Diabetes, Inflammatory Markers, and Tissue Thickness in Septic and Aseptic Hip Revision Surgeries

Introduction

Total hip arthroplasty (THA) is currently considered one of the most successful orthopedic surgical interventions, effectively relieving pain, increasing range of motion, and significantly improving overall quality of life in patients with severe degenerative, traumatic, or inflammatory hip joint pathologies [1]. Advances in surgical techniques and implant materials over the past 2 decades have substantially improved both short-term and long-term outcomes of THA, leading to a notable increase in its application among middle-aged and younger populations [2,3]. Particularly, younger patients with active lifestyles are increasingly undergoing primary hip arthroplasty, which consequently escalates the likelihood of future revision hip arthroplasty (RHA) procedures [4]. Projections indicate a 174% rise in primary THA demand by 2030, alongside a more than 2-fold increase in RHA procedures by 2026 [5]. Therefore, an in-depth analysis of RHA indications, surgical techniques, and associated complications is increasingly critical.

Revision hip arthroplasty (RHA) is often required for aseptic reasons, with aseptic loosening being the most frequent indication, followed by prosthetic dislocations, periprosthetic fractures, and, more rarely, fractures or deterioration of prosthetic components [6,7]. This condition results from the progressive loss of biological integration between the prosthetic components and the host bone, leading to osteolysis, implant migration, and mechanical instability over time [8]. Clinically, it manifests as persistent pain, functional limitations, and decreased mobility, often confirmed radiographically. Other aseptic indications such as prosthesis dislocation and periprosthetic fractures are typically related to mechanical or traumatic events, requiring timely surgical intervention [6,7]. Although the postoperative course in aseptic revisions tends to be more predictable, long-term success is still highly dependent on factors such as proper implant selection, accurate surgical technique, and patient adherence to rehabilitation protocols [7,8].

In contrast, septic RHA has a considerably more complex clinical scenario despite the lower incidence [6,9]. These cases demand a multidisciplinary approach due to the challenges in diagnosis and treatment. Effective management hinges on timely surgical intervention, appropriate antibiotic therapy, and careful consideration of patient-specific risk factors, including comorbidities such as diabetes mellitus (DM), which can compromise immune response and wound healing [9–12]. Diagnostic accuracy often requires a combination of laboratory analysis, advanced imaging, and microbiological or histopathological evaluation [11]. Septic revisions are associated with prolonged hospital stays, increased intraoperative blood loss, higher transfusion requirements, and greater risk of postoperative complications, all of which contribute to poorer long-term outcomes compared to aseptic cases [9–11].

Soft-tissue thickness has recently emerged as an important variable in revision hip arthroplasty, particularly in septic cases [13,14]. Thinner skin and compromised soft-tissue coverage can predispose patients to increased postoperative complications, such as wound healing difficulties and higher susceptibility to infections [15,16]. Evaluating soft-tissue thickness could therefore provide essential insights into individual patient risk profiles and aid surgeons in preoperative planning, potentially influencing surgical technique choices, wound management strategies, and postoperative care protocols. Despite its clinical significance, soft-tissue thickness remains relatively understudied in this context, highlighting the importance and novelty of its investigation.

A comparative analysis of septic and aseptic RHA patients provides valuable insights into respective risk factors, aiding surgical planning and postoperative care strategies. Investigating complications prevalent in septic cases, evaluating DM’s impact on infection control, and examining relationships between surgical duration, transfusion requirements, and clinical outcomes could significantly guide clinicians. Despite literature highlighting strengths and challenges in septic revision surgeries, variations in clinical approaches underscore the need for standardized data.

This study comparatively analyzed septic and aseptic RHA cases managed in our clinic between 2015 and 2020. By focusing on the clinical outcomes and risk factors associated with each type, including patient comorbidities and perioperative considerations, the findings are expected to enhance diagnostic accuracy, improve treatment strategies, and guide postoperative care, particularly in complex septic revision cases.

