Research progress on the correlation between gender differences and the incidence of knee osteoarthritis_West China Medical Journal

Authors：

LIU Linfeng ¹ , HU Xiaoshen ² , SHI Pengbo ³ ,  WANG Lihe ³

1. College of Orthopedics and Traumatology, Henan University of Chinese Medicine, Zhengzhou, Henan 450046, P. R. China;
2. Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan 611137, P. R. China;
3. Department of Orthopaedics and Traumatology, the First Affiliated Hospital of Henan University of Chinese Medicine, Zhengzhou, Henan 450003, P. R. China;

Corresponding author：

WANG Lihe, Email: wanglihe0222@sina.com

Keywords：

Knee osteoarthritis; gender differences; pathogenesis; research progress

DOI：

10.7507/1002-0179.202310201

Video：

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Knee osteoarthritis (KOA) is one of the common degenerative joint diseases, which is more common in the middle-aged and elderly population. It shows significant gender differences, with a significantly higher incidence rate in women than in men, seriously affecting the quality of life of patients. However, there are few research reports on the correlation between gender differences and the incidence of KOA both domestically and internationally. Therefore, this article will summarize and analyze the potential causes of gender differences related to the incidence of KOA from five aspects: hormone levels, anatomical biomechanical characteristics, genes, obesity, and exercise-muscle factors. Through a comprehensive review of research progress, the aim is to provide a theoretical basis for gender based personalized treatment of KOA in clinical practice.

Citation： LIU Linfeng, HU Xiaoshen, SHI Pengbo, WANG Lihe. Research progress on the correlation between gender differences and the incidence of knee osteoarthritis. West China Medical Journal, 2024, 39(4): 649-653. doi: 10.7507/1002-0179.202310201 Copy

