Exploration of Endocrine and Metabolic Diseases

Table 1. Sex-specific differences in OA by joint: epidemiology and contributing factors in women.

Joint	Prevalence in women vs. men	Female-specific factors	Key references
Hand OA	Higher in women, especially after age 50, incidence increases markedly after menopause	Menopause-related estrogen decline, higher frequency of inflammatory/erosive phenotypes, polyarticular involvement	[4, 10–13, 16, 17]
Knee OA	Higher in women, particularly after menopause	Obesity, altered biomechanics (alignment, muscle strength), greater symptom severity, and progression	[4, 10, 12, 13, 15, 16]
Hip OA	Similar or slightly higher in men (population-dependent), more strongly associated with structural and morphological factors	Differences in hip morphology and a less clear hormonal influence	[13, 16, 17]
Spine OA	Mixed distribution	Postmenopausal degenerative changes, interaction of hormonal factors with mechanical load, and sex-specific degeneration patterns	[10, 13, 19–21]

Return to article view

OA: osteoarthritis.

Declarations

Author contributions

MV: Conceptualization, Writing—original draft, Writing—review & editing. NEL: Conceptualization, Writing—original draft, Writing—review & editing. Both authors read and approved the submitted version.

Conflicts of interest

The authors declare that there are no conflicts of interest.

Ethical approval

Not applicable.

Consent to participate

Not applicable.

Consent to publication

Not applicable.

Availability of data and materials

Not applicable.

Funding

Not applicable.

Copyright

Publisher’s note

Open Exploration maintains a neutral stance on jurisdictional claims in published institutional affiliations and maps. All opinions expressed in this article are the personal views of the author(s) and do not represent the stance of the editorial team or the publisher.

References

Courties A, Kouki I, Soliman N, Mathieu S, Sellam J. Osteoarthritis year in review 2024: Epidemiology and therapy. Osteoarthritis Cartilage. 2024;32:1397–404. [DOI] [PubMed]

Hayashi D, Roemer FW, Link T, Li X, Kogan F, Segal NA, et al. Latest advancements in imaging techniques in OA. Ther Adv Musculoskelet Dis. 2022;14:1759720X221146621. [DOI] [PubMed] [PMC]

Cross M, Smith E, Hoy D, Nolte S, Ackerman I, Fransen M, et al. The global burden of hip and knee osteoarthritis: estimates from the global burden of disease 2010 study. Ann Rheum Dis. 2014;73:1323–30. [DOI] [PubMed]

Srikanth VK, Fryer JL, Zhai G, Winzenberg TM, Hosmer D, Jones G. A meta-analysis of sex differences prevalence, incidence and severity of osteoarthritis. Osteoarthritis Cartilage. 2005;13:769–81. [DOI] [PubMed]

Sniekers YH, Weinans H, van Osch GJ, van Leeuwen JP. Oestrogen is important for maintenance of cartilage and subchondral bone in a murine model of knee osteoarthritis. Arthritis Res Ther. 2010;12:R182. [DOI] [PubMed] [PMC]

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;5:e508–22. [DOI] [PubMed] [PMC]

He Y, Jiang W, Wang W. Global burden of osteoarthritis in adults aged 30 to 44 years, 1990 to 2019: results from the Global Burden of Disease Study 2019. BMC Musculoskelet Disord. 2024;25:303. [DOI] [PubMed] [PMC]

Hunter DJ, Bierma-Zeinstra S. Osteoarthritis. Lancet. 2019;393:1745–59. [DOI] [PubMed]

Mendy A, Park J, Vieira ER. Osteoarthritis and risk of mortality in the USA: a population-based cohort study. Int J Epidemiol. 2018;47:1821–9. [DOI] [PubMed] [PMC]

10.

Vina ER, Kwoh CK. Epidemiology of osteoarthritis: literature update. Curr Opin Rheumatol. 2018;30:160–7. [DOI] [PubMed] [PMC]

11.

Segal NA, Nilges JM, Oo WM. Sex differences in osteoarthritis prevalence, pain perception, physical function and therapeutics. Osteoarthritis Cartilage. 2024;32:1045–53. [DOI] [PubMed]

12.

Dennison EM. Osteoarthritis: The importance of hormonal status in midlife women. Maturitas. 2022;165:8–11. [DOI] [PubMed]

13.

Zhang Y, Jordan JM. Epidemiology of osteoarthritis. Clin Geriatr Med. 2010;26:355–69. [DOI] [PubMed] [PMC]

14.

Deshpande BR, Katz JN, Solomon DH, Yelin EH, Hunter DJ, Messier SP, et al. Number of Persons With Symptomatic Knee Osteoarthritis in the US: Impact of Race and Ethnicity, Age, Sex, and Obesity. Arthritis Care Res (Hoboken). 2016;68:1743–50. [DOI] [PubMed] [PMC]

15.

Cui A, Li H, Wang D, Zhong J, Chen Y, Lu H. Global, regional prevalence, incidence and risk factors of knee osteoarthritis in population-based studies. EClinicalMedicine. 2020;29–30:100587. [DOI] [PubMed] [PMC]

16.

Prieto-Alhambra D, Judge A, Javaid MK, Cooper C, Diez-Perez A, Arden NK. Incidence and risk factors for clinically diagnosed knee, hip and hand osteoarthritis: influences of age, gender and osteoarthritis affecting other joints. Ann Rheum Dis. 2014;73:1659–64. [DOI] [PubMed] [PMC]

17.

