ArticlePloS one2015
Hyaluronic Acid Injections Are Associated with Delay of Total Knee Replacement Surgery in Patients with Knee Osteoarthritis: Evidence from a Large U.S. Health Claims Database.
Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 66 papers, 4 of them syntheses that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
66 citing papers in PubMed, 4 syntheses or guidelines pooled it, 145 citations in OpenAlex.
- Health Economic Assessments of Hyaluronic Acid Treatments for Knee Osteoarthritis: A Systematic Review.Advances in therapy · 2024Pooled it
- Intra-articular Hyaluronic Acid Treatments for Knee Osteoarthritis: A Systematic Review of Product Properties.Cartilage · 2023Pooled it
- One-year efficacy and safety of single or one to three weekly injections of hylan G-F 20 for knee osteoarthritis: a systematic literature review and meta-analysis.Clinical rheumatology · 2021Pooled it
- Consequences on Private Insurance Coverage: The AAOS Clinical Practice Guidelines and Hyaluronic Acid Injections.The Journal of bone and joint surgery. American volume · 2020Guideline
- Trial
- Platelet-rich plasma (PRP) in osteoarthritis (OA) knee: Correct dose critical for long term clinical efficacy.Scientific reports · 2021Trial
- Hyaluronan derivative HYMOVIS® increases cartilage volume and type ii collagen turnover in osteoarhritic knee: data from MOKHA study.BMC musculoskeletal disorders · 2019Trial
- Trial
- Beyond the Surgical Bill: Pharmacoeconomics and Real-World Utilization Across the Knee Osteoarthritis Care Pathway-A Critical Narrative Review.Healthcare (Basel, Switzerland) · 2026Review
- Long-term functional and clinical outcomes of intraarticular double-cross-linked high molecular weight hyaluronic acid (Crespine Gel Plus) injection in knee osteoarthritis: a one year prospective study.BMC musculoskeletal disorders · 2026Article
- Comparative Efficacy and Safety of Two Different Formulations of Linear Hyaluronic Acid in Patients with Knee Osteoarthritis.Pharmaceuticals (Basel, Switzerland) · 2025Article
- One shot of hyaluronic acid in advanced knee osteoarthritis: postmarketing clinical follow-up for real-world evidence in a pain unit.BMC musculoskeletal disorders · 2025Observational
- Enhancing the Therapeutic Potential of Human Umbilical Cord Mesenchymal Stem Cells for Osteoarthritis: The Role of Platelet-Rich Plasma and Extracellular Vesicles.International journal of molecular sciences · 2025Article
- Red Algae Alters Expression of Inflammatory Pathways in an OsteoarthritisPharmaceuticals (Basel, Switzerland) · 2025Article
- Efficacy and Safety of Intra-Articular Therapy with Cross-Linked Hyaluronic Acid in Patients with Knee Osteoarthritis.Pharmaceuticals (Basel, Switzerland) · 2025Article
- Factors influencing the decision to receive total knee replacement among patients with severe knee osteoarthritis under universal health insurance coverage.Scientific reports · 2024Article
- Beyond Boundaries of a Trial: Post-Market Clinical Follow-Up of SOYA Patients.Journal of clinical medicine · 2024Article
- Predictors of Satisfaction in Patients with Knee Osteoarthritis Treated with a Single Injection of Mannitol-Modified Crosslinked Hyaluronate Derivative.Journal of clinical medicine · 2024Article
- Article
- Limited Evidence to Support the Use of Intra-Articular Injection of Hyaluronic Acid for the Management of Hallux Rigidus: A Systematic Review.Foot & ankle orthopaedics · 2024Article
6 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issued
Authors and funding
4 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe growing prevalence of osteoarthritis (OA) and the medical costs associated with total knee replacement (TKR) surgery for end-stage OA motivate a search for agents that can delay OA progression. We test a hypothesis that hyaluronic acid (HA) injection is associated with delay of TKR in a dose-dependent manner. METHODS AND
findingsWe retrospectively evaluated records in an administrative claims database of ~79 million patients, to identify all patients with knee OA who received TKR during a 6-year period. Only patients with continuous plan enrollment from diagnosis until TKR were included, so that complete medical records were available. OA diagnosis was the index event and we evaluated time-to-TKR as a function of the number of HA injections. The database included 182,022 patients with knee OA who had TKR; 50,349 (27.7%) of these patients were classified as HA Users, receiving ≥1 courses of HA prior to TKR, while 131,673 patients (72.3%) were HA Non-users prior to TKR, receiving no HA. Cox proportional hazards modelling shows that TKR risk decreases as a function of the number of HA injection courses, if patient age, gender, and disease comorbidity are used as background covariates. Multiple HA injections are therefore associated with delay of TKR (all, P < 0.0001). Half of HA Non-users had a TKR by 114 days post-diagnosis of knee OA, whereas half of HA Users had a TKR by 484 days post-diagnosis (χ2 = 19,769; p < 0.0001). Patients who received no HA had a mean time-to-TKR of 0.7 years; with one course of HA, the mean time to TKR was 1.4 years (χ2 = 13,725; p < 0.0001); patients who received ≥5 courses delayed TKR by 3.6 years (χ2 = 19,935; p < 0.0001).
conclusionsHA injection in patients with knee OA is associated with a dose-dependent increase in time-to-TKR.
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