Background: Celiac Disease (CD) is an autoimmune, gluten-sensitive enteropathy characterized by intestinal malabsorption and chronic inflammation. Its prevalence is increasing among patients undergoing total joint arthroplasty (TJA). The purpose of this study was to compare medical and surgical complications between patients with and without CD who undergo TJA.

Methods: Data from the PearlDiver Mariner 165 database from 2010 to 2022 was retrospectively analyzed to identify patients who underwent either total hip arthroplasty (THA) or total knee arthroplasty (TKA). Two cohorts were created based on CD status, with a 1:5 propensity match ratio for patients with and without CD. Both groups were matched for age, gender, rheumatoid arthritis, Charlson comorbidity index (CCI), smoking status, obesity, diabetes, chronic kidney disease, and joint arthroplasty type. A total of 23,459 patients were included in the study, comprising of 3,959 patients with CD and 19,500 non-Celiac patients. Both groups were evaluated for 90-day medical complications, 90-day readmissions, 2-year implant complications and healthcare reimbursements, using chi-square analysis and multivariate logistic regression analysis. 

Results: Celiac patients who underwent TJA had significantly increased incidences of deep vein thrombosis (0.58% vs. 0.28%; p=0.003), pulmonary embolism (0.43% vs. 0.24%; p=0.017), myocardial infarction (0.40% vs. 0.18%; p=0.006), and hypoglycemia (0.25% vs. 0.11%; p=0.030) within 90 days post-surgery. Multivariate analysis revealed that CD patients had significantly higher odds of implant complications, including aseptic loosening and revisions, compared to non-CD patients.

Conclusion: This retrospective study found that CD is associated with increased thromboembolic and other postoperative complications following TJA. Therefore, tailored postoperative management strategies, including a modified anticoagulant prophylaxis protocol, are needed for Celiac patients undergoing TJA to better manage these risks and improve patient outcomes.

Keywords: celiac disease, total joint arthroplasty, postoperative complications, thromboembolic events, implant complications

Total joint arthroplasty (TJA), including total hip arthroplasty (THA) and total knee arthroplasty (TKA), is a widely performed and highly effective surgical intervention for improving the quality of life in patients with degenerative joint diseases. Despite advancements in surgical techniques and perioperative care, postoperative complications remain a significant concern, particularly thromboembolic events, such as deep vein thrombosis (DVT) and pulmonary embolism (PE), which continue to pose serious risks to patient health and recovery. 

Celiac disease (CD), an autoimmune disorder affecting approximately 1% of the population, is characterized by gluten intolerance, and is primarily known for its gastrointestinal symptoms, including malabsorption and diarrhea.¹ However, recent research has highlighted the association between CD and systemic inflammation, as well as an increased risk of thrombotic events.^1,2 Although CD’s impact on venous thromboembolism has been noted in various medical contexts, its specific influence on postoperative outcomes following TJA has not been extensively studied. 

Given these observations, it is important to examine the risks associated with CD in the context of TJA. Preliminary evidence suggests that patients with CD may experience higher rates of thromboembolic events and other postoperative complications compared to those without CD.³ Therefore, the purpose of this study was to investigate medical, surgical, and hospital utilization outcomes in patients who have CD undergoing TJA.

This study utilized data from the PearlDiver Mariner 165 database (www.pearldiver.com; PearlDiver Technologies, Fort Wayne, Indiana, USA), encompassing records from January 1, 2010, to October 31, 2022. The database offers comprehensive longitudinal tracking of de-identified patients from various healthcare settings across the United States and includes Current Procedural Terminology (CPT) and International Classification of Diseases, Ninth and Tenth Revision (ICD-9 and ICD-10) codes for procedures and diagnoses. Patients who underwent total hip arthroplasty (THA) or total knee arthroplasty (TKA) during the study period were identified. Two cohorts were created based on the presence or absence of Celiac Disease (CD). The CD cohort consisted of patients with a documented diagnosis of CD prior to their operation, while the non-CD cohort included patients without this diagnosis. To control for potential confounders, a propensity score matching (PSM) technique was employed. Patients with CD were matched to non-CD patients at a 1:5 ratio based on the following variables: age, sex, type of arthroplasty (THA or TKA), obesity, tobacco use, and diabetes. This matching process aimed to ensure comparable baseline characteristics between the two cohorts.⁴

After propensity score matching, the study included a total of 23,459 patients who underwent TJA, comprising 3,959 patients diagnosed with CD and 19,500 non-CD patients. The propensity score matching was successful in ensuring well-balanced cohorts with similar baseline characteristics (Table 1). 

The primary outcomes of interest were the incidence of thromboembolic complications, including DVT, PE, and myocardial infarction (MI), within 90 days of TJA surgery. Secondary outcomes included hypoglycemic episodes and implant complications, such as aseptic loosening and the need for revision surgery. Descriptive statistics were used to summarize the baseline characteristics of the matched cohorts. Chi-square analysis and multivariate logistic regression analysis were performed using R software to evaluate the association between CD and postoperative complications. Odds ratios (OR) with 95% confidence intervals (CI) were calculated for each outcome. A p-value of <0.05 was considered statistically significant. In the PearlDiver database, values less than 11 are reported as <11 to maintain patient anonymity. This approach ensures that rare events cannot be traced back to individual patients, preserving confidentiality while allowing for robust data analysis.

The CD cohort demonstrated significantly higher incidences of several postoperative complications compared to non-CD patients. Within 90 days of surgery, patients with CD had significantly higher incidence rates of DVT (0.58 vs. 0.28%; P = 0.003), PE (0.43 vs. 0.24%; P = 0.017), MI (0.40 vs. 0.18%; P = 0.006), and hypoglycemic episodes (0.25 vs. 0.11%; P = 0.030) compared to non-CD patients.