Corti MC, Rigon C. Epidemiology of osteoarthritis: prevalence, risk factors and functional impact. Aging Clin Exp Res. 2003;15:359–63. [DOI] [PubMed]

18.

Sophia Fox AJ, Bedi A, Rodeo SA. The basic science of articular cartilage: structure, composition, and function. Sports Health. 2009;1:461–8. [DOI] [PubMed] [PMC]

19.

Lv Y, Tian W, Chen D, Liu Y, Wang L, Duan F. The prevalence and associated factors of symptomatic cervical Spondylosis in Chinese adults: a community-based cross-sectional study. BMC Musculoskelet Disord. 2018;19:325. [DOI] [PubMed] [PMC]

20.

Shelby T, Mills ES, Ton A, Wang JC, Hah RJ, Qureshi SA, et al. The Role of Sex Hormones in Degenerative Disc Disease. Global Spine J. 2023;13:2096–9. [DOI] [PubMed] [PMC]

21.

Jarraya M, Guermazi A, Lorbergs AL, Brochin E, Kiel DP, Bouxsein ML, et al. A longitudinal study of disc height narrowing and facet joint osteoarthritis at the thoracic and lumbar spine, evaluated by computed tomography: the Framingham Study. Spine J. 2018;18:2065–73. [DOI] [PubMed] [PMC]

22.

Lories RJ, Luyten FP. Overview of joint and cartilage biology. In: Thakker RV, Whyte MP, Eisman JA, Igarashi T, editors. 2nd ed. London: Academic Press; 2018. pp. 209–25. [DOI]

23.

Zhai G. Alteration of Metabolic Pathways in Osteoarthritis. Metabolites. 2019;9:11. [DOI] [PubMed] [PMC]

24.

Wei P, Bao R. Intra-Articular Mesenchymal Stem Cell Injection for Knee Osteoarthritis: Mechanisms and Clinical Evidence. Int J Mol Sci. 2022;24:59. [DOI] [PubMed] [PMC]

25.

Şenol MS, Özer H. Comparative Kinesiology of the Human Body. In: Angin S, Ilçin NE, editors. Architecture of cartilage tissue and its adaptation to pathological conditions. London: Academic Press; 2020. pp. 91–100. [DOI]

26.

McCarty WJ, Nguyen QT, Hui AY, Chen AC, Sah RL. Comprehensive Biomaterials. In: Ducheyne P, editor. Cartilage tissue engineering. Amsterdam: Elsevier; 2011. pp. 199–212. [DOI]

27.

Wilson W, Driessen NJ, van Donkelaar CC, Ito K. Prediction of collagen orientation in articular cartilage by a collagen remodeling algorithm. Osteoarthritis Cartilage. 2006;14:1196–202. [DOI] [PubMed]

28.

Gao Y, Liu S, Huang J, Guo W, Chen J, Zhang L, et al. The ECM-cell interaction of cartilage extracellular matrix on chondrocytes. Biomed Res Int. 2014;2014:648459. [DOI] [PubMed] [PMC]

29.

Eyre DR. The collagens of articular cartilage. Semin Arthritis Rheum. 1991;21:2–11. [DOI] [PubMed]

30.

Ouyang Z, Dong L, Yao F, Wang K, Chen Y, Li S, et al. Cartilage-Related Collagens in Osteoarthritis and Rheumatoid Arthritis: From Pathogenesis to Therapeutics. Int J Mol Sci. 2023;24:9841. [DOI] [PubMed] [PMC]

31.

Di Martino A, Barile F, D’Agostino C, Castafaro V, Cerasoli T, Mora P, et al. Are there gender-specific differences in hip and knee cartilage composition and degeneration? Eur J Orthop Surg Traumatol. 2024;34:1901–10. [DOI] [PubMed] [PMC]

32.

Kumar D, Souza RB, Subburaj K, MacLeod TD, Singh J, Calixto NE, et al. Are There Sex Differences in Knee Cartilage Composition and Walking Mechanics in Healthy and Osteoarthritis Populations? Clin Orthop Relat Res. 2015;473:2548–58. [DOI] [PubMed] [PMC]

33.

Ariyachaikul S, Sriburee S, Thonglorm N, Kanthain R, Jankaew A. Comparison of knee articular cartilage thickness across sex and age groups in healthy adults. J Exp Orthop. 2025;12:e70490. [DOI] [PubMed] [PMC]

34.

Eckstein F, Wirth W, Putz R. Sexual dimorphism in articular tissue anatomy - Key to understanding sex differences in osteoarthritis? Osteoarthritis Cartilage. 2024;32:1019–31. [DOI] [PubMed]

35.

Abdelnasser MK, Abdelhameed MA, Bassem M, Adam MF, Bakr HM, Khalifa YE. Sexual dimorphism of the posterior condylar offset of the femur and the medial posterior slope of the tibia in non-arthritic knees of Egyptian adults: an MRI study. J Orthop Surg Res. 2023;18:353. [DOI] [PubMed] [PMC]

36.

Palazzo C, Nguyen C, Lefevre-Colau MM, Rannou F, Poiraudeau S. Risk factors and burden of osteoarthritis. Ann Phys Rehabil Med. 2016;59:134–8. [DOI] [PubMed]

37.

Dubois L, Ohm Kyvik K, Girard M, Tatone-Tokuda F, Pérusse D, Hjelmborg J, et al. Genetic and environmental contributions to weight, height, and BMI from birth to 19 years of age: an international study of over 12,000 twin pairs. PLoS One. 2012;7:e30153. [DOI] [PubMed] [PMC]

38.