Material and Methods

DATA ANALYSIS:

Mean standard deviation, median, minimum, maximum, median, minimum, and maximum values are given in descriptive statistics for continuous data, and percentage values are given for discrete data. The normality of continuous variables was assessed using the Shapiro–Wilk test prior to the selection of statistical tests. For variables showing normal distribution, the independent samples t test was used; for those not normally distributed, the Mann-Whitney U test was applied. Chi-square and Fisher’s exact tests were used in group comparisons of nominal variables (cross-tabulations). Statistical analysis was performed using IBM SPSS for Windows version 20.0 (SPSS, Inc., Chicago, IL), and P<0.05 was accepted as the threshold for statistical significance.

Although the sample size (n=49) was relatively small, it reflects the entire population of patients who met the inclusion criteria and underwent revision hip arthroplasty in our center over a 5-year period. Due to the retrospective design, a formal power calculation was not conducted prior to data collection.

Ethics approval for the study was obtained from the relevant institutional ethics committee (approval date: 14.10.2024, Decision No: 2024/204, the Ethics Committee of Düzce University). The study was conducted in accordance with the principles of the Declaration of Helsinki. Since patient data were collected retrospectively, individual informed consent was not required. Patients’ identities were kept confidential, and personal information was anonymized.

Results

Demographic and clinical data of patients undergoing revision hip arthroplasty (RHA) were analyzed in detail. Age, sex, comorbidities, preoperative laboratory values, soft-tissue thickness, and surgical times were compared between aseptic and septic loosening groups. In addition, culture results, blood transfusion requirement, and mortality rates were evaluated. The statistical results obtained in the study are presented in detail in Tables 1–3. These findings help understand the effects of revision surgery with different indications on patient outcomes.

A total of 49 patients who underwent RHA were included in the study. The mean age was 60.4±9.5 years, and 67.3% were female. Right and left hips were almost equally affected. Most patients (87.8%) had at least 1 comorbidity, and 36.7% had diabetes mellitus (DM). At baseline, no statistically significant differences were observed between the septic and aseptic groups in terms of age, sex, side of surgery, or overall comorbidity (P>0.05), whereas DM was significantly more common in the septic group (66.7% vs 23.5%, P=0.004).

When the causes of loosening were analyzed, aseptic loosening was found in 69.4% and septic loosening in 30.6% of the patients. According to the preoperative Tönnis hip osteoarthritis classification, 55.1% of the patients were classified as grade 2, 36.7% as grade 3, and 4 patients (8.2%) had femoral neck fractures.

Revision surgery diagnoses were aseptic loosening in 36.7%, septic loosening in 30.6%, dislocation in 20.4%, periprosthetic fracture in 6.1% and protruded acetabular cup in 4.1%. Among the surgical interventions performed, 71.4% of patients underwent RTHA, 20.4% underwent RTKA after spacer removal, and 8.2% underwent acetabular cup revision only.

Microbiologic growth was detected in 28.1% (9 patients) of the patients cultured. According to the culture results, Methicillin-resistant Staphylococcus aureus (MRSA) was detected in 4 patients, Escherichia coli in 3 patients, Proteus mirabilis in 1 patient, and Enterobacter species in 1 patient, while no culture growth was observed in the other patients. The presence of MRSA and gram-negative pathogens such as E. coli and Proteus mirabilis indicates a high bacterial virulence in some cases, which may have contributed to the increased surgical complexity and inflammatory response observed in the septic group.

Table 1 shows that aseptic loosening was the most common reason for revision in patients who underwent RHA, with a high rate of comorbidity. Furthermore, the mortality rate of 8.2% indicates that this surgery carries a significant morbidity and mortality risk.

The distribution of revision surgery indications, previous surgical procedures, presence of diabetes mellitus, and initial osteoarthritis classification significantly differed between aseptic and septic groups, as illustrated in Figure 1.

