# Serum Dkk-1 Is Associated with Pain Intensity, Flare-Ups, and Bone Mineral Density in Non-Obese Patients with Knee Osteoarthritis: A Single-Center, Cross-Sectional Study

**Authors:** Timea-Csilla Nagy-Finna, Árpád Sólyom, János Székely, Pál-István Kikeli, Erika-Lídia Szövérfi, Hunor Lukács, Anna-Lilla Faragó, Emőke Horváth, Horațiu Popoviciu, Előd Ernő Nagy

PMC · DOI: 10.3390/ijms27052216 · International Journal of Molecular Sciences · 2026-02-26

## TL;DR

This study found that serum DKK-1 levels are linked to pain and bone density in non-obese knee osteoarthritis patients.

## Contribution

The study identifies serum DKK-1 as a novel biomarker for pain and bone changes in non-obese knee osteoarthritis patients.

## Key findings

- Higher DKK-1 levels correlate with increased pain and flare-ups in non-obese patients.
- DKK-1 is associated with lower bone mineral density in knee osteoarthritis patients.
- Sclerostin, RANKL, and OPG levels were not significantly linked to pain or disease activity.

## Abstract

Osteoarthritis is the most common musculoskeletal disorder. It primarily affects people in their mid-40s and older. As the disease progresses, degenerative changes occur in the synovial membrane, subchondral bone, and cartilage. Ultimately, the entire joint and its surrounding tissues become structurally and functionally impaired. Several sets of biochemical markers have been proposed to enable timely diagnosis and anticipate disease progression. However, only a few of these markers are routinely used to evaluate disease activity in subgroups. We conducted a cross-sectional, single-center cohort study of 72 patients with knee osteoarthritis. Diagnoses were established based on clinical data and radiological findings. We examined two Wnt/β-catenin signaling inhibitors, serum DKK-1 and sclerostin, and two bone/cartilage metabolic regulatory factors, RANKL and OPG, correlating these with disease activity and pain scores (WOMAC, VAS, and KOFUS), radiographic stage, inflammatory molecules and indices, and bone mineral density. DKK-1 levels were higher in the intensive pain group (VAS > 5) and positively correlated with the KOFUS throughout the study. This correlation was stronger in individuals with a BMI < 30. Serum DKK-1 levels were higher in patients with lower bone mineral density. No significant modifications in SOST, RANKL, or OPG levels were found in any of the above settings. In our patient cohort with mild-to-moderate knee osteoarthritis (OA), sclerostin, osteoprotegerin (OPG), and receptor activator of nuclear factor kappa-B ligand (RANKL) were not related to pain or disease activity. In contrast, DKK-1 was an indicator of pain and low-grade flare-ups. Furthermore, DKK-1 was associated with the KOFUS and impaired bone turnover in non-obese subgroups. Confirming these relationships in larger groups of patients would contribute to more efficient use of DKK-1 in disease stratification algorithms.

## Linked entities

- **Proteins:** DKK1 (dickkopf Wnt signaling pathway inhibitor 1), TNFSF11 (TNF superfamily member 11), BTF3P11 (basic transcription factor 3 pseudogene 11)
- **Diseases:** osteoporosis (MONDO:0005298)

## Full-text entities

- **Genes:** DKK1 (dickkopf Wnt signaling pathway inhibitor 1) [NCBI Gene 22943] {aka DKK-1, SK}, TNFSF11 (TNF superfamily member 11) [NCBI Gene 8600] {aka CD254, ODF, OPGL, OPTB2, RANKL, TNLG6B}, CTNNB1 (catenin beta 1) [NCBI Gene 1499] {aka CTNNB, EVR7, MRD19, NEDSDV, armadillo}, TNFRSF11B (TNF receptor superfamily member 11b) [NCBI Gene 4982] {aka OCIF, OPG, PDB5, TR1}, SOST (sclerostin) [NCBI Gene 50964] {aka CDD, DAND6, SOST1, VBCH}
- **Diseases:** musculoskeletal disorder (MESH:D009140), Knee Osteoarthritis (MESH:D020370), inflammatory (MESH:D007249), Obese (MESH:D009765), impaired bone turnover (MESH:D001847), Pain (MESH:D010146), OA (MESH:D010003)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Full text

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## Figures

3 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12985288/full.md

## References

64 references — full list in the complete paper: https://tomesphere.com/paper/PMC12985288/full.md

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Source: https://tomesphere.com/paper/PMC12985288