He Y, Li Z, Alexander PG, Ocasio-Nieves BD, Yocum L, Lin H, et al. Pathogenesis of Osteoarthritis: Risk Factors, Regulatory Pathways in Chondrocytes, and Experimental Models. Biology (Basel). 2020;9:194. [DOI] [PubMed] [PMC]

39.

Spector TD, Cicuttini F, Baker J, Loughlin J, Hart D. Genetic influences on osteoarthritis in women: a twin study. BMJ. 1996;312:940–3. [DOI] [PubMed] [PMC]

40.

Zhai G, Huang J. Genetics of osteoarthritis. Best Pract Res Clin Rheumatol. 2024;38:101972. [DOI] [PubMed]

41.

Sandell LJ. Etiology of osteoarthritis: genetics and synovial joint development. Nat Rev Rheumatol. 2012;8:77–89. [DOI] [PubMed]

42.

Warner SC, Valdes AM. The Genetics of Osteoarthritis: A Review. J Funct Morphol Kinesiol. 2016;1:140–53. [DOI]

43.

Aubourg G, Rice SJ, Bruce-Wootton P, Loughlin J. Genetics of osteoarthritis. Osteoarthritis Cartilage. 2022;30:636–49. [DOI] [PubMed] [PMC]

44.

Barter MJ, Gomez R, Hyatt S, Cheung K, Skelton AJ, Xu Y, et al. The long non-coding RNA ROCR contributes to SOX9 expression and chondrogenic differentiation of human mesenchymal stem cells. Development. 2017;144:4510–21. [DOI] [PubMed] [PMC]

45.

Boer CG. Osteoarthritis year in review 2024: Genetics, genomics, and epigenetics. Osteoarthritis Cartilage. 2025;33:50–7. [DOI] [PubMed]

46.

Magnusson K, Turkiewicz A, Rydén M, Englund M. Genetic Influence on Osteoarthritis Versus Other Rheumatic Diseases. Arthritis Rheumatol. 2024;76:206–15. [DOI] [PubMed]

47.

Anker-Hansen C, Pirouzifard M, Sundquist J, Sundquist K, Zöller B. Familial risks of five types of osteoarthritis in first-, second- and third-degree relatives—A nationwide Swedish family study. Osteoarthr Cartil Open. 2025;7:100637. [DOI] [PubMed] [PMC]

48.

Weldingh E, Johnsen MB, Hagen KB, Østerås N, Risberg MA, Natvig B, et al. The Maternal and Paternal Effects on Clinically and Surgically Defined Osteoarthritis. Arthritis Rheumatol. 2019;71:1844–8. [DOI] [PubMed]

49.

Overstreet DS, Strath LJ, Jordan M, Jordan IA, Hobson JM, Owens MA, et al. A Brief Overview: Sex Differences in Prevalent Chronic Musculoskeletal Conditions. Int J Environ Res Public Health. 2023;20:4521. [DOI] [PubMed] [PMC]

50.

Szilagyi IA, Waarsing JH, van Meurs JBJ, Bierma-Zeinstra SMA, Schiphof D. A systematic review of the sex differences in risk factors for knee osteoarthritis. Rheumatology (Oxford). 2023;62:2037–47. [DOI] [PubMed] [PMC]

51.

Elboim-Gabyzon M, Rozen N, Laufer Y. Gender differences in pain perception and functional ability in subjects with knee osteoarthritis. ISRN Orthop. 2012;2012:413105. [DOI] [PubMed] [PMC]

52.

Elzeblawy Hassan, H. Effect of elderly women’s socio-demographic characteristics on knee osteoarthritis pain. Am J Med Sci Med. 2023;11:39–46. [DOI]

53.

Keefe FJ, Lefebvre JC, Egert JR, Affleck G, Sullivan MJ, Caldwell DS. The relationship of gender to pain, pain behavior, and disability in osteoarthritis patients: the role of catastrophizing. Pain. 2000;87:325–34. [DOI] [PubMed]

54.

Quartana PJ, Campbell CM, Edwards RR. Pain catastrophizing: a critical review. Expert Rev Neurother. 2009;9:745–58. [DOI] [PubMed] [PMC]

55.

Bartley EJ, Fillingim RB. Sex differences in pain: a brief review of clinical and experimental findings. Br J Anaesth. 2013;111:52–8. [DOI] [PubMed] [PMC]

56.

Failla MD, Beach PA, Atalla S, Dietrich MS, Bruehl S, Cowan RL, et al. Gender Differences in Pain Threshold, Unpleasantness, and Descending Pain Modulatory Activation Across the Adult Life Span: A Cross Sectional Study. J Pain. 2024;25:1059–69. [DOI] [PubMed] [PMC]

57.

Paranjape S, Singhania N. Effect of body positions on quadriceps angle measurement. SciMed J. 2019;1:20–4. [DOI]

58.

Carreiro JE. An Osteopathic Approach to Children. In: Carreiro JE, editor. The musculoskeletal system. 2nd ed. Edinburgh: Churchill Livingstone; 2009. pp. 15–52. [DOI]

59.

Walter KL. Anterior Cruciate Ligament Injuries in Female Athletes. JAMA. 2025;333:1648. [DOI] [PubMed]

60.

Gong Z, Li J, He Z, Li S, Cao P, Ruan G, et al. Quadriceps strength is negatively associated with knee joint structural abnormalities-data from osteoarthritis initiative. BMC Musculoskelet Disord. 2022;23:784. [DOI] [PubMed] [PMC]

61.