1.	Katz JN, Arant KR, Loeser RF. Diagnosis and treatment of hip and knee osteoarthritis: a review. JAMA, 2021, 325(6): 568-578.
2.	Sharma L. Osteoarthritis of the knee. N Engl J Med, 2021, 384(1): 51-59.
3.	Cui A, Li H, Wang D, et al. Global, regional prevalence, incidence and risk factors of knee osteoarthritis in population-based studies. EClinicalMedicine, 2020(29/30): 100587.
4.	Srikanth VK, Fryer JL, Zhai G, et al. A meta-analysis of sex differences prevalence, incidence and severity of osteoarthritis. Osteoarthritis Cartilage, 2005, 13(9): 769-781.
5.	Szilagyi IA, Waarsing JH, van Meurs JBJ, et al. A systematic review of the sex differences in risk factors for knee osteoarthritis. Rheumatology (Oxford), 2023, 62(6): 2037-2047.
6.	Dong Y, Yan Y, Zhou J, et al. Evidence on risk factors for knee osteoarthritis in middle-older aged: a systematic review and meta analysis. J Orthop Surg Res, 2023, 18(1): 634.
7.	Szilagyi IA, Waarsing JH, Schiphof D, et al. Towards sex-specific osteoarthritis risk models: evaluation of risk factors for knee osteoarthritis in males and females. Rheumatology (Oxford), 2022, 61(2): 648-657.
8.	Hanna FS, Teichtahl AJ, Wluka AE, et al. Women have increased rates of cartilage loss and progression of cartilage defects at the knee than men: a gender study of adults without clinical knee osteoarthritis. Menopause, 2009, 16(4): 666-670.
9.	Li D, Li S, Chen Q, et al. The prevalence of symptomatic knee osteoarthritis in relation to age, sex, area, region, and body mass index in China: a systematic review and meta-analysis. Front Med (Lausanne), 2020, 7: 304.
10.	Pang H, Chen S, Klyne DM, et al. Low back pain and osteoarthritis pain: a perspective of estrogen. Bone Res, 2023, 11(1): 42.
11.	Emmanuelle NE, Marie-Cécile V, Florence T, et al. Critical role of estrogens on bone homeostasis in both male and female: from physiology to medical implications. Int J Mol Sci, 2021, 22(4): 1568.
12.	牟利民, 张文豪, 张思平, 等. 绝经后女性退变性膝骨关节炎疼痛与性激素水平及关节液炎性因子的相关性研究. 中国全科医学, 2022, 25(29): 3652-3657.
13.	Gilmer G, Bean AC, Iijima H, et al. Uncovering the “riddle of femininity” in osteoarthritis: a systematic review and meta-analysis of menopausal animal models and mathematical modeling of estrogen treatment. Osteoarthritis Cartilage, 2023, 31(4): 447-457.
14.	Hanna FS, Wluka AE, Bell RJ, et al. Osteoarthritis and the postmenopausal woman: epidemiological, magnetic resonance imaging, and radiological findings. Semin Arthritis Rheum, 2004, 34(3): 631-636.
15.	Lou C, Xiang G, Weng Q, et al. Menopause is associated with articular cartilage degeneration: a clinical study of knee joint in 860 women. Menopause, 2016, 23(11): 1239-1246.
16.	Xu X, Li X, Liang Y, et al. Estrogen modulates cartilage and subchondral bone remodeling in an ovariectomized rat model of postmenopausal osteoarthritis. Med Sci Monit, 2019, 25: 3146-3153.
17.	Jung JH, Bang CH, Song GG, et al. Knee osteoarthritis and menopausal hormone therapy in postmenopausal women: a nationwide cross-sectional study. Menopause, 2018, 26(6): 598-602.
18.	Liu Y, Zhang M, Kong D, et al. High follicle-stimulating hormone levels accelerate cartilage damage of knee osteoarthritis in postmenopausal women through the PI3K/AKT/NF-κB pathway. FEBS Open Bio, 2020, 10(10): 2235-2245.
19.	刘亚平. 卵泡剌激素对绝经后女性膝骨关节炎软骨损伤的影响及机制研究. 济南: 山东大学, 2020.
20.	Sasaki E, Chiba D, Ota S, et al. Reduced serum levels of anti-Mullerian hormone is a putative biomarker of early knee osteoarthritis in middle-aged females at menopausal transition. Sci Rep, 2021, 11(1): 4931.
21.	Rowe E, Beauchamp MK, Astephen Wilson J. Age and sex differences in normative gait patterns. Gait Posture, 2021, 88: 109-115.
22.	Phatama KY, Isma S, Devi LK, et al. Relationship of anterior knee pain with quadriceps angle and anthropometric measurements in an asian female population. Malays Orthop J, 2022, 16(2): 95-101.
23.	Sharma R, Vaibhav V, Meshram R, et al. A systematic review on quadriceps angle in relation to knee abnormalities. Cureus, 2023, 15(1): e34355.
