Title: Osteoporosis and sarcopenia are common and insufficiently diagnosed among chronic
pancreatitis patients
Version: 3 Date: 09 Feb 2023
Reviewer's report:
In this work, Parhiala and co-workers comprehensively investigated the prevalence of fat-
soluble vitamin deficiency, osteoporosis and sarcopenia in a cohort of patients with chronic
pancreatitis in Finland. They present that all three conditions are common in chronic pancreatitis
and especially osteoporosis is underdiagnosed. They further identify pancreatic exocrine
insufficiency (PEI) as a common risk factor and conclude that adequate treatment should be a
carefully monitored in patients with PEI.
The authors address a topic of high clinical relevance as data on the prevalence of these
conditions in patients with chronic pancreatitis is highly divergent and the respective risk factors
have not been fully elucidated.
Although the research question is relevant, there are several major issues, especially with regard
to methodology, that the authors have to address before this manuscript can be considered for
publication:
1) In the introduction, the background of the study is described rather vaguely so that the
relevance of the topic does not become evident. It would be helpful if the authors addressed
vitamin deficiency and osteoporosis to the same extent as sarcopenia and also the possible
interrelation between these conditions. Further, the research question addressed should be
specified in greater detail and in agreement with the title and the results presented in the
manuscript.
2) The authors need to clarify the study design. Apparently, data was collected at different time
points. In the current form, it is not possible for the reader to determine what data was collected
retrospectively and what data was obtained prospectively. I think that a graphical visualization
would be useful for that purpose. In addition, the authors should later discuss this heterogeneous
approach as a relevant limitation to their work.
3) The methods used for the measurements of bone density and muscle mass need to be presented
in more detail. Were any other methods than DXA employed for bone density measurement?
What devices or software were used? Were the conditions of measurement standardized?
Without this additional information it would be impossible to repeat the study.
4) The definition of sarcopenia applied by the author is questionable. As the authors state in their
introduction, sarcopenia is characterized by the loss muscle mass and function. This aspect is
stressed in the current international guidelines for the diagnosis of sarcopenia (PMID: 32033882;
PMID: 30312372). Yet, in their work only muscle mass is considered. Hence, it would be
indicated to use the term “possible sarcopenia” or “myopenia” throughout the entire manuscript.
Regarding the measurement of muscle mass, use of only psoas muscle is considered a non-
reliable indicator of sarcopenia by many, as it is a minor muscle and not representative of overall
sarcopenia (PMID: 28675689; PMID: 28513088). Moreover, it would be more appropriate to
standardize muscle area for height or BMI. Last, muscle area was only measured in about two-
thirds of patients which is potential source of bias and should be discussed.
5) The statistical analyses are not described in sufficient detail. In particular, the authors do
not state to what extent they accounted for normal distribution of data. Presentation as median
(range) generally indicates that variables were non-normally distributed and Mann–Whitney U
test is also generally used for non-normally distributed data. However, the authors also calculate
Pearson correlation coefficients for which normal distribution of both variable is required.
6) The discussion is written not very balanced. It is highly focused on the implications of the
findings regarding osteoporosis whereas the discussion of the results on sarcopenia is rather brief
and not all recent literature in this field is considered by the authors. Furthermore, the authors
stress the strengths of their work while potentially relevant limitations are not extensively
discussed. Especially, the methodological issues, as pointed out above, should be considered.
Minor Issues:
1) The manuscript would benefit from major language editing. The current version has many
typographical and grammatical errors, which make it difficult to correctly comprehend the text.
2) A list of abbreviations and line numbering is missing.
3) The tables and figures in this paper are not self-containing. Abbreviations should be avoided
or explained. Statistical significance, if it was tested, should also be indicated in the figures.
4) Figure 2 is rather redundant. The prevalences of osteoporosis and osteopenia are already
shown in Table 1. I suggest to include the data on sarcopenia prevalence in this table as well.
5) The criteria applied for the definitions of “clinically relevant” PEI and inadequate PERT are
rather subjective. The implication of these definitions on the results should at least be discussed.
6) The authors report odds ratios. However, calculation of odds ratios is not described in the
statistical analyses. Odds ratios should be reported with 95% confidence intervals.
7) Different units for psoas muscle area are used throughout the manuscript (i.e. mm2 and cm2).
8) The final sentence of the conclusions part is rather generic. The authors should specify what
interventions could be tested in the future.
