Pentosan Polysulfate Sodium: Repurposed for Osteoarthritis

Pentosan Polysulfate Sodium for Osteoarthritis

Pentosan polysulfate sodium is a repurposed drug for osteoarthritis may provide hope and relief who suffer from the pain and disability related to osteoarthritis.  Osteoarthritis is sometimes referred to as “wear and tear” arthritis distinguishing it from inflammatory arthritis like rheumatoid arthritis and its cousins.

Osteoarthritis by the Numbers

Osteoarthritis affects 33 million U.S adults including  nearly 14% over age 25 and 34% over age 65, but these numbers are a conservative estimate according to the CDC and don’t tell the whole story. It largely affects the weight bearing joints like hips and knees but also involves the shoulder and smaller joints of the hands and feet. Arthritis is the leading cause of disability in the US and it’s also expensive. People spend $2,600 in out-of-pocket expenses each year coping with their arthritis.

Treatments for Osteoarthritis

There is no cure for osteoarthritis. Traditional treatments for it include:

1. non steroidal anti-inflammatory drugs
2. physical therapy
3. braces and splints
4. corticosteroid injections
5. regenerative medicine interventions like platelet rich plasma (PRP) and stem cells.

All of these interventions have limitations, and with the exception of regenerative medicine interventions really do not address the problem of osteoarthritis at its very root, but they can all be effective in improving one’s ability to live with osteoarthritis and delay its inevitable progression.

As we stated in our previous post, there are 32,000 FDA approved generic drugs on the market that potentially can be repurposed to treat other medical problems. Pentosan polysulfate sodium is one of them that has potential in the management of  osteoarthritis?

What is Pentosan Polysulfate Sodium (PSS)?

Pentosan polysulfate sodium (PPS) is better known by its brand name which is Elmiron®. Elmiron® is FDA approved to treat bladder pain caused by interstitial cystitis. It is a heparin analogue and glycosaminoglycans derivative. PSS has been shown to be effective in the treatment of osteoarthritis. But has potential benefits beyond that which I will discuss downstream.

Pentosan polysulfate sodium is given orally when treating interstitial cystitis but administered subcutaneously (inject into fat tissue) when treating osteoarthritis. Zilosul is the brand name of PSS being used in Australia and the FDA has granted fast track application for use of PSS in the U.S. but can be obtained now through compounding pharmacies. The usual dose for osteoarthritis is 125 mg twice a week as opposed to 300 mg  used daily for management of interstitial cystitis.

When used long-term it can cause pigmentary maculopathy (retinal disease) which is dose related and more of concern with the long-term oral daily use of pentosan polysulfate sodium.

How Does Pentosan Polysulfate Sodium Work?

Pentosan polysodium sulfate works through various mechanisms of action. Pentosan polysulfate sodium inhibits NF-kB, which a key modulator of inflammation and in the process reduces the expression of pro-inflammatory cytokines: IL-1ß, IL-6, and TNF-α. PSS also reduces the expression of pain mediator nerve growth factor in the osteocytes of a degenerative joint. It inhibits enzymes that degrade joint cartilage, and it improves blood flow through anti-thrombotic activity (blood clot reducing activity).

Other actions of pentosan polysulfate sodium include the following:

• improves gut flora.
• reduces cancer growth due to its heparin-binding growth factor inhibitor.
• inhibits atherosclerosis in rats.
• decreases smooth muscle proliferation in benign prostate hypertrophy.
• has antiviral activity.
• improves dyslipidemia (high cholesterol).

All of these additional benefits makes PSS an exciting drug for repurpose in the management of osteoarthritis and beyond.

References 

CDC: Osteoarthritis. https://www.cdc.gov/arthritis/osteoarthritis/index.html

Sen, Rouhin; Hurley, John: Osteoarthritis. https://www.ncbi.nlm.nih.gov/books/NBK482326/

Liu X, Virk S, Fedorova T, Oo WM, Hunter DJ. The effect of pentosan polysulfate sodium for improving dyslipidaemia and knee pain in people with knee osteoarthritis: A pilot study. Osteoarthr Cartil Open. 2023 Feb 7;5(2):100343. doi: 10.1016/j.ocarto.2023.100343. PMID: 36879559; PMCID: PMC9985017.

Solanki P., et al. Repurposing pentosan polysulfate sodium as hyaluronic acid linked polyion complex nanoparticles for the management of osteoarthritis: a potential approach. Med. Hypotheses. 2021;157 doi: 10.1016/j.mehy.2021.110713.

Ghosh P., et al. Effects of pentosan polysulfate in osteoarthritis of the knee: a randomized, double-blind, placebo-controlled pilot study. Curr. Ther. Res. Clin. Exp. 2005;66(6):552–571. doi: 10.1016/j.curtheres.2005.12.012.

Ghosh P. The pathobiology of osteoarthritis and the rationale for the use of pentosan polysulfate for its treatment. Semin. Arthritis Rheum. 1999;28(4):211–267. doi: 10.1016/s0049-0172(99)80021-3

Smith MM, Melrose J. Pentosan Polysulfate Affords Pleotropic Protection to Multiple Cells and Tissues. Pharmaceuticals (Basel). 2023 March.

Smith, M.M.; Melrose, J. Xylan Prebiotics and the Gut Microbiome Promote Health and Wellbeing: Potential Novel Roles for Pentosan Polysulfate. Pharmaceuticals 2022.

Elliot SJ, Zorn BH, McLeod DG, Moul JW, Nyberg L, Striker LJ, Striker GE. Pentosan polysulfate decreases prostate smooth muscle proliferation and extracellular matrix turnover. Prostate Cancer Prostatic Dis. 2003;6(2):138-42. doi: 10.1038/sj.pcan.4500632. PMID: 12806372.