Abstract
Background/Aim: Osteoarthritis (OA) is a prevalent degenerative joint disease that significantly impacts quality of life, particularly when affecting the hands. However, whether patients with OA are associated with higher risk of developing upper limb disorders, specifically trigger finger (TF) and carpal tunnel syndrome (CTS), remains unclear. This study aimed to evaluate the risk of upper limb disease in OA patients. Patients and Methods: Using the US Collaborative Network, a subset of the TriNetX research network, we identified patients diagnosed with OA and matched them 1:1 with non-OA controls based on propensity scores. Matching covariates included age, sex, race, and comorbidities. The cohort consisted of 1,554,182 patients in each group. The hazard ratio of TF and CTS, as well as related surgical interventions, was assessed over a 5-year follow-up period. Results: Patients with OA had a 1.30-fold increased risk of TF [95% confidence interval (CI)=1.27-1.33] and a 1.50-fold increased risk of CTS (95%CI=1.48-1.53) compared to controls. The hazard ratios for undergoing surgical interventions were 1.61 for TF (95%CI=1.51-1.71) and 1.97 for CTS (95%CI=1.78-2.19). These risks remained significant across various sensitivity analyses and stratifications according to age and sex. Conclusion: OA significantly increases the risk of TF and CTS. These findings highlight the need for vigilant monitoring and management of upper limb disorders in OA patients to improve overall patient care and outcomes. Future research is warranted to focus on pathological mechanisms of OA and their impact on upper limb health to develop targeted interventions.
Osteoarthritis (OA) is a prevalent degenerative joint disease characterized by the breakdown of joint cartilage and underlying bone, most commonly affecting the hands, knees, hips, and spine. It leads to pain, stiffness, and impaired movement, significantly impacting the quality of life (1, 2). Among the various sites of OA, the involvement of upper limb joints, such as the carpometacarpal and interphalangeal joints, poses a substantial burden on daily activities (3). Notably, a large population study in Spain reported the prevalence of hand OA to be 2.4 per 1,000 person-years, indicating that this condition is more common than previously thought (4). Understanding the risk factors and associated conditions of OA is crucial for improving management and treatment strategies.
Trigger finger (TF) and carpal tunnel syndrome (CTS) are common upper limb disorders that affect hand function. TF, also known as stenosing tenosynovitis, is characterized by the catching or locking of a finger in a bent position due to inflammation and narrowing of the tendon sheath (5). CTS is caused by compression of the median nerve as it travels through the carpal tunnel in the wrist, leading to pain, numbness, and tingling in the hand and fingers (6). Both conditions can severely affect hand function and require medical or surgical intervention. Epidemiological studies have shown a 2.6% lifetime risk of developing TF, with higher incidence among individuals with systemic conditions, such as diabetes mellitus and inflammatory arthritis (7). While CTS and hand OA commonly coexist, CTS does not significantly impact the clinical signs or structural severity of the hand OA (8).
Previous studies have suggested a potential link between OA and upper limb disorders, but the relationship has not been thoroughly investigated (3, 8-10). Utilizing the TriNetX research network, a comprehensive global repository of de-identified electronic medical records, this study aimed to explore the association between OA and the risk of developing TF and CTS, as well as the likelihood of undergoing related surgical interventions. By leveraging a large-scale, real-world dataset, we aimed to provide robust evidence on the comorbidities and risk factors associated with OA, ultimately contributing to better clinical decision-making and patient care.
Patients and Methods
For the current research, we utilized one of the most extensive subsets within the TriNetX research network - the U.S. collaborative network. This network holds data from over 59 healthcare organizations across the United States. The data, which include claims, prescription records, lab results, and procedural statuses, were used for our in-depth analysis (11-14). This study followed the Declaration of Helsinki and was approved by the Institutional Review Board of ChiMei Medical Center (No.: 11212-E02).