Shen P, Chen X, Wu Y, Yang QJ, Yu SJ, Wang XQ. Analysis of Quadriceps Strength and Knee Pain. Arch Phys Med Rehabil. 2024;105:1900–7. [DOI] [PubMed]

62.

Haghighi M, Miri H, Pakarha S. Comparison of the effect of quadriceps strengthening exercises and combined exercises on pain, balance, quality of life, and relative strength of women aged 50–60 years with knee osteoarthritis: a controlled trial. J Res Sport Rehabil. 2025;13. [DOI]

63.

Nadimi R, Haidary M. The effect of resistance training and quadriceps strengthening exercises on pain, walking speed, quality of life, and balance in elderly women with knee osteoarthritis. J Orthop Geriatr Exerc. 2025;10:67–80. [DOI]

64.

Ezra D, Masharawi Y, Salame K, Slon V, Alperovitch-Najenson D, Hershkovitz I. Demographic aspects in cervical vertebral bodies’ size and shape (C3–C7): a skeletal study. Spine J. 2017;17:135–42. [DOI] [PubMed]

65.

Asai T, Sakuma E, Mizutani T, Ishizaka Y, Ori K, Ueki T. Sex- and Age-related Differences in Spinal Degeneration: An Anatomical and Magnetic Resonance Imaging Study of the Human Spine. Prog Rehabil Med. 2022;7:20220011. [DOI] [PubMed] [PMC]

66.

Carmo GP, Grigioni J, Fernandes FAO, Alves de Sousa RJ. Biomechanics of Traumatic Head and Neck Injuries on Women: A State-of-the-Art Review and Future Directions. Biology (Basel). 2023;12:83. [DOI] [PubMed] [PMC]

67.

Stemper BD, Derosia JJ, Yogananan N, Pintar FA, Shender BS, Paskoff GR. Gender dependent cervical spine anatomical differences in size-matched volunteers—biomed 2009. Biomed Sci Instrum. 2009;45:149–54. [PubMed]

68.

Petrie KA, Burbank K, Sizer PS, James CR, Zumwalt M. The Active Female. In: Robert-McComb JJ, Zumwalt M, Fernandez-del-Valle M, editors. Considerations of sex differences in musculoskeletal anatomy between males and females. Cham: Springer; 2023. pp. 3–24. [DOI]

69.

Bagwell K, Williams FLE. Degenerative joint changes of the thoracic spine with respect to sex and age. Rev Argent Antropol Biol. 2022;24. [DOI]

70.

Calleja-Agius J, Muscat-Baron Y, Brincat MP. Estrogens and the intervertebral disc. Menopause Int. 2009;15:127–30. [DOI] [PubMed]

71.

Wang YXJ. Menopause as a potential cause for higher prevalence of low back pain in women than in age-matched men. J Orthop Translat. 2016;8:1–4. [DOI] [PubMed] [PMC]

72.

Gambacciani M, Pepe A, Cappagli B, Palmieri E, Genazzani AR. The relative contributions of menopause and aging to postmenopausal reduction in intervertebral disk height. Climacteric. 2007;10:298–305. [DOI] [PubMed]

73.

Hay O, Dar G, Abbas J, Stein D, May H, Masharawi Y, et al. The Lumbar Lordosis in Males and Females, Revisited. PLoS One. 2015;10:e0133685. [DOI] [PubMed] [PMC]

74.

Gilsanz V, Boechat MI, Gilsanz R, Loro ML, Roe TF, Goodman WG. Gender differences in vertebral sizes in adults: biomechanical implications. Radiology. 1994;190:678–82. [DOI] [PubMed]

75.

Tian W, Lv Y, Liu Y, Xiao B, Han X. The high prevalence of symptomatic degenerative lumbar osteoarthritis in Chinese adults: a population-based study. Spine (Phila Pa 1976). 2014;39:1301–10. [DOI] [PubMed] [PMC]

76.

Hawellek T, Meier MP, Seitz MT, Uhlig J, Hosseini ASA, Beil FT, et al. Morphological Parameters of the Hip Joint and Its Relation to Gender, Joint Side and Age-A CT-Based Study. Diagnostics (Basel). 2022;12:1774. [DOI] [PubMed] [PMC]

77.

Maillefert JF, Gueguen A, Monreal M, Nguyen M, Berdah L, Lequesne M, et al. Sex differences in hip osteoarthritis: results of a longitudinal study in 508 patients. Ann Rheum Dis. 2003;62:931–4. [DOI] [PubMed] [PMC]

78.

Solarino G, Vicenti G, Picca G, Rifino F, Carrozzo M, Moretti B. A review of gender differences in hip fracture anatomy, morbidity, mortality and function. Ital J Gender-Specific Med. 2016;2:55–9. [DOI]

79.

Nakahara I, Takao M, Sakai T, Nishii T, Yoshikawa H, Sugano N. Gender differences in 3D morphology and bony impingement of human hips. J Orthop Res. 2011;29:333–9. [DOI] [PubMed]

80.

Abd-Eltawab AE, Ameer MA, Eladl MA, El-Sherbiny M, Ebrahim HA, Elsherbini DMA. Sexual Dimorphism Impact on the Ground Reaction Force Acting on the Mediolateral Direction During Level Walking: Hip Abductor Muscle Biomechanics and Its Correlation to GRF Moment Arm. Front Bioeng Biotechnol. 2022;10:863194. [DOI] [PubMed] [PMC]

81.

Hussain SM, Cicuttini FM, Alyousef B, Wang Y. Female hormonal factors and osteoarthritis of the knee, hip and hand: a narrative review. Climacteric. 2018;21:132–9. [DOI] [PubMed]

82.