24.	Kerrigan DC, Todd MK, Della Croce U. Gender differences in joint biomechanics during walking: normative study in young adults. Am J Phys Med Rehabil, 1998, 77(1): 2-7.
25.	Lu Y, Zheng ZL, Lv J, et al. Relationships between morphological changes of lower limbs and gender during medial compartment knee osteoarthritis. Orthop Surg, 2019, 11(5): 835-844.
26.	Ro DH, Lee DY, Moon G, et al. Sex differences in knee joint loading: cross-sectional study in geriatric population. J Orthop Res, 2017, 35(6): 1283-1289.
27.	Zhang Y, Yang Y, Wang C, et al. Identification of diagnostic biomarkers of osteoarthritis based on multi-chip integrated analysis and machine learning. DNA Cell Biol, 2020: 16.
28.	Zhong J, Xiang D, Ma X. Prediction and analysis of osteoarthritis hub genes with bioinformatics. Ann Transl Med, 2023, 11(2): 66.
29.	Hame SL, Alexander RA. Knee osteoarthritis in women. Curr Rev Musculoskelet Med, 2013, 6(2): 182-187.
30.	Li C, Zheng Z. Cartilage targets of knee osteoarthritis shared by both genders. Int J Mol Sci, 2021, 22(2): 569.
31.	Shinoda K, Hirahara K, Iinuma T, et al. Thy1⁺IL-7⁺ lymphatic endothelial cells in iBALT provide a survival niche for memory T-helper cells in allergic airway inflammation. Proc Natl Acad Sci U S A, 2016, 113(20): E2842-E2851.
32.	Du X, Liu ZY, Tao XX, et al. Research progress on the pathogenesis of knee osteoarthritis. Orthop Surg, 2023, 15(9): 2213-2224.
33.	Zhang C, Lin Y, Yan CH, et al. Adipokine signaling pathways in osteoarthritis. Front Bioeng Biotechnol, 2022, 10: 865370.
34.	Cooper AJ, Gupta SR, Moustafa AF, et al. Sex/gender differences in obesity prevalence, comorbidities, and treatment. Curr Obes Rep, 2021, 10(4): 458-466.
35.	Palmer BF, Clegg DJ. The sexual dimorphism of obesity. Mol Cell Endocrinol, 2015, 402: 113-119.
36.	Oliveira MC, Vullings J, van de Loo FAJ. Osteoporosis and osteoarthritis are two sides of the same coin paid for obesity. Nutrition, 2020, 70: 110486.
37.	Eime R, Charity M, Harvey J, et al. Five-year changes in community-level sport participation, and the role of gender strategies. Front Sports Act Living, 2021, 3: 710666.
38.	Zeng CY, Zhang ZR, Tang ZM, et al. Benefits and mechanisms of exercise training for knee osteoarthritis. Front Physiol, 2021, 12: 794062.
39.	Varongot-Reille C, Barrero-Santiago L, Cuenca-Martínez F, et al. Effectiveness of exercise on pain intensity and physical function in patients with knee and hip osteoarthritis: an umbrella and mapping review with meta-meta-analysis. Disabil Rehabil, 2023, 12: 1-15.
40.	Li R, Chen H, Feng J, et al. Effectiveness of traditional chinese exercise for symptoms of knee osteoarthritis: a systematic review and meta-analysis of randomized controlled trials. Int J Environ Res Public Health, 2020, 17(21): 7873.
41.	Castrogiovanni P, Di Rosa M, Ravalli S, et al. Moderate physical activity as a prevention method for knee osteoarthritis and the role of synoviocytes as biological key. Int J Mol Sci, 2019, 20(3): 511.
42.	Nelligan RK, Hinman RS, Kasza J, et al. Effects of a self-directed web-based strengthening exercise and physical activity program supported by automated text messages for people with knee osteoarthritis: a randomized clinical trial. JAMA Intern Med, 2021, 181(6): 776-785.
43.	Kroshus E, Utter AC, Pierpoint LA, et al. The first decade of web-based sports injury surveillance: descriptive epidemiology of injuries in US high school boys’ wrestling (2005-2006 through 2013-2014) and National Collegiate Athletic Association men’s wrestling (2004-2005 through 2013-2014). J Athl Train, 2018, 53(12): 1143-1155.
44.	Bassett AJ, Ahlmen A, Rosendorf JM, et al. The biology of sex and sport. JBJS Rev, 2020, 8(3): e0140.
45.	Nuzzo JL. Sex differences in skeletal muscle fiber types: a meta-analysis. Clin Anat, 2024, 37(1): 81-91.
46.	Øiestad BE, Juhl CB, Culvenor AG, et al. Knee extensor muscle weakness is a risk factor for the development of knee osteoarthritis: an updated systematic review and meta-analysis including 46 819 men and women. Br J Sports Med, 2022, 56(6): 349-355.

