Factors associated with knee pain at early stages of osteoarthritis

Objective: To investigate key risk factors associated with knee pain in early-stage osteoarthritis (OA).
Material and methods. The study included 109 women aged 35–75 years with knee pain lasting no more than one year and minimal radiographic changes (Kellgren–Lawrence grades 0–II). For each patient we filled in a personalized case form including anthropometric data, medical history, physical examination findings, pain and health status assessments using visual analog scale (VAS), and questionnaires (WOMAC, KOOS, DN4), along with information on comorbidities. All participants underwent standard knee radiography, ultrasound examination, and laboratory testing.
Results and discussion. One in six patients (15%) reported moderate or severe knee pain (≥40 mm on VAS). Patients with more intense pain were older than those with VAS <40 mm (median age 52.5 [42; 62.5] vs. 44 [38; 52] years; p=0.02) and had a higher body mass index (28 [25; 31.6] vs. 24 [21; 28] kg/m2; p=0.04). Statistically significant differences were also observed in OA severity: the high-pain group had higher WOMAC and all its components’ scores (median 1245 [872; 1510] vs. 248 [90; 410] mm; p<0.001), lower self-rated health status (60 [47; 80] vs. 29.5 [10; 50] mm; p<0.001), lower KOOS total scores and its components’ scores (44 [37; 67] vs. 79 [63; 88] %; p<0.001), and more frequent detection of synovitis on examination (50% vs. 19.3%; p<0.001) and in the past history (75% vs. 31.1%; p=0.008). Flexion restriction (50% vs. 19.3%; p=0.01), presence of osteophytes on ultrasound (50% vs. 10.75%; p<0.001), metabolic syndrome (56.25% vs. 25.8%; p=0.03), and postmenopausal status (68.75% vs. 35.48%; p=0.01) were also more frequent.
A discriminant model was developed to predict the risk of pain ≥40 mm on VAS, incorporating WOMAC functional limitations, presence of metabolic syndrome, ultrasound-detected osteophytes, and clinically significant synovitis. The model achieved an accuracy of 90.8%. Predictive performance was confirmed by ROC analysis (AUC=0.898, 95% CI 0.794–1.002), indicating high prognostic accuracy.
Conclusion. Severe knee pain at early stages of OA is associated with functional impairment according to WOMAC, clinical synovitis, ultrasounddetected osteophytes, and metabolic syndrome. These risk factors and the developed predictive model may be useful for planning individualized preventive and therapeutic strategies in OA patients.

1. GBD 2021 Osteoarthritis Collaborators. Global, regional, and national burden of osteoarthritis, 1990-2020 and projections to 2050: a systematic analysis for the Global Burden of Disease Study 2021. Lancet Rheumatol. 2023 Aug;5(9):e508-e522. doi: 10.1016/S2665-9913(23)00163-7.

2. Caneiro JP, O'Sullivan PB, Roos EM, et al. Three steps to changing the narrative about knee osteoarthritis care: a call to action. Br J Sports Med. 2020 Mar;54(5):256-258. doi: 10.1136/bjsports-2019-101328. Epub 2019 Sep 4.

3. Altman R, Asch E, Bloch D, et al. Development of criteria for the classification and reporting of osteoarthritis. Classification of osteoarthritis of the knee. Diagnostic and Therapeutic Criteria Committee of the American Rheumatism Association. Arthritis Rheum. 1986 Aug;29(8):1039-49. doi: 10.1002/art.1780290816.

4. Luyten FP, Denti M, Filardo G, et al. Definition and classification of early osteoarthritis of the knee. Knee Surg Sports Traumatol Arthrosc. 2012 Mar;20(3):401-406. doi:10.1007/s00167-011-1743-2.

5. Luyten FP, Bierma-Zeinstra S, Dell'Accio F, et al. Toward classification criteria for early osteoarthritis of the knee. Semin Arthritis Rheum. 2018 Feb;47(4):457-463. doi:10.1016/j.semarthrit.2017.08.006.

6. Migliore A, Scire CA, Carmona L, et al. The challenge of the definition of early symptomatic knee osteoarthritis: a proposal of criteria and red flags from an international initiative promoted by the Italian Society for Rheumatology. Rheumatol Int. 2017 Aug; 37(8):1227-1236. doi:10.1007/s00296-017-3700-y.

