Abstract
Previous studies on the relationship between vitamin D, sleep quality, and osteoarthritis (OA) have been controversial and the aim of this study is to analyze the association. In this study, relevant data from 2 survey cycles (2009–2010 with 2011–2012) are downloaded from the CDC’s NHANES project to analyze the relationship between vitamin D, sleep quality, and osteoarthritis, as well as other related risk factors. The analysis of statistics in this study is performed using t-tests and chi-square tests, modeling is performed using logistic regression based on NHANES weights, and other risk factors are analyzed using forest plots. In association models between serum vitamin D, sleep quality, and OA is statistically significant during the stepwise inclusion of covariates. In model 1, Q3 (OR = 1.83; 95% CI: 1.05, 3.23) and Q4 (OR = 2.22; 95% CI: 1.27, 3.94) are significant. Neither model 2 nor model 3 is statistically significant and P for trend is more than .05 in all 3 models. After the inclusion of all covariates, forest plot showed that sleep deprivation (OR = 1.64; 95% CI: 1.05, 2.56), advanced age (OR = 1.03; 95% CI: 1.01, 1.04), female (OR = 1.79; 95% CI: 1.14, 2.85), overweight (25 ≤ BMI < 30) (OR = 1.92; 95% CI: 1.05, 3.61), and obesity (≥30) (OR = 2.06; 95% CI: 1.11, 3.93) are risk factors for OA. This study is based on a larger sample and a stepwise logistic regression of multiple covariates. We concluded that vitamin D may not influence OA. However other risk factors for OA are confirmed, including advanced age, female and high BMI, especially bad sleep quality.
Keywords: age, BMI, gender, NHANES, osteoarthritis, vitamin D
1. Introduction
The prevalence and impact of osteoarthritis (OA) are significant, with approximately 250 million people worldwide suffering from this degenerative joint disease, making it 1 of the leading causes of disability in the elderly.[1,2] he anticipated rise in OA incidence globally is attributed to ongoing population growth, increased life expectancy, and the growing demand for functional outcomes. By 2030, the economic burden of OA is expected to double, highlighting the need for effective management strategies.[3,4] Vitamin D insufficiency has been linked in studies to a higher risk of OA progression. In people with OA, vitamin D administration may lessen discomfort and enhance knee function.[5] Vitamin D plays a crucial role in calcium homeostasis and bone metabolism. It helps in the absorption of calcium from the intestine and its incorporation into bone, which is essential for maintaining bone density and strength. Vitamin D also regulates the function of chondrocytes, the cells responsible for producing and maintaining cartilage. It has been suggested that vitamin D insufficiency may result in the impaired production or function of chondrocytes, leading to cartilage breakdown and the progression of OA.[6]
Epidemiological studies, however, do not show evidence of an independent association between 25-hydroxyvitamin D serum levels and hip or hand OA, according to a meta-analysis.[7] Except in situations with advanced knee OA, there is little evidence to support recommendations for vitamin D supplementation to stop the onset or progression of OA.[8] According to a Mendelian randomization study, genetic variations linked to low serum vitamin D levels did not increase the incidence of hip or knee OA in older people. Supplementing with vitamin D is unlikely to stop hip or knee OA.[9]
Sleep is the most significant activities in a person’s life and essential to both health and metabolism. Several studies have revealed that sleep disruption, decreasing nociceptive hypersensitivity or endogenous pain control, plays a critical role in the manifestation of OA pain.[10,11] Studies indicate that restful sleep may lessen the effects of OA-related fatigue.[12] Sleep disruption in individuals with OA can lead to nociceptive hypersensitivity, increased inflammation, central sensitization, altered pain modulation, and psychological factors, all of which contribute to the manifestation of OA pain. Managing sleep disturbances and promoting healthy sleep hygiene can help alleviate pain and improve the overall well-being of individuals with OA.[13]
Based on previous conflicting findings, we further analyzed the relationship between vitamin D, sleep quality, and OA using a large NHANES (National Health and Nutrition Examination Survey) sample size and multiple covariates.
2. Methods
2.1. Samples
The sample for this study is drawn from data from the NHANES survey,[14–18] a large survey covering demographic, dietary, physical examination data, laboratory data, and questionnaire data. Two eligible survey cycles, 2009 to 2010 and 2011 to 2012, are selected according to the main components of the study, OA and vitamin D. These 2 survey cycles contained a sample of 20,206 individuals and after screening for missing values, the final eligible sample size is 476.
The inclusion criteria were as follows: age more than 18 years old; participants with osteoarthritis; participants received related questionnaire, examination, and laboratory test.
The exclusion criteria were as follows: lack of continuous records samples; other main outcome or exposure; lack of a lot of covariates.
2.2. Ethics approval
All participants in this study are provided with informed consent by the NHANES project and the US Centers for Disease Control and Prevention (https://www.cdc.gov/nchs/nhanes/irba98.htm#print).