1. Katz JN, Arant KR, Loeser RF. Diagnosis and treatment of hip and knee osteoarthritis: a review. JAMA, 2021, 325(6): 568-578.
2. Sharma L. Osteoarthritis of the knee. N Engl J Med, 2021, 384(1): 51-59.
3. Cui A, Li H, Wang D, et al. Global, regional prevalence, incidence and risk factors of knee osteoarthritis in population-based studies. EClinicalMedicine, 2020(29/30): 100587.
4. Srikanth VK, Fryer JL, Zhai G, et al. A meta-analysis of sex differences prevalence, incidence and severity of osteoarthritis. Osteoarthritis Cartilage, 2005, 13(9): 769-781.
5. Szilagyi IA, Waarsing JH, van Meurs JBJ, et al. A systematic review of the sex differences in risk factors for knee osteoarthritis. Rheumatology (Oxford), 2023, 62(6): 2037-2047.
6. Dong Y, Yan Y, Zhou J, et al. Evidence on risk factors for knee osteoarthritis in middle-older aged: a systematic review and meta analysis. J Orthop Surg Res, 2023, 18(1): 634.
7. Szilagyi IA, Waarsing JH, Schiphof D, et al. Towards sex-specific osteoarthritis risk models: evaluation of risk factors for knee osteoarthritis in males and females. Rheumatology (Oxford), 2022, 61(2): 648-657.
8. Hanna FS, Teichtahl AJ, Wluka AE, et al. Women have increased rates of cartilage loss and progression of cartilage defects at the knee than men: a gender study of adults without clinical knee osteoarthritis. Menopause, 2009, 16(4): 666-670.
9. Li D, Li S, Chen Q, et al. The prevalence of symptomatic knee osteoarthritis in relation to age, sex, area, region, and body mass index in China: a systematic review and meta-analysis. Front Med (Lausanne), 2020, 7: 304.
10. Pang H, Chen S, Klyne DM, et al. Low back pain and osteoarthritis pain: a perspective of estrogen. Bone Res, 2023, 11(1): 42.
11. Emmanuelle NE, Marie-Cécile V, Florence T, et al. Critical role of estrogens on bone homeostasis in both male and female: from physiology to medical implications. Int J Mol Sci, 2021, 22(4): 1568.
12. 牟利民, 张文豪, 张思平, 等. 绝经后女性退变性膝骨关节炎疼痛与性激素水平及关节液炎性因子的相关性研究. 中国全科医学, 2022, 25(29): 3652-3657.
13. Gilmer G, Bean AC, Iijima H, et al. Uncovering the “riddle of femininity” in osteoarthritis: a systematic review and meta-analysis of menopausal animal models and mathematical modeling of estrogen treatment. Osteoarthritis Cartilage, 2023, 31(4): 447-457.
14. Hanna FS, Wluka AE, Bell RJ, et al. Osteoarthritis and the postmenopausal woman: epidemiological, magnetic resonance imaging, and radiological findings. Semin Arthritis Rheum, 2004, 34(3): 631-636.
15. Lou C, Xiang G, Weng Q, et al. Menopause is associated with articular cartilage degeneration: a clinical study of knee joint in 860 women. Menopause, 2016, 23(11): 1239-1246.
16. Xu X, Li X, Liang Y, et al. Estrogen modulates cartilage and subchondral bone remodeling in an ovariectomized rat model of postmenopausal osteoarthritis. Med Sci Monit, 2019, 25: 3146-3153.
17. Jung JH, Bang CH, Song GG, et al. Knee osteoarthritis and menopausal hormone therapy in postmenopausal women: a nationwide cross-sectional study. Menopause, 2018, 26(6): 598-602.
18. Liu Y, Zhang M, Kong D, et al. High follicle-stimulating hormone levels accelerate cartilage damage of knee osteoarthritis in postmenopausal women through the PI3K/AKT/NF-κB pathway. FEBS Open Bio, 2020, 10(10): 2235-2245.
19. 刘亚平. 卵泡剌激素对绝经后女性膝骨关节炎软骨损伤的影响及机制研究. 济南: 山东大学, 2020.
20. Sasaki E, Chiba D, Ota S, et al. Reduced serum levels of anti-Mullerian hormone is a putative biomarker of early knee osteoarthritis in middle-aged females at menopausal transition. Sci Rep, 2021, 11(1): 4931.
21. Rowe E, Beauchamp MK, Astephen Wilson J. Age and sex differences in normative gait patterns. Gait Posture, 2021, 88: 109-115.
22. Phatama KY, Isma S, Devi LK, et al. Relationship of anterior knee pain with quadriceps angle and anthropometric measurements in an asian female population. Malays Orthop J, 2022, 16(2): 95-101.
23. Sharma R, Vaibhav V, Meshram R, et al. A systematic review on quadriceps angle in relation to knee abnormalities. Cureus, 2023, 15(1): e34355.
24. Kerrigan DC, Todd MK, Della Croce U. Gender differences in joint biomechanics during walking: normative study in young adults. Am J Phys Med Rehabil, 1998, 77(1): 2-7.