Aloisi AM, Bonifazi M. Sex hormones, central nervous system and pain. Horm Behav. 2006;50:1–7. [DOI] [PubMed]

83.

Pang H, Chen S, Klyne DM, Harrich D, Ding W, Yang S, et al. Low back pain and osteoarthritis pain: a perspective of estrogen. Bone Res. 2023;11:42. [DOI] [PubMed] [PMC]

84.

Mahajan A, Patni R, Verma S. Low Back Pain and Menopause. J Midlife Health. 2019;10:163–4. [DOI] [PubMed] [PMC]

85.

Kozinoga M, Majchrzycki M, Piotrowska S. Low back pain in women before and after menopause. Prz Menopauzalny. 2015;14:203–7. [DOI] [PubMed] [PMC]

86.

Xu H, Xiao W, Ding C, Zou J, Zhou D, Wang J, et al. Global burden of osteoarthritis among postmenopausal women in 204 countries and territories: a systematic analysis for the Global Burden of Disease Study 2021. BMJ Glob Health. 2025;10:e017198. [DOI] [PubMed] [PMC]

87.

Linn S, Murtaugh B, Casey E. Role of sex hormones in the development of osteoarthritis. PM R. 2012;4:S169–73. [DOI] [PubMed]

88.

Roman-Blas JA, Castañeda S, Largo R, Herrero-Beaumont G. Osteoarthritis associated with estrogen deficiency. Arthritis Res Ther. 2009;11:241. [DOI] [PubMed] [PMC]

89.

Athnaiel O, Davidson N, Mangat J, Nasr NF, Knezevic NN. Gonadal Hormone Changes with Aging and Their Impact on Chronic Pain. Cells. 2025;14:123. [DOI] [PubMed] [PMC]

90.

Bay-Jensen AC, Slagboom E, Chen-An P, Alexandersen P, Qvist P, Christiansen C, et al. Role of hormones in cartilage and joint metabolism: understanding an unhealthy metabolic phenotype in osteoarthritis. Menopause. 2013;20:578–86. [DOI] [PubMed]

91.

Martín-Millán M, Castañeda S. Estrogens, osteoarthritis and inflammation. Joint Bone Spine. 2013;80:368–73. [DOI] [PubMed]

92.

Sowers MR, McConnell D, Jannausch M, Buyuktur AG, Hochberg M, Jamadar DA. Estradiol and its metabolites and their association with knee osteoarthritis. Arthritis Rheum. 2006;54:2481–7. [DOI] [PubMed]

93.

Ravn P, Warming L, Christgau S, Christiansen C. The effect on cartilage of different forms of application of postmenopausal estrogen therapy: comparison of oral and transdermal therapy. Bone. 2004;35:1216–21. [DOI]

94.

Kapila S, Wang W, Uston K. Matrix metalloproteinase induction by relaxin causes cartilage matrix degradation in target synovial joints. Ann N Y Acad Sci. 2009;1160:322–8. [DOI] [PubMed] [PMC]

95.

Jin X, Wang BH, Wang X, Antony B, Zhu Z, Han W, et al. Associations between endogenous sex hormones and MRI structural changes in patients with symptomatic knee osteoarthritis. Osteoarthritis Cartilage. 2017;25:1100–6. [DOI] [PubMed]

96.

Kenny AM, Kleppinger A, Annis K, Rathier M, Browner B, Judge JO, et al. Effects of transdermal testosterone on bone and muscle in older men with low bioavailable testosterone levels, low bone mass, and physical frailty. J Am Geriatr Soc. 2010;58:1134–43. [DOI] [PubMed] [PMC]

97.

Freystaetter G, Fischer K, Orav EJ, Egli A, Theiler R, Münzer T, et al. Total Serum Testosterone and Western Ontario and McMaster Universities Osteoarthritis Index Pain and Function Among Older Men and Women With Severe Knee Osteoarthritis. Arthritis Care Res (Hoboken). 2020;72:1511–8. [DOI] [PubMed] [PMC]

98.

Ma N, Gao F. Correlation between low testosterone levels and the risk of osteoarthritis: a cross-sectional analysis of NHANES data (2011–2016). BMC Musculoskelet Disord. 2025;26:23. [DOI] [PubMed] [PMC]

99.

Cheng L, Wang S. Lower serum testosterone is associated with increased likelihood of arthritis. Sci Rep. 2023;13:19241. [DOI] [PubMed] [PMC]

100.

Schwanbeck SR, Cornish SM, Barss T, Chilibeck PD. Effects of Training With Free Weights Versus Machines on Muscle Mass, Strength, Free Testosterone, and Free Cortisol Levels. J Strength Cond Res. 2020;34:1851–9. [DOI] [PubMed]

101.

King LK, March L, Anandacoomarasamy A. Obesity & osteoarthritis. Indian J Med Res. 2013;138:185–93. [PubMed] [PMC]

102.

Nedunchezhiyan U, Varughese I, Sun AR, Wu X, Crawford R, Prasadam I. Obesity, Inflammation, and Immune System in Osteoarthritis. Front Immunol. 2022;13:907750. [DOI] [PubMed] [PMC]

103.

Sobieh BH, El-Mesallamy HO, Kassem DH. Beyond mechanical loading: The metabolic contribution of obesity in osteoarthritis unveils novel therapeutic targets. Heliyon. 2023;9:e15700. [DOI] [PubMed] [PMC]

104.

