How to Prevent Aseptic Loosening in Cementless Arthroplasty: A Review

Round 1

Reviewer 1 Report

I would like to congratulate with the Authors for their research. I recommend the paper to be accepted for publication only after extensive revision, as in my opinion there are lot of "errors" that need to be addressed. here some of them:

1) a PRISMA flow chart is usually recommended to be published in meta-analysis and reviews

2) in the femoral stem nominated with long survival, some are cemented (Exeter, Charnley, Muller) while the paper is on uncemented prostheses

3) recent reviews (JAOOS or JBJS, Feb 2021) underline that cemented stems should be more used as less complications are present; this should be reported in this paper as well.

4) as for aseptic loosening, an importa role is played by the bearing surface, so its role should be better evaluated with regards to "new" X-linked UHMWPE and ceramics

5) in bearing surface, results of acetabular cups (nboth uncemented and cemented) are reported..

6) as for surgical technique, more variables exist and must be considered (high-volume surgeons, teaching hospital, senior surgeon of young surgeon, .. and so on..

7) and patient-related factors, I think the paper is well written. 

Author Response

Dear Reviewer 1,

Thank you for your comments on our manuscript. We admit that your comments and suggestions are very well sustained and will definitely help increase the scientific value of the manuscript. We have made the following changes to the manuscript:

1) a PRISMA flow chart is usually recommended to be published in a meta-analysis and reviews.

Answer: We have added a PRISMA flow-chart, as recommended (Figure 1).

2) in the femoral stem nominated with long survival, some are cemented (Exeter, Charnley, Muller) while the paper is on uncemented prostheses

Answer: We have removed the cemented femoral stems from the manuscript.

"According to a meta-analysis performed by Keurentjes et al., the lowest rate for aseptic loosening was found in the following stems: ABG I®, Osteonics Cementless®, R-B Interlok®, Zweymuller Alloclassic®, Freeman Cementless®, Stanmore Custom Mare®, MS-30®, Corail®  Profile Porous®, Bi-Metric®, Mallory-Head Cementless®, Taperloc®, Furlong®, CLS Spotorno® and Titan® [14]."

3) recent reviews (JAOOS or JBJS, Feb 2021) underline that cemented stems should be more used as less complications are present; this should be reported in this paper as well.

Answer: Unfortunately, we did not find the JAAOS or JBJS article in Feb 2021 regarding the complications of cemented vs. cementless stems. In the meanwhile, we have added the following sentence in the introduction chapter - "Nevertheless, there is still debate regarding the survivorship in cementless vs. cemented total hip replacements. A study on 170,413 THAs showed that cementless THAs had a higher risk of aseptic loosening compared to cemented THAs (RR=1,5) [1]."

4) as for aseptic loosening, an important role is played by the bearing surface, so its role should be better evaluated with regards to "new" X-linked UHMWPE and ceramics

Answer: We have added more data regarding the bearing surfaces.

"The micromotion between the acetabular cup and inlay produces wear debris which generate a biologic host response responsible for a periprosthetic bone loss that further leads to aseptic loosening [22].

     Ceramic-on-highly cross-linked polyethylene (CoPx) has the best survivorship (0.54/100-component-years), followed by metal-on-polyethylene according to New Zealand Joint Registry study performed on 106,139 THAs [23]. This result is according to another study by Hu et al. performed on 974 primary THAs [23]. Metal-on-metal bearings had the lowest survivorship (1.43/100-component-years) [23]. This statement is supported by a meta-analysis performed by Lee et al. in which metal on metal (MOM) was associated with a higher risk of revision compared to ceramic-on-ceramic (COC) bearing [24]. When comparing ceramic-on-polyethylene and ceramic-on-ceramic, a meta-analysis by Shang et al. on 2,702 patiens showed that the results are comparable in terms of revision rate at a long term follow-up [25]. On the other hand, an analysis of the Dutch Registry on 33,454 patients pointed out a higher 2-year cup revision rate in the ceramic-on-ceramic group compared to ceramic-on-polyethylene (HR=0.475) [26]. A study on 11,096 patients with primary THAs showed no difference at a 8.7 year follow-up in revision rates between ceramic-on-ceramic compared to metal-on-polyethylene [6]. On the contrary, on a follow-up of 20 years, ceramic-on-ceramic bearing had a lower rate of aaseptic revision rate compared to metal-on-polyethylene [27,28]. These studies suggest that the best bearing in terms of survivorship have the following order: ceramic-on-polyethylene, ceramic-on-ceramic, metal-on-polyethylene and metal-on-metal.