25. Lu Y, Zheng ZL, Lv J, et al. Relationships between morphological changes of lower limbs and gender during medial compartment knee osteoarthritis. Orthop Surg, 2019, 11(5): 835-844.
26. Ro DH, Lee DY, Moon G, et al. Sex differences in knee joint loading: cross-sectional study in geriatric population. J Orthop Res, 2017, 35(6): 1283-1289.
27. Zhang Y, Yang Y, Wang C, et al. Identification of diagnostic biomarkers of osteoarthritis based on multi-chip integrated analysis and machine learning. DNA Cell Biol, 2020: 16.
28. Zhong J, Xiang D, Ma X. Prediction and analysis of osteoarthritis hub genes with bioinformatics. Ann Transl Med, 2023, 11(2): 66.
29. Hame SL, Alexander RA. Knee osteoarthritis in women. Curr Rev Musculoskelet Med, 2013, 6(2): 182-187.
30. Li C, Zheng Z. Cartilage targets of knee osteoarthritis shared by both genders. Int J Mol Sci, 2021, 22(2): 569.
31. Shinoda K, Hirahara K, Iinuma T, et al. Thy1⁺IL-7⁺ lymphatic endothelial cells in iBALT provide a survival niche for memory T-helper cells in allergic airway inflammation. Proc Natl Acad Sci U S A, 2016, 113(20): E2842-E2851.
32. Du X, Liu ZY, Tao XX, et al. Research progress on the pathogenesis of knee osteoarthritis. Orthop Surg, 2023, 15(9): 2213-2224.
33. Zhang C, Lin Y, Yan CH, et al. Adipokine signaling pathways in osteoarthritis. Front Bioeng Biotechnol, 2022, 10: 865370.
34. Cooper AJ, Gupta SR, Moustafa AF, et al. Sex/gender differences in obesity prevalence, comorbidities, and treatment. Curr Obes Rep, 2021, 10(4): 458-466.
35. Palmer BF, Clegg DJ. The sexual dimorphism of obesity. Mol Cell Endocrinol, 2015, 402: 113-119.
36. Oliveira MC, Vullings J, van de Loo FAJ. Osteoporosis and osteoarthritis are two sides of the same coin paid for obesity. Nutrition, 2020, 70: 110486.
37. Eime R, Charity M, Harvey J, et al. Five-year changes in community-level sport participation, and the role of gender strategies. Front Sports Act Living, 2021, 3: 710666.
38. Zeng CY, Zhang ZR, Tang ZM, et al. Benefits and mechanisms of exercise training for knee osteoarthritis. Front Physiol, 2021, 12: 794062.
39. Varongot-Reille C, Barrero-Santiago L, Cuenca-Martínez F, et al. Effectiveness of exercise on pain intensity and physical function in patients with knee and hip osteoarthritis: an umbrella and mapping review with meta-meta-analysis. Disabil Rehabil, 2023, 12: 1-15.
40. Li R, Chen H, Feng J, et al. Effectiveness of traditional chinese exercise for symptoms of knee osteoarthritis: a systematic review and meta-analysis of randomized controlled trials. Int J Environ Res Public Health, 2020, 17(21): 7873.
41. Castrogiovanni P, Di Rosa M, Ravalli S, et al. Moderate physical activity as a prevention method for knee osteoarthritis and the role of synoviocytes as biological key. Int J Mol Sci, 2019, 20(3): 511.
42. Nelligan RK, Hinman RS, Kasza J, et al. Effects of a self-directed web-based strengthening exercise and physical activity program supported by automated text messages for people with knee osteoarthritis: a randomized clinical trial. JAMA Intern Med, 2021, 181(6): 776-785.
43. Kroshus E, Utter AC, Pierpoint LA, et al. The first decade of web-based sports injury surveillance: descriptive epidemiology of injuries in US high school boys’ wrestling (2005-2006 through 2013-2014) and National Collegiate Athletic Association men’s wrestling (2004-2005 through 2013-2014). J Athl Train, 2018, 53(12): 1143-1155.
44. Bassett AJ, Ahlmen A, Rosendorf JM, et al. The biology of sex and sport. JBJS Rev, 2020, 8(3): e0140.
45. Nuzzo JL. Sex differences in skeletal muscle fiber types: a meta-analysis. Clin Anat, 2024, 37(1): 81-91.
46. Øiestad BE, Juhl CB, Culvenor AG, et al. Knee extensor muscle weakness is a risk factor for the development of knee osteoarthritis: an updated systematic review and meta-analysis including 46 819 men and women. Br J Sports Med, 2022, 56(6): 349-355.

West China Medical Journal

Research progress on the correlation between gender differences and the incidence of knee osteoarthritis

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