Other complications, such as cerebrovascular accidents (CVA), venous thromboembolism (VTE), pneumonia (PNA), acute kidney injury (AKI), and surgical site infections (SSI), did not show significant differences between the groups, with incidence rates remaining similar across both cohorts (all p-values > 0.05).

Infectious and implant complications

There were no significant differences between CD and non-CD patients in terms of surgical site infections (SSI) (0.58% vs. 0.81%; P = 0.141). Similarly, the incidence of prosthetic joint infections (PJI) was comparable between the groups (1.16% vs. 1.47%; P = 0.133).

Additionally, CD patients showed significantly higher incidences of certain implant complications within two years of TJA. There were significantly increased rates of aseptic loosening (1.01% vs. 0.32%; P < 0.001), instability (1.97% vs. 0.38%; P < 0.001), and revision surgery (1.47% vs. 0.95%; P = 0.004) in the CD group (Table 2).

Logistic regression analysis

Logistic regression analysis identified a significant association between CD and several postoperative complications. Specifically, CD was associated with increased odds of DVT (OR 2.06, 95% CI [1.24-3.30], p=0.004), PE (OR 1.41, 95% CI [1.13-2.67], p=0.029), MI (OR 2.23, 95% CI [1.20-3.97], p=0.008), aseptic loosening (OR 3.18, 95% CI [2.12-4.73], p<0.001), and revisions (OR 1.53, 95% CI [1.13-2.05], p=0.005). No significant association was observed between CD and other complications, including CVA, PNA, AKI, hypoglycemic episodes, SSI, or 90-day ED visits (all p-values > 0.05) (Table 3).

This study provides critical insights into the relationship between Celiac Disease (CD) and postoperative outcomes following total joint arthroplasty (TJA). CD patients demonstrated significantly increased incidences of DVT, PE, MI, and hypoglycemic episodes, with incidence rates approximately double or more compared to non-CD patients. Moreover, CD patients faced a notably higher risk of implant-related complications, including aseptic loosening and revisions, highlighting another crucial area of concern in this patient population. These findings emphasize the considerable impact of CD on TJA outcomes and highlight the need for enhanced postoperative monitoring and management strategies for this patient population.⁵

The heightened risk of thromboembolic events among CD patients aligns with previous research showing an increased venous thromboembolism (VTE) risk in CD across various clinical contexts.^1,6 CD's association with systemic inflammation and altered coagulation pathways likely contributes to this elevated risk, as chronic immune activation may exacerbate clot formation in vulnerable patients.⁷ Additionally, nutrient malabsorption, including deficiencies in vitamin K, which plays a key role in coagulation, could be a factor. Our study reflects previous findings, underscoring the need for preoperative risk stratification and aggressive postoperative prophylactic anticoagulation strategies. 

Interestingly, our study found that CD patients also experience higher rates of aseptic loosening and implant revisions. This is particularly notable because it suggests that CD's impact extends beyond thromboembolic risk to biomechanical complications. A potential explanation may involve CD's underlying pathophysiology, characterized by chronic inflammation and malabsorption of essential nutrients, such as calcium and vitamin D, leading to impaired bone metabolism.⁸ This may lead to relatively weaker in-growth onto press fit implants in particular, leading to loosening and subsequent revision. Surgeons may want to have a lower threshold for cemented fixation in this patient population.

The absence of significant differences in infection rates between CD and non-CD patients contrasts with some studies that suggest increased infection susceptibility in CD patients.² [6]. This discrepancy may be attributed to differences in patient demographics, surgical techniques, perioperative care protocols, and possibly antibiotic regimens across studies. Variations in these factors, particularly in antibiotic use, could influence infection rates and may help explain the inconsistencies observed.

Ultimately, orthopaedic surgeons and perioperative care teams should recognize the increased thromboembolic risk in CD patients undergoing TJA, necessitating thorough preoperative screening and vigilant postoperative monitoring. Implementing more aggressive prophylactic anticoagulation strategies and ensuring closer follow-up care can help mitigate these risks. For example, extended thromboprophylaxis regimens or the use of particular anticoagulants might provide better protection against thromboembolic events.⁹ Evidence suggests that initiating prophylaxis earlier or extending its duration could be effective strategies.^10,11 Future research should aim to evaluate the efficacy of these strategies in CD patients to identify optimal prophylaxis regimens for reducing thromboembolic complications following TJA. 

Despite its strengths, this study has limitations inherent to its design and reliance on administrative data, which may lead to misclassification or underreporting of conditions and complications. The absence of detailed clinical information, such as specific surgical techniques, perioperative care protocols, and antibiotic regimens, restricts a comprehensive understanding of the mechanisms behind our observations. Furthermore, we were not able to match for postoperative anticoagulation, which if different between groups, could be a confounding variable. Nevertheless, this study offers valuable insights into the unique risks faced by CD patients undergoing TJA and highlights the need for tailored postoperative management strategies.

Our findings show that Celiac Disease is associated with a higher incidence of thromboembolic events and other postoperative complications, including aseptic loosening and implant revisions, following total joint arthroplasty. These complications may be driven by systemic inflammation, nutrient malabsorption, and altered coagulation pathways, underscoring the need for specialized postoperative management strategies to mitigate these risks and improve outcomes for CD patients. Moving forward, focused research on this patient population is essential to refine and optimize perioperative care protocols, including thromboprophylaxis and antibiotic regimens, ultimately ensuring safer and more effective surgical outcomes.

None.

The authors declare that there are no conflicts of interest.

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