Does pentosan polysulfate (PPS) improve osteoarthritis?

Pentosan Polysulfate for Osteoarthritis: Limited Evidence for Efficacy

Based on current guidelines and available evidence, pentosan polysulfate sodium (PPS) is not recommended as a standard treatment for osteoarthritis due to insufficient high-quality evidence supporting its efficacy for improving clinical outcomes related to morbidity, mortality, and quality of life.

Current Guideline Recommendations for OA Management

The 2019 EULAR guidelines for hand osteoarthritis and the 2022 AAOS guidelines for knee osteoarthritis do not include pentosan polysulfate among recommended treatments 1. Instead, these guidelines recommend:

• First-line pharmacological therapy:

  • Acetaminophen/paracetamol (though with limited efficacy)
  • NSAIDs (oral or topical) for patients unresponsive to acetaminophen

• For symptomatic relief:

  • Chondroitin sulfate may be considered for hand OA 1
  • Intra-articular corticosteroid injections for acute pain exacerbations 1

Evidence Regarding Pentosan Polysulfate

The limited research on pentosan polysulfate for osteoarthritis shows:

1. A small open-label trial (n=20) from 2010 reported improvements in clinical assessments in patients with mild knee OA after 6 weekly subcutaneous injections of PPS 2. However, this study:

   • Had no control group
   • Used a small sample size
   • Was not blinded
   • Did not compare to standard treatments

2. Laboratory studies suggest potential mechanisms of action:

   • PPS may interact with cartilage matrix proteins 3
   • May have anti-inflammatory effects in animal models 4
   • Demonstrated some disease-modifying effects in experimental equine OA 5

Clinical Decision Algorithm

When considering treatment for osteoarthritis:

1. Start with non-pharmacological approaches:

   • Exercise, particularly strengthening quadriceps muscles
   • Weight loss for overweight/obese patients
   • Appropriate assistive devices (insoles, walking aids)
   • Patient education

2. For pharmacological management:

   • Begin with acetaminophen/paracetamol for mild pain
   • Progress to NSAIDs (oral or topical) if inadequate response
   • Consider intra-articular corticosteroid injections for acute flares

3. For patients seeking additional options:

   • Chondroitin sulfate may be considered for hand OA
   • Hyaluronic acid injections may benefit some patients, though evidence is inconsistent

4. For refractory cases:

   • Consider surgical options when appropriate (joint replacement for severe cases)

Important Caveats and Considerations

• PPS is not FDA-approved for osteoarthritis treatment in the United States
• PPS affects blood coagulation parameters 2, requiring monitoring if used
• The optimal dosing, route of administration, and treatment duration for OA remain undefined
• Most research on PPS for OA has been conducted in animal models or small human studies
• Current guidelines from major rheumatology and orthopedic organizations do not include PPS among recommended treatments

While some preliminary research suggests potential benefits of PPS for cartilage metabolism, larger randomized controlled trials comparing PPS to established treatments are needed before it can be recommended for routine clinical use in osteoarthritis management.