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oe برای چاپ و
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بن جانقربانى
٠ اپیدمیولوژی
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مراحل آماده ۱ نام
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وت
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5 ارسالی
۸۵ 5316۳06۳01 0۴ 0۸۵۳۱61۵1 ٩ ۲
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ae 0 و رد سور
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و
تصمیم ها و پاسخها
گ و مشروط
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ار س0 رح مقدماتى رئوس مطالب ٠ ساختار
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Mayer B. Davidson, M.D.
Editor-in-Chief, Diabetes Care
6919 E. Tenth Street, Suite B-2
Indianapolis, IN 46219
27 March 2006
Dear Prof. Davidson;
Thank you very much for your email and referees’ comments dated 16
March 2006 regarding our manuscript (DCO6-0440R “PROSPECTIVE STUDY
OF DIABETES MELLITUS AND RISK OF HIP FRACTURE: THE NURSES’ HEALTH
STUDY"). We attach a revised manuscript taking into account the reviewers’
comments as follows:
Reviewer A Comments:
This is a well done study with appropriate analyses and conclusions.
Having so large a study group enables you to have an adequate sample of
diabetic patients to do a strong analysis. You make a valid point that fracture
prevention is an important part of the care of women with diabetes.
Reply: Thank you very much.
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Reviewer B Comments:
This is a well-written fine article about the association between type 1 and 2 diabetes
mellitus and risk of hip fracture. The authors present a conclusion that both type 1 and
type 2 diabetes increase the risk of hip fracture in women. Although the authors
emphasize the advantages of their huge sample size, there is however a danger of
false positive finding in such a large cohort. Although the cohort was originally not
planned to study hip fractures, and the authors were not there to perform any power
calculations in the beginning, did the authors calculate how many women they would
need to show the clinically and statistically significant difference in the rate of fractures
and risk ratios? | suggest the authors remove the conclusion concerning the duration of
type 2 diabetes from the conclusion section, page 13 (In summary, our...) as they have
done in the abstract section. This conclusion can not be drawn due to the probably high
frequency of undiagnosed type 2 diabetics. The finding is interesting but may not be
included in the final conclusions.
Reply: We acted on suggestion made by reviewer B and removed the conclusion
regarding duration of type 2 diabetes from the conclusion section of Discussion. About
sample size, this study is one of the largest cohort studies to date of a relationship
between diabetes and risk of hip fracture. Regarding power analysis, on the basis oF
previous estimates of hip fracture incidence of 1%, we calculated that 1,225 wemen
with type 2 diabetes and 12,250 women without diabetes would be required to pfoyide:
the stildy with 80 percent power to detect (with a two-sided alpha of 0.05) a felative
risk of hip fracture in type 2 diabetes 2.0. Regarding power analysis in type 1 digbetes,
on the basis of post hoc estimates of relative risk of 6.0 for type 1 diabetes, we
calculated that 84 women with type 1 diabetes and 5,796 women without diabetes
would be required to provide the study with 80 percent power to detecti(with a two-
sided alpha of 0.05) a relative risk of hip fracture in type 1 diabetes 6.0, We did not
Gar iicia these aware calianae Boealien Paeebatictical uncertainty حم و اس کی
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Reply: We have added the following in the Results section to describe the
mean age of women at the time of hip fracture: The mean (SD) age of hip
fracture was 65.6 (8.3) years for nondiabetics, 65.3 (7.4) years for type 1,
and 68.6 (7.2) years for type 2 diabetes.
Comment- Abstract: Typo error in "Research design and methods" (desighn)
Typo error in "Results": ..the age adjusted relative risk...(risks).
Reply: The English editing has been done.
Comment- Introduction: Please be more careful when referring to previous
studies. There are several mistakes in the references. For example, it is said
in the Introduction section, first paragraph, line 12, that: ...whereas others
reported no association (...23), but in the Discussion section, page 9, line 8,
the same reference (23) is quoted ...type 1 diabetes was associated with
increased risk of proximal humerus fractures. In the Introduction, line 13,
reference 25 is quoted as ..."whereas others reported no association or even
an inverse relation (..25). In fact, the results in SOF revealed that the women
with diabetes were at increased risk of intra-articular radial fractures, not
decreased. Furthermore, in the Introduction, line 9, the reference 21 is not in
the right place. Ref 21 is a study which showed an inverse association
between type 2 diabetes and bone mass and fractures, not type 1 diabetes
and fractures. | suggest the authors remove the Ref 21 from the line 9, and
change the places of Ref 25 and 21 in the lines 12 and 13. Furthermore, |
suggest the authors concentrate on their literature review more on studies
that have evaluated the association between diabetes and hip fractures, not
on wrist or other minor fractures. The authors state that the samples in the
previous studies have been small, but for example the Swedish cohort
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Reply: We acted on suggestion made by reviewer B and corrected the
references accordingly and removed sentences indicate previous studies
have been small.