Patients diagnosed with aseptic and septic loosening were compared in terms of demographic and clinical characteristics. No significant difference was found between the 2 groups in terms of age, sex, or and side distribution (P>0.05).

When comorbidities were analyzed, all patients in the septic loosening group had comorbidities, while this rate was 82.4% in the aseptic loosening group, but the difference was not statistically significant (P>0.05). The prevalence of DM was significantly higher in the septic loosening group (66.7% vs 23.5%, P=0.004).

There was no significant difference between the 2 groups in terms of loosening zones according to the preoperative Tönnis hip osteoarthritis classification, DeLee and Charnley/Gruen classifications at the first operation (P>0.05).

When the zones of loosening were compared between septic and aseptic groups, a statistically significant difference was found in DeLee zone 2 (P=0.040). This difference indicates that loosening was more common in DeLee zone 2 in absolute number of patients in aseptic cases. However, proportionally, the rate of loosening in DeLee zone 2 was higher in septic cases. In contrast, when the loosening in the femoral region was compared, no statistically significant difference was found in the Gruen zones (P>0.05).

According to the findings in Table 2, the frequency of DM was significantly higher in the septic loosening group. It also suggests that loosening in aseptic revisions, especially in DeLee zone 2, is more common than septic loosening. However, there was no statistically significant difference between the 2 groups in terms of age, sex, side distribution, presence of comorbidities, and loosening zones.

Preoperative and postoperative characteristics of aseptic and septic loosening groups were compared. Preoperative ESR and CRP values were significantly higher in the septic loosening group compared to the aseptic loosening group (P=0.002 and P=0.001, respectively). This finding supports the role of inflammatory markers as diagnostic indicators of infection in revision arthroplasty.

In terms of soft-tissue thickness, the soft-tissue thickness of the patients in the septic loosening group was significantly lower than in the aseptic loosening group (P=0.003). Although effect size could not be calculated due to the use of non-parametric statistics, the distributional difference between groups was substantial.

A significant difference was also observed between the groups in terms of the need for blood transfusion. The transfusion requirement was significantly higher in septic loosening patients compared to the aseptic loosening group (P<0.001, Cohen’s d=1.45). This suggests that septic revisions are associated with increased intraoperative blood loss and technical complexity.

The duration of revision surgery was significantly longer in the septic group compared to the aseptic group (P<0.00001, Cohen’s d=2.13). This reflects the increased surgical difficulty and intraoperative demands of managing infected cases. In addition, mortality rates were not significantly different between the 2 groups (P=0.576).

According to Table 3, inflammatory markers (CRP and ESR) were elevated, soft-tissue thickness was lower, and the need for blood transfusion was higher in the septic loosening group. However, there was no significant difference in surgical time and mortality rates between the 2 groups.

Discussion

In this study, patients who underwent RHA were analyzed in detail and significant differences were found between the aseptic and septic loosening groups. According to our findings, aseptic loosening was the most common indication for revision, while inflammatory markers (CRP and ESR), total revision surgery duration, and blood transfusion requirement were significantly higher in the septic loosening group, whereas soft-tissue thickness was markedly lower. In addition, the rate of DM was significantly higher in septic loosening patients and the rate of loosening in DeLee zone 2 was higher in the septic group. However, there was no significant difference between the 2 groups in terms of age, sex, or side distribution. These findings contribute to our understanding of the effect of revision surgery on patient outcomes and emphasize the importance of critical clinical parameters in the management of septic cases. This issue has been widely discussed in the literature due to its effects on clinical outcomes, and many studies have been conducted evaluating various approaches.

