Reviewer ’s report  
 
Title: Clinical effects of switching from minodronate to denos umab treatment in patients with 
postmenopausal oste oporosis: A retrospective study  
 
Version: 0 Date: 25 Nov 2019  
 
Reviewer: Luiz F. Baccaro  
 
Reviewer's report:  
 
The article "Clinical effects of switching from minodronate to denosumab treatment in patients 
with postmenopausal osteoporosis: a retrospective study" assesses the effects of switching from 
minodronate therapy to denosumab on bone mass and bone turnover m arkers. The topic is of 
interest to the readers of the newspaper because it deals with a very prevalent disease 
(osteoporosis). The article is well structured and well written; however, some aspects need major 
revision before it can be considered for publi cation.  
 
 
Background  
 
Page 5 Line 32 -  "Large clinical trials reported denosumab´s sales exceeds that of each 
bisphosphonate". References cited are not clinical trials and are in Japanese. Probably reports on 
drug sales in Japan.  
 
Methods  
The authors re port that this was a retrospective study conducted from January 2012 to December 
2018. The authors report that they offered the switch from minodronate to denosumab and that 
they evaluated bone mineral density semiannually and bone turnover markers annuall y for two 
years. This study design is not retrospective. The authors performed a prospective study with one 
intervention (drug change counseling). The study would be better classified as an open -label, 
non-randomized clinical trial.  
If the authors consid er the study to be retrospective, it should be clear to the reader that the 
suggested change in medication was due to the fact that physicians believed that this would be a 
better conduct rather than because it was a study. However, it would not make sense  to perform 
bone densitometry every 6 months if not for a prospective study. Please clarify.  
Did all women included have exactly two years of minodronate use? Or was this the minimum 
time to be included in the study? If this is the minimum medication use  time, describe the mean 
time of use of minodronate in each group.  
What is the reason for considering L2 -L4 and not L1 -L4 bone mass?  
The authors make no mention of calculating sample size or sample power. Please clarify.  
Why was calcium and vitamin D  supplementation different between the two study groups?  
 
Results  
Table 1 : Mean time since menopause should be shown in Table 1  
Table 1 : Please provide statistical test used for p -value.   
Discussion  
 
Page 12 Line 36 : "This result indicates the clinical benefit of switching therapy in comparison 
with MIN continuous treatment."  For this statement to be made, the study would have to have 
shown a reduction in the incidence of fractures.  
 
Comment on the  problem of prolonged bisphosphonate use, and switching to denosumab would 
be an alternative.  
Page 14 Line 3 : "Considering the relatively lower persistence of oral bisphosphonates, switching 
to another treatment option might be valid if patients do not acquire estimated effects on bone 
metabolism after a certain period of oral bisphosphonate treatment".  The group that continued 
the use of minodronate did not gain bone mass, but also did not lose bone mass. This is not 
necessarily a bad outcome in treat ing osteoporosis. The fact that they maintained bone mass can 
be considered a positive fact.  
Page 15 Line 3 : "but the serum calcium concentration of the subject was within normal range."  
These calcium values should be reported in the results section.  
Page 15 Line10 : "Possible severe adverse events that might occur after long -term 
bisphosphonate use are atypical femoral fracture and osteonecrosis of the jaw; however, no 
subjects in this study presented those complications."  minodronate use time (2 years) was short 
to consider adverse events such as atypical femoral fracture and osteonecrosis of the jaw  
The use of denosumab reduced alkaline phosphatase concentrations, which did not occur with 
minodronate. Alkaline phosphatase is a marker of bone fo rmation. The authors did not 
sufficiently discuss these findings. A longer discussion about bone turnover markers should be 
made.  
The paragraph on limitations should state that the authors did not analyze fractures  
Page 15 Line 51 : "This switching the rapy is valid and can be one of the effective treatment 
options for postmenopausal osteoporosis". Based on the results of this study the authors cannot 
have such an affirmative conclusion.  
 
 
 
Are the methods appropriate and well described?  
If not, please specify what is required in your comments to the authors.  
 
No 
 
Does the work include the necessary controls?  
If not, please specify which controls are required in your comments to the authors.  
 
Yes 
 
Are the conclusions drawn adequately supported by the data shown?  
If not, please explain in your comments to the author s. 
 
No 
Are you able to assess any statistics in the manus cript or would you recommend an 
additional statistical review?  
If an additional statistical review is recommended, please speci fy what aspects require further 
assessment in your comments to the editors.  
 
I recommend additional statistical review  
 
Quality of written English  
Please indicate the quality of language in the manuscript:  
 
Acceptable  
 
Declaration of competing interests  
Please complete a declaration of competing in terests, considering the following questions:  
 
1. Have you in the past five years received reimbursements, f ees, funding, or salary from an 
organisation that may in any way gain or lose financial ly from the publication of this 
manuscript, either now or in t he future?  
 
2. Do you hold any stocks or shares in an organisation t hat may in any way gain or lose 
financially from the publication of this manuscript, either now or in the future?  
 
3. Do you hold or are you currently applying for any patents relating to th e content of the 
manuscript?  
 
4. Have you received reimbursements, fees, funding, or salary from an organization that 
holds or has applied for patents relating to the content of the manuscript?  
 
5. Do you have any other financial competing interests?  
 
6. Do y ou have any non -financial competing interests in relation to this paper?  
 
If you can answer no to all of the above, write 'I declare that I have  no competing interests' 
below. If your reply is yes to any, please give details below.  
 
I declare that I have no competing interests  
 
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