Comment- Important risk factors for hip fracture include risk factors of
falling, for example balance disturbances, muscle function, functional ability,
walking ability, walking speed etc. Did the questionnaires include any
questions about self rated mobility, balance, muscle strength, difficulties in
daily activities, difficulties in ADL or IADL due to impaired vision, fear of
falling, fall history etc. If not, | suggest these will be include in future
questionnaires.
Reply: Unfortunately, in our database information about self rated mobility,
balance, muscle strength, difficulties in daily activities, difficulties in ADL or
JADL due to impaired vision, fear of falling, fall history etc. was not recorded
at baseline. Some of this has been collected in more recent questionnaires
and, with additional follow-up, will serve as the basis for future analyses.
Comment- Analysis: At what stage and why did the authors classify the
duration of type 2 diabetes into three classes? Why did you not handle the
duration as a continuous تس
Reply: The classification of duration of diabetes was done 2
examination of the distribution of duration to have an adequate nung 4
person-time in each category. We believe a categorical analysis is useful
because it conveys information about the actual distribution of duration in
our study and also the corresponding relative risks. The analysis was als0
performed with duration of diabetes as continuous covariate amt the result
was similar. The P for trend is the analysis with duration of diabetes as a
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Comment- Results: In the Abstract, Results section you mention the years
(>=12 years), but not in the text, Results section, page 8, where you state
that "Women with longer duration of type 2 diabetes tended to...". Please be
more precise also in the text. The abstract should be a summary of the text.
In the Results, Incidence section, please refer to the Table 2.
Reply: We have made the amendment according to the suggestion and the
following sentence addressed in Results section: “Women with longer
duration of type 2 diabetes tended to have a higher risk of fracture than did
diabetics with a shorter duration (RR 3.1; 95% Cl 2.3, 4.0, for =12 years
compared to no diabetes, P for trend <0.001)". We also referred to Table 2 in
the Incidence section of Results.
Comment - Conclusions, page 11, 3rd paragraph: | think the readers would
appreciate more profound discussion about the possible explanations
concerning the association between insulin treatment and increase risk of hip
fractures. Does insulin not have an osteogenic effect as previously
suggested?
Reply: We have made the amendment according tothe
suggestion.Comment- Conclusions, last page: The sentence وه
summary, our..." is not clear. | Would suggest "In summary, ougstudy
indicates that women with type 1 or type 2 diabetes are at increased, risk for
hip fracture."Reply: We have made the changes according to the suggestion.
We thank this reviewer for his/her careful reading of our manuScript and
constructive siiggestions.
=
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These are further data based on the large prospective observational Nurses' health
study. This study had provided lots of valuable information re women's health. Most
of the participants are Caucasian but this acknowledged by the authors. The paper is
very well written and easy to understand. It sends an important message to clinicians
caring for people with diabetes. We rightly spend a lot of time and effort reducing
macrovascular/renal/visual/foot complications but don't think that much about
preventing the morbidity and mortality (and expense) due to fragility fracture. This
may be because many diabetologists don't "do bones"! However, the RR for hip
fracture shown here for type 1 diabetes is greater than most other recognized
independent risk factors used to predict risk of fragility fracture. The study also
demonstrates the increased risk in Type 2 diabetes. This is also an important clinical
point. Many health care professionals tend to think that fracture risk just relates to
bone density, which in people with type 2 diabetes is often not low enough to classify
as osteoporosis. However most fractures occur in individuals with osteopenia (not
osteoporosis) - hence the importance preventing fragility fracture by assessing and
reducing falls risk in our patients with reduced vision and neuropathy. Preventing
fragility fracture is like managing diabetes — it’s about education and interdisciplinary
collaboration. Diabetologists should be good at it. This paper will hopefully encourage
clinicians to prevent yet another unpleasant complication
Reply: We thank the reviewer for his/her advice.
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6919 E. Tenth St., Suite B-2
Indianapolis, IN 46219
February, 2006 of
;Dear Prof. Davidson
Please find enclosed a copy of a paper entitle “PROSPECTIVE STUDY OF
DIABETES MELLITUS AND RISK OF HIP FRACTURE: THE NURSES’
HEALTH STUDY” for publishing in Diabetes Care. | takes full responsibility
for the data presented in this study, analysis of the data, conclusions, and
conduct of the research. | had full access to data and has maintain the right
to publish any and all data independent of any third party. The Ethical
Review Committee of Harvard School of Public Health and Brigham and
Women’s Hospital approved the study protocol. | confirm that neither the
manuscript submitted nor any part of it has been published or is being
considered for publication elsewhere
.Would you please consider it for publication and let me know your decision
.Thank you very much in advance
;Sincerely yours
M. Janghorbani, PhD
Prof. of Epidemiology.
Dept. of Epidemiology and
Biostatistics
School of Public Health
Isfahan University of Medical
وزج
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Ole نرسیده يا جهت چاپ دردست بررسی نمی باشد و تا دریافت ياسخ
١ مرتعالى قصذ انتشار أن را در سایر ۲ ۱۱ ۱۲
قبلااز بذل توجه حضرتعالی سپاسگزارم.
با احترام دکتر محسن جانقربانی
استاد اپیدمیولوژی
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