Osteoarthritis (OA) is a progressive joint disease that occurs as a result of the cartilage that cushions the bones wearing down over time. Currently, it is estimated that over 500 million people worldwide are affected by OA.  

Clinical OA studies have shown that when the condition is linked to metabolic syndrome, OA often results in more significant joint damage and overall disability. Additionally, these studies have also demonstrated a link between metabolic syndrome and OA, including a higher likelihood of dyslipidemia – an imbalance of lipids including cholesterol, low-density lipoprotein cholesterol, (LDL-C), triglycerides, and high-density lipoprotein (HDL).

In this single-arm, open-label, prospective, non-randomized pilot study, Liu et al. evaluated the efficacy and safety of pentosan polysulfate sodium (PPS) for dyslipidemia and knee OA-related symptoms. 

PPS has exhibited potential treatment benefits for OA in previous studies. Specifically, animal models have shown PPS to reduce cholesterol and triglyceride levels while also exhibiting anti-inflammatory properties. These studies have also demonstrated that PPS demonstrates properties that might be related to the treatment benefit for OA and dyslipidemia and could potentially improve plasma lipid levels, clinical assessments, and cartilage metabolism.

At the conclusion of this study, the authors observed a statistically significant decrease in LDL and a significant reduction in knee OA-related symptoms, including joint-related pain and stiffness.  

The findings of this study showed promising treatment effects of PPS for improving dyslipidemia and clinically observed symptoms related to knee OA (including knee pain, stiffness, and disability). Although this study found that PPS significantly reduced blood levels of total and LDL cholesterol in humans (a finding previously confirmed in animal models), the authors also pointed out that no significant change was found in the primary outcome of triglyceride levels.


While PPS, when administered in a dose of 10 mg/kg, was demonstrated to be safe and well tolerated, the authors point out that this was the first known study investigating the efficacy and safety of oral PPS in people with dyslipidemia and knee OA. 

Liu et al. also highlighted a few limitations of this study, including the small sample size of 38 participants which limited the interpretation of any treatment effect in the context of such variations. Other confounding factors identified in this study included various lifestyle changes that occurred over the course of the 26-week study.

The authors also pointed out that, while significant reductions in pain subscales were observed, the changes were similar in magnitude to changes observed over similar periods on the placebo arm of recent placebo-controlled knee OA pharmacological randomized clinical trials (RCTs).

To further validate the findings of this study, Liu et al. call for a larger RCT with an appropriate control group.

The authors conclude that oral treatment with PPS demonstrated treatment effects to improve dyslipidemia and clinical symptoms related to knee OA and that further studies in this area are necessary.

Source: The effect of pentosan polysulfate sodium for improving … – PubMed.” 7 Feb. 2023, https://pubmed.ncbi.nlm.nih.gov/36879559/.

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