Biochemical tests are a useful screening method in the initial evaluation of patients with painful joint arthroplasty and planned revision surgery. In the literature, many studies have reported that these inflammatory markers (CRP and ESR) are significantly elevated in patients undergoing septic revision surgery [10–12,17]. In their meta-analysis, Huerfano et al (2017) reported that CRP and ESR values were significantly higher in patients with RHA compared to uninfected cases and that negative ESR and CRP values have an important role in excluding infection in RHA patients. Positive results of both tests are not specific for PJI because these values can be elevated in other foci of infection, neoplasia, or other inflammatory conditions; however, positive results of both tests increase the suspicion of prosthetic infection [18]. Our findings are consistent with these data and emphasize the importance of these parameters, which are clinically significant markers of inflammatory response in the septic process, in the diagnosis and follow-up process.

The comorbidities of patients in revision surgery significantly affect the risk of infection. In the literature, an American Society of Anesthesiologists (ASA) score above 2, uncontrolled DM and rheumatoid arthritis are among the factors that increase the risk of PJI [18]. In our study, the frequency of DM was significantly higher in the septic group. The fact that DM predisposes to chronic inflammation and impairs the immune response is considered an important risk factor for prosthetic infections. This finding is consistent with previous studies indicating DM as a major risk factor for PJI [19,20].

In the literature, significant differences in blood transfusion needs are observed depending on the indication for revision surgery. In the study by Tse et al (2020), increased blood transfusion requirement was found in patients undergoing septic total knee revision surgery, but this increase was not statistically significant [21]. Similarly, George et al (2017) found that the presence of infection in RHA increased the need for blood transfusion, but this alone was not an independent risk factor [22]. Palmer et al (2020) reported that the need for intraoperative transfusion was significantly higher in RHA performed due to infection compared to aseptic causes [23]. In the literature, increased need for blood transfusion in the septic revision group has been reported to be associated with prolonged surgical time, deterioration in soft-tissue quality, chronic inflammatory processes, and immune response changes in infected cases [24,25]. In our study, the blood transfusion requirement and total revision surgery duration were found to be significantly higher in septic cases compared to aseptic cases. This finding further highlights the technical challenges of septic revision surgery and the necessity of optimizing perioperative blood management strategies.

In our study, there was no significant difference in mortality rates between septic and aseptic groups. Lakomkin et al (2017) observed a mortality rate of 0.8% in patients with RHA [24], while Choi et al (2013) reported a mortality rate of 33% in septic RHA and 22% in aseptic RHA in patients with an average follow-up period of 5–6 years [26]. In our study, the overall mortality rate was 8.2%.

There are many reasons for revision surgery. In the literature, in a study of 439 THA patients who underwent revision over an 8 year period, aseptic loosening was reported as the most common reason for revision in 55%, followed by instability in 14% [7]. Similar results were found in the study by Ulrich et al (2008), where aseptic loosening was found in 51.9% and instability in 16.9% [27]. Bozic et al (2009) reported that the most common reasons for revision were instability/disclocation 22.5% and mechanical loosening 19.7% [28]. In our study, the most common reason for revision was aseptic loosening (38.8%), followed by septic loosening (30.6%).

In the literature, it has been reported that acetabular loosening occurs most frequently in DeLee and Charnley zone 1 [29–31]. Similarly, our study found that loosening was most commonly seen in zone 1. In addition, implant involvement in zone 2 was found to be statistically significantly higher in the septic group.

Dan et al (2006) reported that the greatest bone mineral density loss occurred in Gruen zone 7 [32]. Grappiolo et al (2021) reported that femoral loosening was most commonly observed in Gruen zones 1 and 7 [31], while Hochreiter et al (2020) found that bone mineral density loss occurred most prominently in Gruen zone 3 [33]. In our study, the most loosening was found in Gruen zones 1, 2, and 3.

