative Review

Round 1

Reviewer 1 Report

The review by Dittrich et al. describes in a narrative manner the diagnosis and therapy for secondary osteoporosis in vulnerable children. The review is well-written, easy to read, and presents information in a sensible manner. Below are some specific comments to further improve the manuscript.

 

Specific comments:

Abstract:

Consider introducing the abbreviation DXA.

 

Introduction

• It should be specified that primary osteoporosis in children such as from OF is distinctly different from primary osteoporosis in adults which manifests as a result of ageing.
• P2, L60: Reference needed. Please be sure to have included all relevant references and removed comments from the manuscript writing process.
• Consider providing a bit more background information as to why the three groups of children (disabled, keto, and myopathies) are chosen in particular compared to the hundreds of different other factors/co-morbidities that could have been addressed as well.
• Omit decimals on numbers (e.g. 10.1%, 32.5% etc.).

 

Diagnosis

• Ref? Please provide the correct reference wherever needed.
• pQCT is also a possibility for the diagnosis of osteoporosis. Please elaborate on the use of pQCT in children.

 

Potential for recovery

• For both immobilization and GC-induced osteoporosis, consider including a short paragraph about the emerging role of animals to model such types of bone loss in children (immobilization: Brent et al. Calcif Tissue Int. 2021 May;108(5):561-575. doi: 10.1007/s00223-020-00799-9 and Tang et al. Toxins (Basel). 2021 Mar; 13(3): 213. 2021 Mar 14. doi: 10.3390/toxins13030213) and (GC: J Endocrinol . 2018 Jan;236(1):R69-R91. doi: 10.1530/JOE-17-0361).

 

Figures:

Figure 1: “After 12 months” seems a bit out of place on the figure. Consider a re-organization.

Author Response

We would like to thank the reviewer for the valuable comments. Here we answer them, point by point.

Abstract:

Consider introducing the abbreviation DXA.

We introduced this abbreviation, line 30.

Introduction

• It should be specified that primary osteoporosis in children such as from OF is distinctly different from primary osteoporosis in adults which manifests as a result of ageing.

We are no experts in adult medicine, so we have clarified more that this article is about secundary osteoporosis in children (lines 47-50)  

• P2, L60: Reference needed. Please be sure to have included all relevant references and removed comments from the manuscript writing process.

In line 60 the reference is added. Also we checked the whole manuscript for 'comments from the writing process'. 

• Consider providing a bit more background information as to why the three groups of children (disabled, keto, and myopathies) are chosen in particular compared to the hundreds of different other factors/co-morbidities that could have been addressed as well.

We have given a little bit more attention to the reason why we have chosen these three groups of children (see lines 78-79)

• Omit decimals on numbers (e.g. 10.1%, 32.5% etc.).

We think it is not right to omit decimals on numbers we cite from other research. 

Diagnosis

• Ref? Please provide the correct reference wherever needed.

We added several references in the diagnosis section.

• pQCT is also a possibility for the diagnosis of osteoporosis. Please elaborate on the use of pQCT in children.

We have included the following section on pQCT:

(HR-) pQCT is used to measure cortical and trabecular volumetric bone mineral density separately and bone micro architectural morphology. Movement artifacts are a real limitation (A). The use of (HR-) pQCT is limited due to the lack of standardized pediatric reference data for young children and the fact that only few (HR-) pQTC scanners are available for patient care. The correlation coefficient of (HR-) pQCT with DXA is only 0.57 (21). Quantitative ultrasound has the same correlation coefficient. (lines 156-164 and some remarks earlier in this section)

Potential for recovery

• For both immobilization and GC-induced osteoporosis, consider including a short paragraph about the emerging role of animals to model such types of bone loss in children (immobilization: Brent et al. Calcif Tissue Int. 2021 May;108(5):561-575. doi: 10.1007/s00223-020-00799-9 and Tang et al. Toxins (Basel). 2021 Mar; 13(3): 213. 2021 Mar 14. doi: 10.3390/toxins13030213) and (GC: J Endocrinol . 2018 Jan;236(1):R69-R91. doi: 10.1530/JOE-17-0361).

We have added a short paragraph for immobilization (lines 199-202) and for glucocortocoids (lines 239-241)

Figures:

Figure 1: “After 12 months” seems a bit out of place on the figure. Consider a re-organization.

We re-organized the figure. 

Reviewer 2 Report

The review is interesting to me.  However, In the text the authors missed several references that authors intent to add. Please read the text carefully and revise accordingly.

Such as

1.  "during adolescence (reference needed)."

2. "were asymptomatic (REF, check)."

3. "deformity (ref).

4. "less (ref). With

5."of vertebral bodies (reference).

6."methotrexate (REF)."

Author Response

We would like to thank the revieuwer for the valuable comments. 

We have added the references, as the reviewer asked.

1.  "during adolescence (reference needed)." Reference 5

2. "were asymptomatic (REF, check)." Reference 8

3. "deformity (ref). Reference 8

4. "less (ref). Reference 4

5."of vertebral bodies (reference). reference 59

6."methotrexate (REF)." Reference 32

 

Reviewer 3 Report

The authors carry out an extensive non-systematic review of a relevant and difficult-to-manage health problem, osteoporosis in children and its therapeutic management. The final part of the article refers to three situations where osteoporosis may be more prevalent.

In general, the structure of the article makes it difficult to read due to the absence of subsections, associated tables and few images. The division of the different sections into subsections as well as some images could facilitate their reading

The first section referring to the diagnosis does not make clear the procedure to follow. It is possible that an algorithm could make it easier to understand.

It might be interesting to add a differential diagnosis section that includes diseases associated with fractures (osteogenesis imperfecta, hypophosphatasia) In the therapeutic section, indicate why there are no data with other therapeutic options or their use is not indicated

Author Response

We would like to thank the reviewer for the valuable comments. 

Here the answers, point by point. 

- In general, the structure of the article makes it difficult to read due to the absence of subsections, associated tables and few images. The division of the different sections into subsections as well as some images could facilitate their reading

We replaced the subsection 'Potential for recovery' in the manuscript to a more logical place, and inserted extra subsections (lines 344-378). 

- The first section referring to the diagnosis does not make clear the procedure to follow. It is possible that an algorithm could make it easier to understand.

We provide practical information about who and how to screen in the section 'Screening for secondary osteoporosis'. We now refer to this information in the 'diagnosis' section.

- It might be interesting to add a differential diagnosis section that includes diseases associated with fractures (osteogenesis imperfecta, hypophosphatasia)

Yes, this might be interesting, but we choose not to do this, because this is not the scope of this manuscript.

 - In the therapeutic section, indicate why there are no data with other therapeutic options or their use is not indicated

There are no other evidence based therapeutic options indicated in children in this moment. This narrative review is not ment to speculate on possible future protocolair therapeutic options like denosumab. 

Round 2

Reviewer 3 Report

The paper can be accept