Alendronate Prevents Early Periprosthetic Bone Loss in Cementless Total Hip Arthroplasty Better Than Simvastatin

Round 1

Reviewer 1 Report

1. Original Submission

1.1. Recommendation

Major revision

2. Comments to Author:

Ms. Ref. No.: applsci-1855013

Title: Alendronate Prevents Early Periprosthetic Bone Loss in Cementless Total Hip Arthroplasty Better Than Simvastatin

Authors:

Dragos Apostu

Daniel Oltean-Dan, 

Alexandru Mester

Andrei Maxim

Adrian Bogdan Tigu

Horea Rares 

Ciprian Benea

Dan Cosma and Doina Piciu

 

 

Overview and general recommendation:

The article aims to compare the effect of alendronate and simvastatin in preventing early periprosthetic bone loss following the THA uncemented procedure. Authors explain that its use can lead to earlier weight-bearing in patients and reduce the rate of aseptic loosening. Forty-five patients undergoing cementless total hip arthroplasty were equally distributed into three groups: group I (alendronate), group II (simvastatin), and group III 30 (control). Alendronate statistically significantly increases the Bone Mineral Density at one month postoperatively compared to the control group in Gruen zones 5 and 6 (p=0.042 and p=0.039). Overall, the BMD was higher in the alendronate group compared to the control group at one month 37 postoperatively (p=0.043). The authors conclude that the study shows that alendronate administration following cementless total hip arthroplasty offers better protection against periprosthetic bone loss compared to simvastatin.

 

The topic seems of relative interest with publications in the literature concerning simvastatin and alendronate. Nonetheless, the scope is rather specific, and its relevance might be discussed, as most authors recommend full weight bearing following uncemented THA, in opposition to the authors. 

In highly osteoporotic patients, most surgeons might use cemented implants instead of uncemented, not for osteoporotic issues but mainly for fracture risk. 

The major downside of the study lies in its generalization limits to a total weight-bearing population. 

Moreover, systematic alendronate treatments are concerned with its possible side effects, which should be balanced to the benefit of bone mineralization and supposed bone osteointegration. The fact that mineralization affects the osteointegration of the THA is purely speculative and might be supported by bibliographic evidence.

The article got strong results and methodology, but postulates need to be much more explained, with heavier literature references and more conditional conclusions.

 

 

 

2.1. Major comments:

1. I would add the "osteoporotic patient" focus information in the abstract and introduction to clearly explain the aimed population of this study. The "non-weight bearing" might also be exposed clearly at these stages.

 

2. No side effects of Alendronate use are explained in the manuscript, it might be an interesting addition, and benefit/risk balance might also be discussed.

 

3. Because non-weight bearing is chosen in the population might be discussed and justified more deeply, more references are needed.

 

4. The principal limit of the work lies in the full weight bearing paradigm following THA, which is mainly recommended in the literature, in the study, the patients were not allowed to full weight-bearing for 6 weeks postoperatively, which might affect bone mineralization. This point limits the generalization of the results, only applying to a non-weight-bearing population after THA, and this point must be discussed further.

For example, this sentence is not conservative enough: "These results could encourage more orthopedic surgeons to allow early full-weight bearing in patients with cementless total hip arthroplasty, under the protection of alendronate or simvastatin". 

 

First, because most meta-analysis shows that there is no specific risk to full weight bearing, and mostly because with full weight bearing, the demineralization process around the stem might evolve differently than in a non-weight bearing population, 

 

shading the conclusions of the study.

 

5. There are too few references in this article; more robust publications focusing on weight bearing, mineralization, and osteointegration in high-impact orthopedic journals seem mandatory.

 

Mark miller M, Weiss T, Kreuz P, Rüter A, Konrad G. Partial weightbearing is not necessary after cementless total hip arthroplasty: a two-year prospective randomized study on 100 patients. Int Orthop. 2011 Aug;35(8):1139-43. DOI: 10.1007/s00264-010-

 

1089-2. Epub 2010 Jul 11. PMID: 20623280; PMCID: PMC3167435.

