ArticleTherapeutic advances in musculoskeletal disease2026
Cardiometabolic disease and risk of total knee arthroplasty among patients with knee osteoarthritis receiving intra-articular hyaluronic acid: a real-world cohort study.
Article in Therapeutic advances in musculoskeletal disease, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Background: Intra-articular hyaluronic acid (HA) is widely used in the management of knee osteoarthritis (OA); however, treatment responses vary substantially among patients. Cardiometabolic disease (CMD) has been increasingly recognized as a potential modifier of disease progression and treatment outcomes. This study aimed to evaluate the impact of cardiometabolic burden on clinically relevant outcomes in patients with knee OA receiving intra-articular therapy. Objectives: To evaluate the impact of cardiometabolic burden on clinically relevant outcomes in patients with knee OA receiving intra-articular therapy. Design: Real-world retrospective cohort study. Methods: We used the TriNetX Global Network to identify patients with knee OA who received intra-articular HA injections. CMD was defined as the presence of at least one cardiometabolic condition, including type 2 diabetes mellitus (T2DM), hypertension, or hyperlipidemia. Propensity score matching (1:1) was performed to balance baseline characteristics. The primary outcome was incident primary total knee arthroplasty (TKA) within 36 months. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazards models, and Kaplan-Meier analyses were performed to estimate cumulative incidence. Results: Among 50,833 eligible patients, 35,509 were classified into the CMD group and 15,324 into the control group. After propensity score matching, 14,220 patients remained in each cohort. Patients with CMD had a higher risk of TKA than controls at 12 months (HR 1.696, 95% CI 1.537-1.871), 24 months (HR 1.607, 95% CI 1.484-1.740), and 36 months (HR 1.598, 95% CI 1.485-1.720). Among individual cardiometabolic conditions, hypertension (HR 1.597, 95% CI 1.437-1.775) and hyperlipidemia (HR 1.373, 95% CI 1.184-1.594) were associated with increased TKA risk, whereas isolated T2DM was not significantly associated with TKA risk (HR 0.947, 95% CI 0.669-1.342). Kaplan-Meier analysis demonstrated lower TKA-free survival probabilities in the CMD group. Conclusion: CMD was associated with poorer clinical trajectories in patients with knee OA receiving intra-articular HA therapy. These findings suggest that metabolic health may be associated with treatment outcomes and may help identify patients at increased risk of progression to total knee arthroplasty.
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