Title: Association between parity and bone mineral density in postmenopausal women
Version: 1 Date: 15 Jan 2022
Reviewer:  Gregor Prša
Reviewer's report:
In my opinion the article is well written with a large sample size. Your results confirm the
conclusions from earlier studies, that high parity is a risk factor for low bone mineral density
(BMD) in postmenopausal women.
The focus of the article is very well put together with a good background description and
discussion development. However, there are some important methodological issues that need
to be taken into account.
There are some minor grammatical mistakes. For example: “Methods” should be written with the
capital letter. In discussion, write to provide “calcium for milk production” instead of “to provide
calcium to milk”. In the discussion section you have written: “the number of eligible nulliparous
women was too small to be excluded from the analysis”. You probably meant “included”.
In abstract, the Methods section is insufficient and only describes statistical analysis.
Figures and tables: the colons are missing. The DXA scans of the proximal femur and lumbar
spine were “performed” instead of “administered” at the NHANES mobile examination center.
In table 1, the numbers are rounded up to three decimals, which is too much. Why did you
perform a weighted analysis on these data and what did you weight them for? You should add
the mark for standard deviation in the first column next to the name of the variable. Moreover,
consider adding the range for numerical variables.
In the statistical analysis segment, you defined how a statistical analysis was performed on
Model 1, 2, and 3. However you did not describe the statistical analysis of basic demographic
characteristics (table 1).
Considering a question from the questionnaire, only women that gave birth to live babies were
included. In my opinion stillbirths should also be included as pregnancy alone can affect the
bone mineral density.
Physical activity should be quantified because its quantity plays a significant role in BMD later
in life.
Other important risk factors for the development of osteoporosis should be taken into
consideration, for example: corticosteroid, heparin and anticonvulsive drug use in the past,
history of transplantation, liver disease, rheumatologic disease as rheumatoid arthritis, and
other common diseases like celiac disease, chronic inflammatory bowel disease and chronic
pulmonary obstructive disease.
For the alcohol usage 12 drinks per year is probably is not a relevant discrimination factor to
properly assess the risk of osteoporosis development. Why did you choose this cut-off points?
You stated that absorption of calcium doubles during pregnancy to meet the needs of a
developing foetus. Furthermore, the skeletal resorption increases during lactation to provide
calcium for milk production. In this view, adding breastfeeding duration could be an important
factor in the assessment of risk for osteoporosis development.
Furthermore, considering hormonal replacement therapy as a confounding variable would be
reasonable. How many patients with early menopause were included in the study? And if any, the
duration of hormonal replacement therapy for these patients should be determined and evaluated.
You did not define, which cancer patients were excluded from the study-only patients with
present cancer disease or also the patients with a history of cancer?
In the future a larger sample of nulliparous women would be beneficial, so that you could assess
the impact of pregnancy alone on MBD later in life.
I would also consider adding a discussion about the difference in MBD in lumbar spine and
femoral bone. Why was this difference also observed by other researchers and how do you
explain these findings?
In the discussion you are talking about a representative sample for American population. It is
questionable whether this is true because you excluded patients with cancer, nulliparous women,
and women in their reproductive period. Please rephrase this statement.
Furthermore, you stated that you performed a multiethnic population analysis, which can not be
seen from your results, as you only divided women according to their parity.
You did not take in consideration the number of patients already diagnosed with osteoporosis
and how many of them already received treatment for the disease.
Moreover, you determined that there are differences in BMD between groups, but how does this
translate into number of women in each group that would be diagnosed with osteoporosis or
osteopenia? Is the number of these women also statistically different between groups? Adding
this information to your manuscript would make you findings clinically significant.