Jiang L, Tian W, Wang Y, Rong J, Bao C, Liu Y, et al. Body mass index and susceptibility to knee osteoarthritis: a systematic review and meta-analysis. Joint Bone Spine. 2012;79:291–7. [DOI] [PubMed]

105.

Coggon D, Reading I, Croft P, McLaren M, Barrett D, Cooper C. Knee osteoarthritis and obesity. Int J Obes Relat Metab Disord. 2001;25:622–7. [DOI] [PubMed]

106.

Grotle M, Hagen KB, Natvig B, Dahl FA, Kvien TK. Obesity and osteoarthritis in knee, hip and/or hand: an epidemiological study in the general population with 10 years follow-up. BMC Musculoskelet Disord. 2008;9:132. [DOI] [PubMed] [PMC]

107.

Stürmer T, Günther KP, Brenner H. Obesity, overweight and patterns of osteoarthritis: the Ulm Osteoarthritis Study. J Clin Epidemiol. 2000;53:307–13. [DOI] [PubMed]

108.

Duong V, Abdel Shaheed C, Ferreira ML, Narayan SW, Venkatesha V, Hunter DJ, et al. Risk factors for the development of knee osteoarthritis across the lifespan: A systematic review and meta-analysis. Osteoarthritis Cartilage. 2025;33:1162–79. [DOI] [PubMed]

109.

Ackerman IN, Osborne RH. Obesity and increased burden of hip and knee joint disease in Australia: results from a national survey. BMC Musculoskelet Disord. 2012;13:254. [DOI] [PubMed] [PMC]

110.

Lievense AM, Bierma-Zeinstra SM, Verhagen AP, van Baar ME, Verhaar JA, Koes BW. Influence of obesity on the development of osteoarthritis of the hip: a systematic review. Rheumatology (Oxford). 2002;41:1155–62. [DOI] [PubMed]

111.

Reyes C, Leyland KM, Peat G, Cooper C, Arden NK, Prieto-Alhambra D. Association Between Overweight and Obesity and Risk of Clinically Diagnosed Knee, Hip, and Hand Osteoarthritis: A Population-Based Cohort Study. Arthritis Rheumatol. 2016;68:1869–75. [DOI] [PubMed] [PMC]

112.

Jin X, Gibson AA, Gale J, Schneuer F, Ding D, March L, et al. Does weight loss reduce the incidence of total knee and hip replacement for osteoarthritis?—A prospective cohort study among middle-aged and older adults with overweight or obesity. Int J Obes (Lond). 2021;45:1696–704. [DOI] [PubMed] [PMC]

113.

Christensen R, Bartels EM, Astrup A, Bliddal H. Effect of weight reduction in obese patients diagnosed with knee osteoarthritis: a systematic review and meta-analysis. Ann Rheum Dis. 2007;66:433–9. [DOI] [PubMed] [PMC]

114.

Onggo JR, Onggo JD, de Steiger R, Hau R. Greater risks of complications, infections, and revisions in the obese versus non-obese total hip arthroplasty population of 2,190,824 patients: a meta-analysis and systematic review. Osteoarthritis Cartilage. 2020;28:31–44. [DOI] [PubMed]

115.

Collins AT, Hu G, Newman H, Reinsvold MH, Goldsmith MR, Twomey-Kozak JN, et al. Obesity alters the collagen organization and mechanical properties of murine cartilage. Sci Rep. 2021;11:1626. [DOI] [PubMed] [PMC]

116.

Sellam J, Rat AC, Fellahi S, Bastard JP, Ngueyon Sime W, Ea HK, et al. Pain in women with knee and/or hip osteoarthritis is related to systemic inflammation and to adipose tissue dysfunction: Cross-sectional results of the KHOALA cohort. Semin Arthritis Rheum. 2021;51:129–36. [DOI] [PubMed]

117.

Berenbaum F. Osteoarthritis as an inflammatory disease (osteoarthritis is not osteoarthrosis! Osteoarthritis Cartilage. 2013;21:16–21. [DOI] [PubMed]

118.

Heard BJ, Fritzler MJ, Wiley JP, McAllister J, Martin L, El-Gabalawy H, et al. Intraarticular and systemic inflammatory profiles may identify patients with osteoarthritis. J Rheumatol. 2013;40:1379–87. [DOI] [PubMed]

119.

Stürmer T, Brenner H, Koenig W, Günther KP. Severity and extent of osteoarthritis and low grade systemic inflammation as assessed by high sensitivity C reactive protein. Ann Rheum Dis. 2004;63:200–5. [DOI] [PubMed] [PMC]

120.

Perruccio AV, Chandran V, Power JD, Kapoor M, Mahomed NN, Gandhi R. Systemic inflammation and painful joint burden in osteoarthritis: a matter of sex? Osteoarthritis Cartilage. 2017;25:53–9. [DOI] [PubMed]

121.

Liu X, Zheng Y, Li H, Ma Y, Cao R, Zheng Z, et al. The role of metabolites in the progression of osteoarthritis: Mechanisms and advances in therapy. J Orthop Translat. 2025;50:56–70. [DOI] [PubMed] [PMC]

122.

Nemet M, Blazin T, Milutinovic S, Cebovic T, Stanojevic D, Zvekic Svorcan J. Association Between Metabolic Syndrome, Its Components, and Knee Osteoarthritis in Premenopausal and Menopausal Women: A Pilot Study. Cureus. 2022;14:e26726. [DOI] [PubMed] [PMC]

123.

Wang X, Hunter D, Xu J, Ding C. Metabolic triggered inflammation in osteoarthritis. Osteoarthritis Cartilage. 2015;23:22–30. [DOI] [PubMed]

124.