Title: Osteoporosis and sarcopenia are common and insufficiently diagnosed among chronic
pancreatitis patients
Version: 3 Date: 09 Feb 2023
Reviewer's report:
In this work, Parhiala and co-workers comprehensively investigated the prevalence of fat-
soluble vitamin deficiency, osteoporosis and sarcopenia in a cohort of patients with chronic
pancreatitis in Finland. They present that all three conditions are common in chronic pancreatitis
and especially osteoporosis is underdiagnosed. They further identify pancreatic exocrine
insufficiency (PEI) as a common risk factor and conclude that adequate treatment should be a
carefully monitored in patients with PEI.
The authors address a topic of high clinical relevance as data on the prevalence of these
conditions in patients with chronic pancreatitis is highly divergent and the respective risk factors
have not been fully elucidated.
Although the research question is relevant, there are several major issues, especially with regard
to methodology, that the authors have to address before this manuscript can be considered for
publication:
1) In the introduction, the background of the study is described rather vaguely so that the
relevance of the topic does not become evident. It would be helpful if the authors addressed
vitamin deficiency and osteoporosis to the same extent as sarcopenia and also the possible
interrelation between these conditions. Further, the research question addressed should be
specified in greater detail and in agreement with the title and the results presented in the
manuscript.
2) The authors need to clarify the study design. Apparently, data was collected at different time
points. In the current form, it is not possible for the reader to determine what data was collected
retrospectively and what data was obtained prospectively. I think that a graphical visualization
would be useful for that purpose. In addition, the authors should later discuss this heterogeneous
approach as a relevant limitation to their work.
3) The methods used for the measurements of bone density and muscle mass need to be presented
in more detail. Were any other methods than DXA employed for bone density measurement?
What devices or software were used? Were the conditions of measurement standardized?
Without this additional information it would be impossible to repeat the study.
4) The definition of sarcopenia applied by the author is questionable. As the authors state in their
introduction, sarcopenia is characterized by the loss muscle mass and function. This aspect is
stressed in the current international guidelines for the diagnosis of sarcopenia (PMID: 32033882;
PMID: 30312372). Yet, in their work only muscle mass is considered. Hence, it would be
indicated to use the term “possible sarcopenia” or “myopenia” throughout the entire manuscript.
Regarding the measurement of muscle mass, use of only psoas muscle is considered a non-
reliable indicator of sarcopenia by many, as it is a minor muscle and not representative of overall
sarcopenia (PMID: 28675689; PMID: 28513088). Moreover, it would be more appropriate to
standardize muscle area for height or BMI. Last, muscle area was only measured in about two-
thirds of patients which is potential source of bias and should be discussed.
5) The statistical analyses are not described in sufficient detail. In particular, the authors do
not state to what extent they accounted for normal distribution of data. Presentation as median
(range) generally indicates that variables were non-normally distributed and Mann–Whitney U
test is also generally used for non-normally distributed data. However, the authors also calculate
Pearson correlation coefficients for which normal distribution of both variable is required.
6) The discussion is written not very balanced. It is highly focused on the implications of the
findings regarding osteoporosis whereas the discussion of the results on sarcopenia is rather brief
and not all recent literature in this field is considered by the authors. Furthermore, the authors
stress the strengths of their work while potentially relevant limitations are not extensively
discussed. Especially, the methodological issues, as pointed out above, should be considered.
Minor Issues:
1) The manuscript would benefit from major language editing. The current version has many
typographical and grammatical errors, which make it difficult to correctly comprehend the text.
2) A list of abbreviations and line numbering is missing.
3) The tables and figures in this paper are not self-containing. Abbreviations should be avoided
or explained. Statistical significance, if it was tested, should also be indicated in the figures.
4) Figure 2 is rather redundant. The prevalences of osteoporosis and osteopenia are already
shown in Table 1. I suggest to include the data on sarcopenia prevalence in this table as well.
5) The criteria applied for the definitions of “clinically relevant” PEI and inadequate PERT are
rather subjective. The implication of these definitions on the results should at least be discussed.
6) The authors report odds ratios. However, calculation of odds ratios is not described in the
statistical analyses. Odds ratios should be reported with 95% confidence intervals.
7) Different units for psoas muscle area are used throughout the manuscript (i.e. mm2 and cm2).
8) The final sentence of the conclusions part is rather generic. The authors should specify what
interventions could be tested in the future.