     Jaeger et al. tested three different locking mechanisms between the cup and inlay: Allofit®-S Alloclassic® with cross-linked Durasul®-PE liner (Zimmer Biomet); Pinnacle®-Multihole combinates with a cross-linked Marathon®-PE liner (DePuy Synthes) and Plasmafit® Plus7 with a conventional ultra-high-molecular-weight polyethylene (UHMWPE) liner (Aesculap) [20]. The micromotion was less in the Aesculap combination, followed by DePuy and Zimmer Biomet [22].

     Other UHMWPE have been recently introduced, with promising results, such as the X-linked UHMWPE, but further studies are needed in order to decide on the long-term effect on polyethylene wear and aseptic loosening."

5) in bearing surface, results of acetabular cups (nboth uncemented and cemented) are reported..

Answer: We have removed the cemented acetabular cups from the manuscript.

6) as for surgical technique, more variables exist and must be considered (high-volume surgeons, teaching hospital, senior surgeon of young surgeon, .. and so on..

Answer: We have added more variables such as surgeon volume and type of hospital. We did not find any studies regarding senior vs. young surgeons in the last 10 years. 

"5.1. Surgeon

     In terms of surgeon, a study on 116 low revision rate surgeons (<3.84% revision rate at 5 years) and 433 other surgeons, showed that low revision rate surgeons use fewer types of implants compared to the higher revision rate surgeons [28,29]. Moreover, the same study pointed out that lower revision rate surgeons were more likely to conduct more than 100 total hip replacements per year [29]. In terms of experience, lower revision rate surgeons were related to a higher experience in terms of years and cases per year, but the differences were subtle [29].

 

5.2. Hospital

     Regarding teaching-hospitals vs. non-teaching hospitals, it was proved that resident training does not influence the complication rate at a mean follow-up of 97 months [30]."

 

7) and patient-related factors.

Answer: we have added more data in the patient-related factors, especially in the demographics, obesity and smoking subchapters.

"

6.1. Demographics

     A study on 63,158 patients showed that when performing the surgery at the age of under 70 years old, the rate of revision is up to 35%, compared to 5% in the case of patients aged 70 years or older when performing the THA [37]. A study showed that female patients have a significantly increased periarticular remodeling (Ot.Lac.Ar = osteocyte lacunae area) compared to male patients in the samples retrieved during total hip replacement revision surgery [38]. On the other side, a systematic review showed that seven out of eight papers resulted in an increased risk for revision surgeries in male patients [39]."

"6.3.1. Obesity

     Obesity increases the overall risk of early revision of primary THAs due to aseptic loosening by 4.7 fold, as shown by Electricwala et al. on a study on 273 revision THAs [43]. Moreover, a study on 684 revision THAs showed that obesity increases the risk of early aseptic loosening in primary THAs to 30%, compared to 18% in nonobese patients, [44]. A meta-analysis by Haverkamp et al. including 15 studies, showed that obese patients have an odds ratio of 0.64 to develop aseptic loosening compared to nonobese patients [45]."