Zhuo Q, Yang W, Chen J, Wang Y. Metabolic syndrome meets osteoarthritis. Nat Rev Rheumatol. 2012;8:729–37. [DOI] [PubMed]

125.

Zhang S, Wang D, Zhao J, Zhao H, Xie P, Zheng L, et al. Metabolic syndrome increases osteoarthritis risk: findings from the UK Biobank prospective cohort study. BMC Public Health. 2024;24:233. [DOI] [PubMed] [PMC]

126.

Wilman MV, Lane NE. The importance of vitamin D. Rheumatol Orthop Med. 2020;5:1–9. [DOI]

127.

Timms PM, Mannan N, Hitman GA, Noonan K, Mills PG, Syndercombe-Court D, et al. Circulating MMP9, vitamin D and variation in the TIMP-1 response with VDR genotype: mechanisms for inflammatory damage in chronic disorders? QJM. 2002;95:787–96. [DOI] [PubMed]

128.

Yıldırım YA, Ozturk A, Doğruel F, Saraçoğlu H, Yazıcı C. Serum vitamin D concentration is inversely associated with matrix metalloproteinase-9 level in periodontal diseases. J Periodontol. 2025;96:663–74. [DOI] [PubMed] [PMC]

129.

Laslett LL, Quinn S, Burgess JR, Parameswaran V, Winzenberg TM, Jones G, et al. Moderate vitamin D deficiency is associated with changes in knee and hip pain in older adults: a 5-year longitudinal study. Ann Rheum Dis. 2014;73:697–703. [DOI] [PubMed]

130.

Vidal M, Lane NE. Vitamin D and Its Role in Rheumatic Diseases. Metabolites. 2025;15:259. [DOI] [PubMed] [PMC]

131.

Escobar-Morreale HF. Polycystic ovary syndrome: definition, aetiology, diagnosis and treatment. Nat Rev Endocrinol. 2018;14:270–284. [DOI] [PubMed]

132.

Stener-Victorin E, Teede H, Norman RJ, Legro R, Goodarzi MO, Dokras A, et al. Polycystic ovary syndrome. Nat Rev Dis Primers. 2024;10:27. [DOI] [PubMed]

133.

Joham AE, Norman RJ, Stener-Victorin E, Legro RS, Franks S, Moran LJ, et al. Polycystic ovary syndrome. Lancet Diabetes Endocrinol. 2022;10:668–80. [DOI] [PubMed]

134.

Kamal EE, Hamada HA, Ashour RS, Yousef AM, Elbesh RM. Biomechanical changes in females with poly cystic ovarian syndrome: a case-control study. Sci Rep. 2025;15:11190. [DOI] [PubMed] [PMC]

135.

Sharmeen S, Nomani H, Taub E, Carlson H, Yao Q. Polycystic ovary syndrome: epidemiologic assessment of prevalence of systemic rheumatic and autoimmune diseases. Clin Rheumatol. 2021;40:4837–43. [DOI] [PubMed]

136.

Kluzek S, Rubin KH, Sanchez-Santos M, O’Hanlon MS, Andersen M, Glintborg D, et al. Accelerated osteoarthritis in women with polycystic ovary syndrome: a prospective nationwide registry-based cohort study. Arthritis Res Ther. 2021;23:225. [DOI] [PubMed] [PMC]

137.

Deniz A, Kehribar L. The association between knee osteoarthritis and polycystic ovary syndrome in postmenopausal women: preliminary results. Eur Rev Med Pharmacol Sci. 2021;25:4895–9. [DOI] [PubMed]

138.

Kabakchieva P, Georgiev T, Gateva A, Hristova J, Kamenov Z. Polycystic ovary syndrome and (pre)osteoarthritis: assessing the link between hyperandrogenism in young women and cartilage oligomeric matrix protein as a marker of cartilage breakdown. Clin Rheumatol. 2021;40:4217–23. [DOI] [PubMed]

139.

Yazici H, Taskin MI, Guney G, Hismiogullari AA, Arslan E, Tulaci KG. The novel relationship between polycystic ovary syndrome and temporomandibular joint disorders. J Stomatol Oral Maxillofac Surg. 2021;122:544–8. [DOI] [PubMed]

140.

Soydan SS, Deniz K, Uckan S, Unal AD, Tutuncu NB. Is the incidence of temporomandibular disorder increased in polycystic ovary syndrome? Br J Oral Maxillofac Surg. 2014;52:822–6. [DOI] [PubMed]

141.

Richette P, Corvol M, Bardin T. Estrogens, cartilage, and osteoarthritis. Joint Bone Spine. 2003;70:257–62. [DOI] [PubMed]

142.

Bertacini DMM, Beleza ACS, Driusso P. The effect of parity on the function of pelvic floor musculature in the long term: cross-sectional study. Obstet Gynecol Sci. 2020;63:577–85. [DOI] [PubMed] [PMC]

143.

Junno JA, Keisu A, Niinimäki M, Niinimäki J, Lehenkari P, Oura P. Gravidity, parity and knee breadth at midlife: a population-based cohort study. Sci Rep. 2022;12:12415. [DOI] [PubMed] [PMC]

144.

Javed L, Bacha R, Khadija S, Gilani SA, Hassan M. Multiparity as a Potential Cause of the Articular Cartilage Degradation in the Knee Joint; Sonographic Evaluation in the Postmenopausal Women. Ann King Edward Med Univ. 2022;27:563–9. [DOI]

145.

