Background: While assessing symptomatic and structural outcomes in knee osteoarthritis (KOA) is common, the distinction between unilateral and bilateral KOA is less explored. Because pain reporting by subjects with bilateral KOA may be confounding for pain reports of a single joint, some newer trials choose to impose restrictions for the symptoms of the non-target knee [1-3]. The presence of multi-joint OA may reflect a more systemically driven and possibly more progressive OA phenotype that could be differing from single-joint disease. In organ diseases such as those affecting the heart, lungs, and kidneys, organ damage is the most critical parameter for function decline and mortality. Intuitively, this concept might also apply to OA, where generalized disease severity could relate to progression. However, details of differences between uni- or bilateral OA patients in terms of their typical baseline characteristics and longitudinal outcomes are not well described.

Objectives: The primary goal of this analysis is to explore differences in baseline demographics and structural progression risks between unilateral and bilateral KOA.

Methods: The current data is based on a post-hoc analysis of two phase III, randomized, double-blind, placebo-controlled studies where a total of 2206 participants were randomized 1:1 to oral salmon-calcitonin (0.8 mg twice daily) or placebo and followed for 24 months.

For this post-hoc analysis we grouped participants into unilateral KOA or bilateral KOA based on radiological and symptomatic criteria, where KOA was defined as Kellgren-Lawrence (KL)-grade ≥2 and baseline Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain ≥30 out of 100. As per trial inclusion criteria, all participants had radiographic and symptomatic KOA of the target knee. Baseline demographics were summarized and tested with two-sample t-test for quantitative data and Fisher’s exact test for categorical data. Risk for target-knee structural progression in KL-grade and joint space width (JSW) as change from baseline to year 2 were analyzed using risk ratio and ANCOVA. Correction for multiple testing was done with Bonferroni-Holm.

Results: KL grade (and WOMAC pain) was obtained for 2184 (2119) participants at randomization, and 1473 (1441) participants at end of study. For baseline demographics see Table 1.

This analysis identified several significant differences in baseline demographics between participants with unilateral and bilateral KOA. Participants with bilateral KOA were more likely to be female, older, have a higher BMI, and have greater target knee baseline pain compared to those with unilateral KOA. There were no differences in race and target knee baseline KL-grade.

There were no differences in structural knee progression as measured with KL-grade or JSW between participants with unilateral and bilateral KOA. See Table 2.

Conclusion: We found that patients with bilateral KOA were more likely to be female, older, have a higher BMI, possibly suggesting a more generalized OA, that also was associated with greater target knee baseline pain compared to those with unilateral KOA. There were no observed differences in terms of risk of structural progression based on uni- or bilateral KOA, which suggest that the general KOA disease activity is not higher in patients with more affected knee joints.

REFERENCES: [1] Riddle DL, Stratford PW. Unilateral vs bilateral symptomatic knee osteoarthritis: associations between pain intensity and function. Rheumatology. 2013 Dec 1;52(12):2229–37.

[2] Yazici Y, McAlindon TE, Gibofsky A, Lane NE, Clauw D, Jones M, et al. Lorecivivint, a Novel Intraarticular CDC‐like Kinase 2 and Dual‐Specificity Tyrosine Phosphorylation‐Regulated Kinase 1A Inhibitor and Wnt Pathway Modulator for the Treatment of Knee Osteoarthritis: A Phase II Randomized Trial. Arthritis & Rheumatology. 2020 Oct 6;72(10):1694–706.

[3] Bihlet AR, Byrjalsen I, Andersen JR, Öberg F, Herder C, Bowes MA, et al. Symptomatic and structural benefit of cathepsin K inhibition by MIV-711 in a subgroup with unilateral pain: post-hoc analysis of a randomised phase 2a clinical trial. Clin Exp Rheumatol. 2022 May;40(5):1034–7.

Acknowledgements: NIL.

Disclosure of Interests: Jakob Mejdahl Bentin: None declared, Morten Karsdal Nordic Bioscience, Nordic Bioscience, Asger R. Bihlet: None declared.

© The Authors 2025. This abstract is an open access article published in Annals of Rheumatic Diseases under the CC BY-NC-ND license ( http://creativecommons.org/licenses/by-nc-nd/4.0/ ). Neither EULAR nor the publisher make any representation as to the accuracy of the content. The authors are solely responsible for the content in their abstract including accuracy of the facts, statements, results, conclusion, citing resources etc.