"6.4. Smoking

     It increases the risk for aseptic loosening by three times, as Lee et al. pointed out [37]. Bhaveen et al. showed that the overall implant survival of primary total hip arthroplasty at a mean follow-up of 51 months is 99% in the non-smoker group and 92% in the smoker group [58]. In addition, smoking cessation within two months before surgery does not add any benefits to the outcome of a THA according to a meta-analysis by Myers et al. [58]. Nevertheless, there was one randomized trial on 120 patients which showed that smoking cessation 6-8 weeks before surgery reduces the postoperative morbidity including wound-related complications and the need of a revision surgery [58,59]."

Reviewer 2 Report

Thank you for allowing me to review this interesting work.

It is a didactic review of how to prevent aseptic loosening in cementless TH arthroplasty. 

It gives original and deep insight into these last decade's critical points on this subject.

The work is well structured with a correct bibliography and recent references. 

 

1. Nonetheless, it lacks hindsight on various points, with a too simple approach (i.e., prosthesis designs, demographics, smoking...). More discussion following bibliographic listing might be needed by synthesizing critical information. Therefore, it would better distinguish fully admitted data, controversy, or contradictory results.

2. The M&M process for selecting interest references is too vague.

3. Most and foremost, the conclusion needs to be more incisive on recommendations. We do not find any suggestions in conclusion, as the title promise answers.

 

4. Specific points:

L.84: there is typo error "v"

l.205: "We already know that patients under the age of 55 are associated with a higher rate of aseptic loosening" is not consistent with table 1

L.210-220: "Obesity increases the risk of early revision due to aseptic loosening by 4.7 fold [34]. At five years postoperatively, the revision rate was as following: 25% for BMI=18-25; 38% 220 for BMI=25-30; 56% for BMI=30-35; 73% for BMI=35-40 and 75% for BMI>40."
These numbers need to be more detailed: they concern primary THAs referred for revision THA.

l.247: which outcome? what criteria? 

l.363-374 is not necessary

 

 

Despite interesting data and a well-structured manuscript, the review needs revisions to increase its value.

Author Response

Dear Reviewer 2,

Thank you for your comments on our manuscript. We admit that your comments and suggestions are very well sustained and will definitely help increase the scientific value of the manuscript. We have made the following changes to the manuscript:

1. Nonetheless, it lacks hindsight on various points, with a too simple approach (i.e., prosthesis designs, demographics, smoking...). More discussion following bibliographic listing might be needed by synthesizing critical information. Therefore, it would better distinguish fully admitted data, controversy, or contradictory results.

Answer: We have added new data to prosthesis design, demographics and smoking chapters. 

"4.1.3. Design

     Acetabular cups without screw holes have a lower rate of revision compared to ones with screw holes, as shown by Otten et al. in a study on 22,725 primary total hip replacements [12]. The authors showed that the rate of aseptic loosening was not statistically significant between the two, but a limitation of the study was a mean follow-up of only 3.4 years (0-18) [12]. On the other hand, randomized clinical trial on 100 patients showed no difference between solid cups and cluster hole cups at 10 years follow-up [13].

     Moreover, Keurentjes et al. performed a meta-analysis on the cumulative survival at 10 years to study the rate of aseptic loosening [14]. The following acetabular cups had the lowest rate of aseptic loosening, accordingly: Weber Hemispheric®, Trabecular Metal Monoblock Acetabular Component System®, JRI Threaded Cup®, Fitmore®, Conserve Plus®, Morscher Press Fit®, Zweymuller-Alloclassic Screw Cup®, Arthropor®, ACS Triloc+®, Titan® and Spectron® [14]."

"4.2.3. Design

     The femoral stems are divided into seven types, according to geometry, as following: type 1 (straight stem, single wedge), type 2 (straight stem, double wedge), type 3 (straight stem, tapered), type 4 (straight stem, cylindrical, fully coated, type 5 straight stem, (modular), type 6 (curved stem, anatomic stem) and type 7 (short stem) [19]. Type 1, type 2, type 6 and type 7 have an exclusively metaphyseal fixation, while types 3 and type 5 have a metaphyseal and diaphyseal fixation [19]. Type 4 has a primarily diaphyseal fixation. A study in 2011 by Khanujah et al. showed that types 1, 2, 4 and 7 femoral stems have better survival, as following: 98.8% at 17 years; 99.2% at 17 years, 97.9% at 15 years and 98.2% at 10 years, respectively [19]. Nevertheless, type 1, type. 2 and type 4 are associated with a higher rate of stress shielding and thigh pain [19]."