Between January 1st, 2005, and December 31st, 2017, we enrolled patients diagnosed with osteoarthritis, constituting the osteoarthritis group. Individuals without osteoarthritis served as the non-osteoarthritis control group. For both groups, those who died before or after the index date, had a previous record of any cancer, had a previous record of upper limb diseases including trigger finger and carpal tunnel syndrome, or underwent any related surgical interventions before or on the index date, were excluded from the study population. To mitigate the potential influence caused by confounding bias, 1:1 propensity score matching was performed to determine the appropriate study population serving as control group. In the main analysis, covariates including age at index, sex, race, comorbidities, body mass index, substance abuse status and socioeconomic status were applied in the matching process. Outcome events included trigger finger, carpel tunnel syndrome and related surgical interventions. To improve internal validity, sensitivity analyses based on different algorithms of propensity score matching were performed. Moreover, sensitivity analyses applying different wash-out time periods were also performed. The periods were set as 12 months, 24 months and 36 months after the index date. Any outcome event occurred within this wash-out period would not be counted as valid outcome event. Stratification analyses were based on sex (male/female), age (18-64 years/65+), and osteoarthritis site (knee, hip, carpometacarpal, polyosteoarthritis). Definition of study population, covariates and outcome events were determined based on electronic medical records in the TriNetX research network (Table I). In this research, statistical analysis was performed using the Analytics tool within the TriNetX research network. Propensity score matching utilized a caliper set at 0.1. Hazard ratios for outcome events were calculated along with their corresponding 95% confidence intervals to assess significance.
Codes applied in TriNetX analytic systema.
Results
Before propensity score matching, the osteoarthritis group presented significant difference in age, substance use status, body mass index status, ambulatory visit status and comorbidity statuses including hypertension, diabetes mellitus, hyperlipidemia, and rheumatoid arthritis. Before matching, the mean age of the osteoarthritis group was 60.6 years, whereas the control group was 36.3 years. After 1:1 propensity score matching, 1,554,182 patients with osteoarthritis and the same number of non-osteoarthritis controls were identified (Figure 1). The differences in baseline characteristics became insignificant. The mean age of the osteoarthritis group was 57.2 years after matching. Within the osteoarthritis group, 56.9% of participants were female and 67.8% of participants were white people (Table II).
Patient selection flowchart.
Baseline characteristics of participants.
In the 5-year-follow-up period, the risk of people in osteoarthritis group being diagnosed with trigger finger and carpel tunnel syndrome was 1.30-fold (95%CI=1.27-1.33) and 1.50-fold (95%CI=1.48-1.53), respectively, while comparing with non-osteoarthritis controls. Regarding the hazard ratio of undergoing surgical intervention for trigger finger was 1.61 (95%CI=1.51-1.71) and the hazard ratio of undergoing surgical intervention for carpel tunnel syndrome was 1.97 (95%CI=1.78-2.19). The significance of upper limb disease risk remained in shorter follow-up time of 1-year and 3-year periods and sensitivity analyses applying different propensity score matching models and wash-out periods (Table III, Table IV and Table V). In stratification analysis, the increased risk of carpel tunnel syndrome and trigger finger in patients with osteoarthritis was statistically significant in each sex and age subgroups (Table VI). Male patients with osteoarthritis were associated with a 1.64-fold increased risk of carpal tunnel syndrome compared to controls (95%CI=1.60-1.69), while female osteoarthritis patients were associated with a 1.44-fold increased risk of carpal tunnel syndrome compared to controls (95%CI=1.41-1.47). The risk of patients older than 65 years old with osteoarthritis was 1.29-fold (95%CI=1.26-1.33) and 1.46-fold (95%CI=1.42-1.49) of the risk of having trigger finger and carpel tunnel syndrome, respectively. When stratified by osteoarthritis sites, the significance of upper limb diseases risk also remained (Table VII). For people with carpometacarpal osteoarthritis, the hazard ratio of developing future trigger finger and carpel tunnel syndrome was 3.31 (95%CI=3.07-3.57) and 3.08 (95%CI=2.90-3.27).
Risk of upper limb diseases under different follow-up timea.
Stratification analysis of age and sex.
Stratification analysis of osteoarthritis sitesa.
Sensitivity analysis: risk of upper limb diseases in osteoarthritis patients based on different covariate matching models, with 5-year follow up.
Sensitivity analysis: risk of upper limb diseases with different wash-out periodsa.
Discussion
The findings from this large-scale retrospective cohort study provide compelling evidence for the association between OA and increased risks of developing upper limb disorders, specifically TF and CTS. The results demonstrate that individuals with OA are at a significantly higher risk of both conditions compared to those without OA, even after adjusting for potential confounders through propensity score matching.