 

 

2.2. Minor comments:

1. Ref [1] is not rightly cited

Author Response

Dear Reviewer, first of all, we want to thank you for your thorough review of our manuscript. We consider that your valuable comments and recommendations give us the opportunity to increase the value of our manuscript. We have addressed the comments as follows:

 

Comment 1. I would add the "osteoporotic patient" focus information in the abstract and introduction to clearly explain the aimed population of this study. The "non-weight bearing" might also be exposed clearly at these stages.

Response: We have added „osteoporotic patient” and „non-weight bearing” information in both abstract and introduction sections

 

Comment 2. No side effects of Alendronate use are explained in the manuscript, it might be an interesting addition, and benefit/risk balance might also be discussed.

Response: The side effects of both alendronate and simvastatin have been added to the manuscript, and the benefit/risk balance has been added to the discussion chapter.

 

Comment 3. Because non-weight bearing is chosen in the population might be discussed and justified more deeply, more references are needed.

Response: The non-weight bearing protocol has been more intensively discussed and more references have been added.

 

Comment 4. The principal limit of the work lies in the full weight bearing paradigm following THA, which is mainly recommended in the literature, in the study, the patients were not allowed to full weight-bearing for 6 weeks postoperatively, which might affect bone mineralization. This point limits the generalization of the results, only applying to a non-weight-bearing population after THA, and this point must be discussed further. For example, this sentence is not conservative enough: "These results could encourage more orthopedic surgeons to allow early full-weight bearing in patients with cementless total hip arthroplasty, under the protection of alendronate or simvastatin". First, because most meta-analysis shows that there is no specific risk to full weight bearing, and mostly because with full weight bearing, the demineralization process around the stem might evolve differently than in a non-weight bearing population, shading the conclusions of the study.

Response: We have discussed the limitation of our study’s results to non weight bearing only patients in the Discussions chapter.

 

Comment 5. There are too few references in this article; more robust publications focusing on weight bearing, mineralization, and osteointegration in high-impact orthopedic journals seem mandatory.

Response: We have added 11 references to the manuscript centered on weight bearing, mineralization and osseointegration.

 

Comment 6. Ref [1] is not rightly cited.

Response: The references have bee updated and Ref [1] changed.

Author Response File: Author Response.docx

Reviewer 2 Report

Dear Authors:

interesting paper, on the line of Your research, and I would like to congratulate with You.

In my opinion, several limitations are present, and they shoud be better underlined:

- patients were not randomized, and groups were not comparable in terms of hyperlipidemia; this may imply some bias

- statistical power was not performed pre-operatively, so we cannot know the exact number of treated patient to be included into the study to

- post-op DEXA was not performed in a large percentage of patients (33% of group I, 20% of group II and III), so limiting the statistical analyis (loss of patients should be evaluated pre-op)

The strenght of the paper, on the other hand, in my opinion, relies on DEXA scan over all gruen's zones.

best regards,

Author Response

Dear Reviewer, first of all, we want to thank you for your review of our manuscript. We consider that your valuable comments and recommendations give us the opportunity to increase the value of our manuscript. We have addressed the comments as follows:

 

Comment 1: patients were not randomized, and groups were not comparable in terms of hyperlipidemia; this may imply some bias

Response: The comment is true. We have added the limitations to the Discussion chapter.

 

Comment 2: statistical power was not performed pre-operatively, so we cannot know the exact number of treated patient to be included into the study to

Response: We have added in the Materials and Methods sections the description of our statistical power analysis. We have used clincalc.com, and the data we used are from the following reference:

 

Nishioka T, Yagi S, Mitsuhashi T, Miyamoto M, Tamura T, Kobayashi T, Enishi T. Alendronate inhibits periprosthetic bone loss around uncemented femoral components. J Bone Miner Metab 2007, 25(3), 179-83.

 

Comment 3: post-op DEXA was not performed in a large percentage of patients (33% of group I, 20% of group II and III), so limiting the statistical analyis (loss of patients should be evaluated pre-op)

Response: Yes, it is true, the loss of patients has reduced to statistical power of our results, but the results still remained statistically significant. We also performed the Shapiro-Wilk test for normal distribution prior to applying the Student test. This limitation has been added to the discussion chapter.

 

Author Response File: Author Response.docx

Round 2

Reviewer 1 Report

Thank you for your revisions

Reviewer 2 Report

Dear Authors: thank You for Your integrations. In my opinion, no other revision is required. best regards,