"6.1. Demographics

     A study on 63,158 patients showed that when performing the surgery at the age of under 70 years old, the rate of revision is up to 35%, compared to 5% in the case of patients aged 70 years or older when performing the THA [37]. A study showed that female patients have a significantly increased periarticular remodeling (Ot.Lac.Ar = osteocyte lacunae area) compared to male patients in the samples retrieved during total hip replacement revision surgery [38]. On the other side, a systematic review showed that seven out of eight papers resulted in an increased risk for revision surgeries in male patients [39]."

Regarding distinguishing between information, we have updated Table 1 and added a column in which the recommendations are considered "Generally accepted" or "Controversial".

       2. The M&M process for selecting interest references is too vague.

Answer: We have added data to the M&M process, as well as a PRISM chart.

"3. Materials and methods

     A systematic review of the MEDLINE database was performed for articles published between 2011 and 2021 containing the terms "loosening hip". We included meta-analysis, randomized controlled trials, reviews, and systematic reviews. The authors reviewed the abstract of each article and only English-written articles were considered. All studies involving preoperative, intraoperative and postoperative factors that affect aseptic loosening in cementless total hip arthroplasty were included. More specific, implant properties (design, material, bearing surfaces), surgical factors, patient-related factors (comorbidities, demographics, genetics, habits), postoperative protocol (activities, weight-bearing), use of perioperative drugs (antiosteoporotic drugs, opioids, statins, beta-blockers) were all included in our review. Studies on the aseptic loosening of both the acetabular component and the femoral stem were taken into account. Regarding the exclusion criteria, studies where only physiopathology, diagnosis or treatment of aseptic loosening were addressed were not included in our review. Moreover, only studies performed on cementless primary total hip replacements were included, while loosening of mega-prosthesis, hip revisions, hemiarthroplasties or hip resurfacing were not considered. The PRISMA flowchart is available in Figure 1."

     3. Most and foremost, the conclusion needs to be more incisive on recommendations. We do not find any suggestions in conclusion, as the title promise answers.

Answer: We have added the recommendations into the conclusion chapter.

"10. Conclusions

     Aseptic loosening is a complication that generates a lot of interest in the research community due to its importance. There are currently various methods by which the aseptic loosening rate can be reduced, such as implant characteristics, surgical technique, as well as patient-related and postoperative factors. As there has been a lot of research in the field of osseointegration and aseptic loosening, we consider that an update is important for the clinician to be able to use all of the available techniques to prevent this serious complication. Moreover, the data in this review paper could help researchers find new ways the treatment of aseptic loosening.

     A summary of the generally accepted recommendations include the use of trabecular metal acetabular cups, titanium alloy femoral stems, certain types of femoral stem design (types 1,2,4 and 7), ceramic-on-polyethylene bearing surfaces.

     Also, surgeons performing more than 100 THAs per year and are consistent with their implant type tend to have a lower revision rate. Surgical factors which limit aseptic loosening include lateral and posterior approaches, good implant stability, at least 60% of acetabular cup bone coverage and an inclination of around 45 degrees. Postoperatively, immediate full weight bearing is accepted.

     It is also important to inform on the higher risk of revision the patients with obesity, less than 70 years old, hyperglycemia, rheumatoid arthritis, avascular necrosis of the femoral head, hip dysplasia, sickle cell disease, Parkinson disease, chronic liver disease, lumbar spinal fusion, some genetic variations and a history of hip arthroscopy."

     4. Specific points:

L.84: there is typo error "v"

Answer: we have deleted the "v" error

l.205: "We already know that patients under the age of 55 are associated with a higher rate of aseptic loosening" is not consistent with table 1

Answer: We have made the changes in Table 1 accordingly.