Bozic et al (2009) reported the distribution of surgical procedures as 41.1% RTHA (the most common type of surgery), 13.2% femoral component revision, 12.7% acetabular component revision, 12.6% linear replacement, and 9.1% prosthesis removal [28]. Palmer et al (2020) reported that RTHA was 32.5%, femoral component revision only 25.5%, acetabular component revision only 15.7%, revision due to infection 17.1% and component exchange 4.7% [23]. In the study by Lakomkin et al (2017), the distribution of surgical procedures performed in patients with RHA was 23.9% for acetabular component revision only, 12.6% for femoral component revision only, and 63.5% for both femoral and acetabular component revision [24]. In our study, the most common surgical procedure was RTHA, with a rate of 69.2%.

A review by Heifner et al stated that it was recommended to use soft-tissue measurements instead of body mass ındex (BMI) in the prediction of postoperative complications [13]. Sprowls et al [14] found that increased lateral soft-tissue thickness was associated with increased likelihood of surgical site infection, deep infection, and revision in patients undergoing total hip arthroplasty, while Fernández et al [15] found a significant association between the risk of PJI after THA and radiographically measured soft-tissue thickness. In contrast to these studies, some studies in the literature did not find a significant relationship between peritrochanteric fat thickness and infection and wound complications after THA [16,34]. In our study, soft-tissue thickness values of patients with septic loosening were found to be lower than those with aseptic loosening. The results we obtained in RHA cases contradict the existing literature. This may be due to the small number of relevant studies in the literature and the fact that previous hip arthroplasty studies mainly included primary THA cases. This suggests that soft-tissue thickness is affected by different factors in primary and revision cases. The literature shows that the presence of infection causes an increase in proinflammatory cytokine levels in soft tissue, which in turn triggers the lipolysis process in adipose tissue [35]. Therefore, in primary cases, low soft-tissue thickness is a factor affecting infection, whereas in revision cases, this may occur as a result of the presence of infection. These findings suggest that monitoring soft-tissue thickness may not only aid in infection surveillance but also reflect ongoing tissue catabolism in chronic infection. Therefore, integrating soft-tissue thickness evaluation, especially in revision candidates with other clinical and laboratory markers, could enhance preoperative risk stratification and postoperative management.

One of the most important limitations of this study is its single-center, retrospective design. The relatively small number of patients may limit the generalizability of the data obtained. In addition, soft-tissue thickness was measured only from radiographs, which resulted in the inability to distinguish soft-tissue components and to make direct physical measurements. Moreover, no formal matching or statistical adjustment was performed for potential confounders such as age, BMI, and comorbidities, which may have influenced the outcomes. Additionally, due to the retrospective design, causal relationships cannot be definitively established. Effect sizes were calculated for key variables; however, a priori power analysis was not conducted due to the retrospective design and limited sample size. The fact that studies on the relationship between infection and soft-tissue thickness have largely focused on knee arthroplasty suggests that more research on hip arthroplasty is needed. Prospective and multicenter studies in larger patient groups will contribute more definitive results on this subject. In particular, future studies should aim to determine whether reduced soft-tissue thickness is a predisposing factor or a consequence of infection in revision hip arthroplasty. Incorporating advanced imaging techniques and histopathological evaluations may provide a better understanding of the underlying mechanisms.

Conclusions

This study examined the clinical and radiological differences between septic and aseptic loosening in patients undergoing revision hip arthroplasty. Our results showed that inflammatory markers were significantly elevated, operative times and blood transfusion requirements were higher, and diabetes mellitus was more prevalent in septic cases. Most notably, soft-tissue thickness was found to be lower in infected cases, contrary to prior literature on primary hip arthroplasty. This finding suggests that, in revision cases, soft-tissue thinning may be a consequence of chronic infection rather than a predisposing factor.

Given the retrospective design and limited sample size, these findings should be interpreted with caution. However, they underscore the importance of evaluating soft-tissue status, systemic comorbidities, and inflammatory parameters during clinical decision-making. Future prospective studies should aim to confirm these findings and determine whether reduced soft-tissue thickness could be used as a diagnostic marker or is a result of chronic infection, potentially guiding preoperative risk stratification and postoperative care.