# Effects of pentosan polysulfate sodium on joint structure and function out to six months in naturally-occurring canine osteoarthritis

**Authors:** Catherine J. M. Stapledon, Ravi Krishnan, Rachel A. Peat, Christian Reiter, Marjorie E. Milne, Stewart D. Ryan, Sebastien H. Bauquier, Thierry Beths

PMC · DOI: 10.1371/journal.pone.0342409 · PLOS One · 2026-02-10

## TL;DR

This study shows that pentosan polysulfate sodium improves joint pain, function, and cartilage in dogs with osteoarthritis for up to six months.

## Contribution

The study demonstrates the long-term disease-modifying potential of PPS in a canine model of osteoarthritis.

## Key findings

- PPS-treated dogs showed sustained pain reduction and improved gait symmetry for up to 26 weeks.
- PPS increased cartilage volume and slowed cartilage degradation compared to placebo.
- Biomarker changes in PPS-treated dogs suggest slowed osteoarthritis progression.

## Abstract

To evaluate the durability of effect and disease modification potential of a six-week course of pentosan polysulfate sodium (PPS) therapy out to 26 weeks (six months) in companion dogs with naturally-occurring osteoarthritis.

Twenty mixed-breed companion dogs were enrolled and randomized to receive either subcutaneous 3 mg/kg PPS injections (n = 14) or placebo (n = 6) once weekly for six weeks. Dogs underwent assessments for pain, functional gait analysis, MRI, and biomarker analysis at baseline and selected timepoints.

PPS treatment was well tolerated throughout the study. At baseline, the PPS-treated group had higher pain with Helsinki Chronic Pain Index (HCPI) scores of 15.14 compared to 8.83 in placebo. PPS-treated dogs experienced sustained HCPI reductions compared to placebo at 26 weeks after adjusting for differences in baseline pain. The PPS-treated group experienced normalization of gait symmetry up to week 26, indicating a reduction in lameness and an improvement in overall function. Total cartilage volume increased at weeks 8 and 26 from baseline in the PPS-treated group compared to placebo, and OA disease progression biomarker changes (CTX-I, HA, and TIMP-1) were consistent with slowed cartilage degradation at weeks 8 and 26.

PPS-treated dogs experienced improvements in pain, joint function, and cartilage volume compared to placebo, supported by changes in biomarkers at weeks 8 and 26. The 26-week timepoint in this translational canine model provides insights into the potential disease-modifying mechanisms and durability of PPS in long-term treatment outcomes in humans with OA.

## Linked entities

- **Chemicals:** HA (PubChem CID 854026)
- **Diseases:** osteoarthritis (MONDO:0005178)
- **Species:** Canis lupus familiaris (taxon 9615)

## Full-text entities

- **Genes:** TIMP1 (TIMP metallopeptidase inhibitor 1) [NCBI Gene 403816] {aka TIMP-1}
- **Diseases:** pain (MESH:D010146), Chronic Pain (MESH:D059350), OA (MESH:D010003), lameness (MESH:D007794)
- **Chemicals:** PPS (MESH:D010426)
- **Species:** Homo sapiens (human, species) [taxon 9606], Canis lupus familiaris (dog, subspecies) [taxon 9615]

## Full text

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## Figures

4 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12890089/full.md

## References

37 references — full list in the complete paper: https://tomesphere.com/paper/PMC12890089/full.md

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Source: https://tomesphere.com/paper/PMC12890089