Please review this paper.
user
Title: Osteoporosis and sarcopenia are common and insufficiently diagnosed among chronic
pancreatitis patients
Version: 3 Date: 09 Feb 2023
Reviewer's report:
In this work, Parhiala and co-workers comprehensively investigated the prevalence of fat-
soluble vitamin deficiency, osteoporosis and sarcopenia in a cohort of patients with chronic
pancreatitis in Finland. They present that all three conditions are common in chronic pancreatitis
and especially osteoporosis is underdiagnosed. They further identify pancreatic exocrine
insufficiency (PEI) as a common risk factor and conclude that adequate treatment should be a
carefully monitored in patients with PEI.
The authors address a topic of high clinical relevance as data on the prevalence of these
conditions in patients with chronic pancreatitis is highly divergent and the respective risk factors
have not been fully elucidated.
Although the research question is relevant, there are several major issues, especially with regard
to methodology, that the authors have to address before this manuscript can be considered for
publication:
1) In the introduction, the background of the study is described rather vaguely so that the
relevance of the topic does not become evident. It would be helpful if the authors addressed
vitamin deficiency and osteoporosis to the same extent as sarcopenia and also the possible
interrelation between these conditions. Further, the research question addressed should be
specified in greater detail and in agreement with the title and the results presented in the
manuscript.
2) The authors need to clarify the study design. Apparently, data was collected at different time
points. In the current form, it is not possible for the reader to determine what data was collected
retrospectively and what data was obtained prospectively. I think that a graphical visualization
would be useful for that purpose. In addition, the authors should later discuss this heterogeneous
approach as a relevant limitation to their work.
3) The methods used for the measurements of bone density and muscle mass need to be presented
in more detail. Were any other methods than DXA employed for bone density measurement?
What devices or software were used? Were the conditions of measurement standardized?
Without this additional information it would be impossible to repeat the study.
4) The definition of sarcopenia applied by the author is questionable. As the authors state in their
introduction, sarcopenia is characterized by the loss muscle mass and function. This aspect is
stressed in the current international guidelines for the diagnosis of sarcopenia (PMID: 32033882;
PMID: 30312372). Yet, in their work only muscle mass is considered. Hence, it would be
indicated to use the term “possible sarcopenia” or “myopenia” throughout the entire manuscript.
Regarding the measurement of muscle mass, use of only psoas muscle is considered a non-
reliable indicator of sarcopenia by many, as it is a minor muscle and not representative of overall
sarcopenia (PMID: 28675689; PMID: 28513088). Moreover, it would be more appropriate to
standardize muscle area for height or BMI. Last, muscle area was only measured in about two-
thirds of patients which is potential source of bias and should be discussed.
5) The statistical analyses are not described in sufficient detail. In particular, the authors do
not state to what extent they accounted for normal distribution of data. Presentation as median
(range) generally indicates that variables were non-normally distributed and Mann–Whitney U
test is also generally used for non-normally distributed data. However, the authors also calculate
Pearson correlation coefficients for which normal distribution of both variable is required.
6) The discussion is written not very balanced. It is highly focused on the implications of the
findings regarding osteoporosis whereas the discussion of the results on sarcopenia is rather brief
and not all recent literature in this field is considered by the authors. Furthermore, the authors
stress the strengths of their work while potentially relevant limitations are not extensively
discussed. Especially, the methodological issues, as pointed out above, should be considered.
Minor Issues:
1) The manuscript would benefit from major language editing. The current version has many
typographical and grammatical errors, which make it difficult to correctly comprehend the text.
2) A list of abbreviations and line numbering is missing.
3) The tables and figures in this paper are not self-containing. Abbreviations should be avoided
or explained. Statistical significance, if it was tested, should also be indicated in the figures.
4) Figure 2 is rather redundant. The prevalences of osteoporosis and osteopenia are already
shown in Table 1. I suggest to include the data on sarcopenia prevalence in this table as well.
5) The criteria applied for the definitions of “clinically relevant” PEI and inadequate PERT are
rather subjective. The implication of these definitions on the results should at least be discussed.
6) The authors report odds ratios. However, calculation of odds ratios is not described in the
statistical analyses. Odds ratios should be reported with 95% confidence intervals.
7) Different units for psoas muscle area are used throughout the manuscript (i.e. mm2 and cm2).
8) The final sentence of the conclusions part is rather generic. The authors should specify what
interventions could be tested in the future.
assistant