7. McAlindon TE, Cooper C, Kirwan JR, et al. Knee pain and disability in the community. Br J Rheumatol. 1992 Mar;31(3): 189-192. doi:10.1093/rheumatology/31.3.189.

8. Creamer P, Hochberg MC. The relationship between psychosocial variables and pain reporting in osteoarthritis of the knee. Arthritis Care Res. 1998 Feb;11(1):60-65. doi:10.1002/art.1790110110.

9. Verbrugge LM. Physical and social disability in adults. In: Hibbard H, Nutting PA, Grady ML, editors. Primary Care Research: Theory and Methods. RockvilleMD: Agency for Health Care Policy and Research, U.S. Department of Health and Human Services; 1991. P. 31–57.

10. Bidaut-Russell M, Gabriel SE. Adverse gastrointestinal effects of NSAIDs: consequences and costs. Best Pract Res Clin Gastroenterol. 2001 Oct;15(5):739-753. doi:10.1053/bega.2001.0232.

11. Altman RD, Gold GE. Atlas of individual radiographic features in osteoarthritis, revised. Osteoarthritis Cartilage. 2007;15 Suppl A: A1-56. doi:10.1016/j.joca.2006.11.009.

12. King LK, Mahmoudian A, Waugh EJ, et al. "You don't put it down to arthritis": A qualitative study of the first symptoms recalled by individuals with knee osteoarthritis. Osteoarthr Cartil Open. 2023 Dec 16;6(1): 100428. doi:10.1016/j.ocarto.2023.100428.

13. Cubukcu D, Sarsan A, Alkan H. Relationships between pain, function and radiographic findings in osteoarthritis of the knee: a crosssectional study. Arthritis. 2012;2012:984060. doi:10.1155/2012/984060

14. Okano T, Filippucci E, Di Carlo M, et al. Ultrasonographic evaluation of joint damage in knee osteoarthritis: feature-specific comparisons with conventional radiography. Rheumatology (Oxford). 2016 Nov;55(11): 2040-2049. doi:10.1093/rheumatology/kew304.

15. Abraham AM, Pearce MS, Mann KD, et al. Population prevalence of ultrasound features of osteoarthritis in the hand, knee and hip at age 63 years: the Newcastle thousand families birth cohort. BMC Musculoskelet Disord. 2014 May 19;15:162. doi:10.1186/1471-2474-15-162.

16. Nevalainen MT, Kauppinen K, Pylväläinen J, et al. Ultrasonography of the late-stage knee osteoarthritis prior to total knee arthroplasty: comparison of the ultrasonographic, radiographic and intra-operative findings. Sci Rep. 2018 Dec 10;8(1):17742. doi:10.1038/s41598-018-35824-3.

17. Koski JM, Kamel A, Waris P, et al. Atlasbased knee osteophyte assessment with ultrasonography and radiography: relationship to arthroscopic degeneration of articular cartilage. Scand J Rheumatol. 2016;45(2):158-164. doi:10.3109/03009742.2015.1055797.

18. Serban O, Porojan M, Deac M, et al. Pain in bilateral knee osteoarthritis – correlations between clinical examination, radiological, and ultrasonographical findings. Med Ultrason. 2016 Sep;18(3):318-325. doi:10.11152/mu.2013.2066.183.pin.

19. He ZJ, Li SL, Zou JH, et al. Pain-related risk factors among radiologic stages of knee osteoarthritis: data from the Osteoarthritis Initiative. Arthritis Care Res (Hoboken). 2023 Jun;75(6):1333-1339. doi:10.1002/acr.24997.

20. Abourazzak F, Talbi S, Lazrak F, et al. Does metabolic syndrome or its individual components affect pain and function in knee osteoarthritis women? Curr Rheumatol Rev. 2015;11(1):8-14. doi: 10.2174/1573397111666150522093337.

21. Sanchez-Lopez E, Coras R, Torres A, et al. Synovial inflammation in osteoarthritis progression. Nat Rev Rheumatol. 2022 May; 18(5):258-275. doi:10.1038/s41584-022-00749-9.