Several previous studies support the findings of our research (3). The study by Löfgren et al. highlights that diabetes mellitus is a significant risk factor for TF, showing a hazard ratio of 2.0 (95%CI=1.5-2.6) over a 20-year follow-up period (15). This aligns with our observation of increased risk for upper limb disorders in patients with OA, as comorbid diabetes mellitus is prevalent in this population. Moreover, the chronic inflammation and mechanical stress associated with OA may contribute to similar pathological processes in the tendons and nerves of the upper limb (16), potentially explaining the elevated risks of TF and CTS. The clustering of disease progression in multiple joints, as indicated in a study on hand OA, suggests a systemic predisposition to joint and tendon pathologies (3, 5). This supports our finding that patients with OA are more prone to developing TF and CTS. Furthermore, the association between musculoskeletal complications and diabetes, including an increased incidence of upper limb impairments, has been documented in multiple studies (7, 15). The role of chronic inflammation and mechanical stress in exacerbating tendon and nerve conditions in patients with OA is consistent with these observations.
Our study’s use of the TriNetX research network data ensures a robust and diverse sample, enhancing the generalizability of our findings. The comprehensive nature of the dataset, including claims, prescription records, laboratory data, and procedural status, allows for a detailed analysis of the comorbidities and outcomes associated with OA. Furthermore, the use of propensity score matching and sensitivity analyses adds rigor to our results, minimizing the impact of confounding factors. Moreover, the stratified analyses in our study revealed that the increased risks of upper limb disorders are consistent across different demographic groups, including sex and age subgroups. Notably, older patients with OA exhibited a higher risk of developing these conditions, emphasizing the need for early diagnosis and intervention. This finding is in line with the study by Dahlin et al., which reported a higher prevalence of TF in older individuals and those with comorbid conditions, such as diabetes and rheumatoid arthritis (9, 10).
Our research highlights the significant association between osteoarthritis and various hand disorders, including TF and CTS. While our results do not isolate the impact of carpometacarpal osteoarthritis alone, they indicate a broader relationship between OA and multiple hand conditions. Previous studies have shown that specific types of OA, such as basal thumb OA, are associated with higher incidences of upper limb disorders (9, 15). This suggests that future research should aim to more precisely identify the impacts of carpometacarpal osteoarthritis on hand health, providing a clearer understanding of its role and guiding targeted interventions. In spite of the strengths of this study, including a large sample size and the use of advanced statistical methods to control for confounding variables, several limitations should be acknowledged. The observational nature of the study precludes the establishment of causality between OA and upper limb disorders. Additionally, the reliance on electronic medical records may introduce information bias due to potential inaccuracies in data entry and coding (17). Moreover, in retrospective real-world study design, residual confounders could still exist and could potentially influence the onset of outcome events (18, 19). Future research should focus on elucidating the underlying mechanisms linking OA to these upper limb conditions and developing effective prevention and treatment strategies. By addressing these comorbidities, healthcare providers can offer more comprehensive care to individuals with OA, ultimately enhancing their overall well-being (3). This approach aligns with the findings of Bijsterbosch et al., who emphasize the importance of understanding and managing the broader impacts of OA to improve patient outcomes (1).
Conclusion
This study provides strong evidence that OA is associated with an increased risk of developing TF and CTS. Effective management of these conditions is vital for improving the life quality of patients with OA. Future research should focus on identifying the impacts of specific types of OA, such as carpometacarpal osteoarthritis, on upper limb health to guide targeted interventions. Such insights will help clinicians design more precise interventions, offering better support to OA sufferers. By further exploring the interplay between OA and upper limb disorders, we can advance prevention and therapeutic strategies, providing enhanced care for those affected by this widespread disease.
Footnotes
Authors’ Contributions
All the Authors were involved in drafting or revising the article and approved of the submitted version. Study conception and design: Su YJ and Gau SY. Data acquisition: Su YJ and Gau SY. Data analysis and demonstration: Su YJ and Gau SY. Initial draft preparation: Su YJ and Gau SY.
Funding
This study was granted by Chi-Mei Medical Center (CMFHR113018).
Conflicts of Interest
The Authors have no conflicts of interest to declare in relation to this study.
- Received May 20, 2024.
- Revision received June 17, 2024.
- Accepted June 18, 2024.
- Copyright © 2024 The Author(s). Published by the International Institute of Anticancer Research.
This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY-NC-ND) 4.0 international license (https://creativecommons.org/licenses/by-nc-nd/4.0).