Wei S, Venn A, Ding C, Martel-Pelletier J, Pelletier JP, Abram F, et al. The associations between parity, other reproductive factors and cartilage in women aged 50-80 years. Osteoarthritis Cartilage. 2011;19:1307–13. [DOI] [PubMed]

146.

Perlin B, Boyer KA. Impact of parity on biomechanical risk factors for knee OA initiation. Gait Posture. 2021;84:287–92. [DOI] [PubMed]

147.

Eslamian F, Shakouri SK, Mohammadpour N, Dolatkhah N, Bani S, Khanmiri FN. Reproductive history is associated with functional disabilities and symptoms in women with knee osteoarthritis: a case-control study. BMC Res Notes. 2024;17:196. [DOI] [PubMed] [PMC]

148.

Liu B, Balkwill A, Cooper C, Roddam A, Brown A, Beral V, et al.; Million Women Study Collaborators. Reproductive history, hormonal factors and the incidence of hip and knee replacement for osteoarthritis in middle-aged women. Ann Rheum Dis. 2009;68:1165–70. [DOI] [PubMed]

149.

Tan X, Mei Y, Zhou Y, Liao Z, Zhang P, Liu Y, et al. Causal association of menstrual reproductive factors on the risk of osteoarthritis: A univariate and multivariate Mendelian randomization study. PLoS One. 2024;19:e0307958. [DOI] [PubMed] [PMC]

150.

Liu R, Hu Y, Zhang X, Li J. Association of Reproductive Factors with Osteoarthritis and the Mediating Effect of Body Mass Index Among Postmenopausal Women. J Womens Health (Larchmt). 2025;34:1399–408. [DOI] [PubMed]

151.

Kim MY, Kim HJ, Noh JH, Kim SA, Hwang DS, Lee CH, et al. Relationship of breastfeeding duration with joint pain and knee osteoarthritis in middle-aged Korean women: a cross-sectional study using the Korea National Health and Nutrition Examination Survey. BMC Womens Health. 2020;20:213. [DOI] [PubMed] [PMC]

152.

Ham D, Bae S. Associations of breastfeeding duration and the total number of children breastfed with self-reported osteoarthritis in Korea women 50 years and older: a cross-sectional study. Epidemiol Health. 2023;45:e2023044. [DOI] [PubMed] [PMC]

153.

Williams SN, Wolford ML, Bercovitz A. Hospitalization for Total Knee Replacement Among Inpatients Aged 45 and Over: United States, 2000-2010. NCHS Data Brief. 2015:1–8. [PubMed]

154.

Shichman I, Roof M, Askew N, Nherera L, Rozell JC, Seyler TM, et al. Projections and Epidemiology of Primary Hip and Knee Arthroplasty in Medicare Patients to 2040–2060. JB JS Open Access. 2023;8:e22.00112. [DOI] [PubMed] [PMC]

155.

Tschon M, Contartese D, Pagani S, Borsari V, Fini M. Gender and Sex Are Key Determinants in Osteoarthritis Not Only Confounding Variables. A Systematic Review of Clinical Data. J Clin Med. 2021;10:3178. [DOI] [PubMed] [PMC]

156.

Whitlock KG, Piponov HI, Shah SH, Wang OJ, Gonzalez MH. Gender Role in Total Knee Arthroplasty: A Retrospective Analysis of Perioperative Outcomes in US Patients. J Arthroplasty. 2016;31:2736–40. [DOI] [PubMed]

157.

Patel AP, Gronbeck C, Chambers M, Harrington MA, Halawi MJ. Gender and Total Joint Arthroplasty: Variable Outcomes by Procedure Type. Arthroplast Today. 2020;6:517–20. [DOI] [PubMed] [PMC]

158.

Basques BA, Bell JA, Sershon RA, Della Valle CJ. The Influence of Patient Gender on Morbidity Following Total Hip or Total Knee Arthroplasty. J Arthroplasty. 2018;33:345–9. [DOI] [PubMed]

159.

Robinson J, Shin JI, Dowdell JE, Moucha CS, Chen DD. Impact of Gender on 30-Day Complications After Primary Total Joint Arthroplasty. J Arthroplasty. 2017;32:2370–4. [DOI] [PubMed]

160.

Fletcher AN, Mody KS, Adams SB Jr, DeOrio JK, Easley ME, Nunley JA. Effect of Gender Differences on Patient-Reported Outcomes and Complications in Total Ankle Replacement. Foot Ankle Int. 2021;42:776–87. [DOI] [PubMed]

161.

Perez BA, Slover J, Edusei E, Horan A, Anoushiravani A, Kamath AF, et al. Impact of gender and race on expectations and outcomes in total knee arthroplasty. World J Orthop. 2020;11:265–77. [DOI] [PubMed] [PMC]

162.

Moretti B, Spinarelli A, Varrassi G, Massari L, Gigante A, Iolascon G, et al. Influence of sex and gender on the management of late-stage knee osteoarthritis. Musculoskelet Surg. 2022;106:457–67. [DOI] [PubMed] [PMC]

163.

Borkhoff CM, Hawker GA, Wright JG. Patient gender affects the referral and recommendation for total joint arthroplasty. Clin Orthop Relat Res. 2011;469:1829–37. [DOI] [PubMed] [PMC]

164.

Hawker GA, Wright JG, Coyte PC, Williams JI, Harvey B, Glazier R, et al. Differences between men and women in the rate of use of hip and knee arthroplasty. N Engl J Med. 2000;342:1016–22. [DOI] [PubMed]