L.210-220: "Obesity increases the risk of early revision due to aseptic loosening by 4.7 fold [34]. At five years postoperatively, the revision rate was as following: 25% for BMI=18-25; 38% 220 for BMI=25-30; 56% for BMI=30-35; 73% for BMI=35-40 and 75% for BMI>40."
These numbers need to be more detailed: they concern primary THAs referred for revision THA.

Answer: we have rewritten the "obesity" chapter for a better understanding. 

"6.3.1. Obesity

     Obesity increases the overall risk of early revision of primary THAs due to aseptic loosening by 4.7 fold, as shown by Electricwala et al. on a study on 273 revision THAs [43]. Moreover, a study on 684 revision THAs showed that obesity increases the risk of early aseptic loosening in primary THAs to 30%, compared to 18% in nonobese patients, [44]. A meta-analysis by Haverkamp et al. including 15 studies, showed that obese patients have an odds ratio of 0.64 to develop aseptic loosening compared to nonobese patients [45]."

l.247: which outcome? what criteria? 

Answer: we have rewritten the "smoking" chapter and added more data.

"6.4. Smoking

     It increases the risk for aseptic loosening by three times, as Lee et al. pointed out [37]. Bhaveen et al. showed that the overall implant survival of primary total hip arthroplasty at a mean follow-up of 51 months is 99% in the non-smoker group and 92% in the smoker group [58]. In addition, smoking cessation within two months before surgery does not add any benefits to the outcome of a THA according to a meta-analysis by Myers et al. [58]. Nevertheless, there was one randomized trial on 120 patients which showed that smoking cessation 6-8 weeks before surgery reduces the postoperative morbidity including wound-related complications and the need of a revision surgery [58,59]."

l.363-374 is not necessary

Answer: we have deleted lines 363-374.

Author Response File: Author Response.docx

Round 2

Reviewer 1 Report

Dear Authors: thank You for the review. I agree with this, and I recommend publication. best regards,

Author Response

Dear Reviewer,

Thank you for your comments and for your hard work which increased the value of the manuscript!

 

Respectfully,

The authors

Reviewer 2 Report

The modifications are fine, and the publication has improved its level. 

It only misses one critical aspect, I suggest the authors add a paragraph on dual mobility sockets as it is more and more widespread use in primary THA.

With this addition, the manuscript might be accepted.

Author Response

Dear Reviewer,

 

Thank you for your comments. We have added the paragraph on the dual mobility cups in the bearing surfaces section, as following:

"Another bearing which is gaining more and more interest in recent years is the dual mobility construct. A review which included 448 primary dual mobility cups at a mean follow-up of 7.6 years showed that aseptic loosening rate was less compared to unipolar group (OR=1.21, p=81) [29, 30]. Another study on 150 primary dual mobility THAs and 166 unipolar THAs at a mean follow-up of 31 months showed that dual mobility bearings had a lower rate of aseptic loosening (0.7% vs. 5%) [30]. An analysis of the Nordic Arthroplsaty Register Association on over 2,000 matched patients concluded that there was no difference in overall risk of revision between dual mobility cups and metal-on-polyethylene or ceramic-on-polyethylene bearings [31]. Another review on mid-term follow-up of more than 500 dual mobility cups showed that there was no statistically significant difference in aseptic loosening rates compared to unipolar cups [32]. A systematic review of Darrith et al. on more than 10,000 primary dual mobility cups resulted in an aseptic loosening incidence of 1.3% at a mean follow-up of 8.5 years [33]. The only long term study we found included 85 dual-mobility total hip replacements performed on obese patients and no aseptic loosening was found at a follow-up of 15 years [29,30]. More long-term follow-up studies are needed in order to properly assess the aseptic loosening rate."

 

We have also added the dual mobility cup in Table 1. 

 

Respectfully,

The authors