2.3. osteoarthritis and included covariates
The OA data for this study are obtained from the NHANES medical condition questionnaire, for the arthritis question, with responses diagnosed as OA or non-OA. The vitamin D data are obtained from laboratory data and the experimental method is the quantitative determination of 25-hydroxyvitamin D3 (25OHD3), epi-25-hydroxyvitamin D3 (epi-25-OHD3), and 25-hydroxyvitamin D2 (25OHD2) in human serum using ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS), and we selected total 25-hydroxy vitamin D3 (25OHD3) as an indicator of serum vitamin D.
Sleep disorder questionnaire containing a limited number of questions on sleep habits and disorders is used to collect self-reported average sleep time per night from NHANES. Sleep duration < 7 h/night is defined as sleep deprivation in this study in accordance with the National Sleep Foundation’s recommendation of a normal sleep duration of 7 to 9 h/d for adults. In addition, the demographic data for this study are taken from the demographic part of the survey, and the disease history data and lifestyle data are taken from the questionnaire part.
2.4. Statistical analysis
We first performed a descriptive analysis of all covariates, grouped by the presence or absence of OA, and performed a t-test on the quantitative data and a chi-square test on the categorical data.
To analyze the relationship between OA and vitamin D, we sliced the vitamin D data into 4 quarters, which are used to see if there is a dose-response relationship. We then used logistic regression to build 3 separate models with progressive inclusion of covariates, thus verifying the stability of the relationship. After all variables are included in the models, forest plots of the relationship between all OA and covariates are produced so that other risk factors that may be associated with OA could be analyzed. All analyzes in this study are performed by R4..2.2 (R Core Team, Vienna, Austria) and P < .05 is considered statistically significant.
3. Results
Table 1 shows all the covariates for the 2 groups, OA and non-OA, and it can be seen that some indicators are higher in the OA group than in the non-OA group, including vitamin D, sleep quality, age, percentage of females, and percentage of whites. For other covariates, the differences between the 2 groups are not statistically significant. This difference provides a basis for exploring the relationship between vitamin D, sleep quality, and OA.
Table 1.
Characteristics of included samples.
| Non-OA (N = 324) | OA (N = 152) | P | |
|---|---|---|---|
| Vitamin D | 65.3 (27.5) | 74.5 (30.9) | .002 |
| Age | 59.3 (14.7) | 64.2 (13.5) | <.001 |
| Sleep quality | |||
| Sufficient | 187 (57.7%) | 81 (53.3%) | .419 |
| Deprivation | 137 (42.3%) | 71 (46.7%) | |
| Gender | |||
| Male | 162 (50.0%) | 58 (38.2%) | .02 |
| Female | 162 (50.0%) | 94 (61.8%) | |
| BMI | |||
| Normal (<25) | 70 (21.6%) | 22 (14.5%) | .158 |
| Overweight (25 ≤ BMI < 30) | 154 (47.5%) | 75 (49.3%) | |
| Obesity (≥30) | 100 (30.9%) | 55 (36.2%) | |
| Race | |||
| Mexican American | 42 (13.0%) | 11 (7.24%) | .006 |
| Other Hispanic | 20 (6.17%) | 9 (5.92%) | |
| Non-Hispanic White | 186 (57.4%) | 113 (74.3%) | |
| Non-Hispanic Black | 67 (20.7%) | 16 (10.5%) | |
| Other race | 9 (2.78%) | 3 (1.97%) | |
| Education | |||
| <9th grade | 40 (12.3%) | 12 (7.89%) | .065 |
| 9–11th grade | 64 (19.8%) | 25 (16.4%) | |
| High school | 89 (27.5%) | 34 (22.4%) | |
| Some college | 89 (27.5%) | 49 (32.2%) | |
| College graduate or above | 42 (13.0%) | 31 (20.4%) | |
| Missing | 0 (0.00%) | 1 (0.66%) | |
| Marital status | |||
| Married | 173 (53.4%) | 82 (53.9%) | .809 |
| Widowed | 51 (15.7%) | 26 (17.1%) | |
| Divorced | 46 (14.2%) | 26 (17.1%) | |
| Separated | 5 (1.54%) | 3 (1.97%) | |
| Never married | 32 (9.88%) | 10 (6.58%) | |
| Living with partner | 16 (4.94%) | 5 (3.29%) | |
| Refused | 1 (0.31%) | 0 (0.00%) | |
| PIR | 2.46 (1.59) | 2.76 (1.59) | .055 |
| Smoking | |||
| Yes | 209 (64.5%) | 93 (61.2%) | .549 |
| No | 115 (35.5%) | 59 (38.8%) | |
| Alcohol | |||
| Yes | 80 (24.7%) | 27 (17.8%) | .116 |
| No | 244 (75.3%) | 125 (82.2%) | |
| Diabetes | |||
| Yes | 64 (19.8%) | 30 (19.7%) | .998 |
| No | 249 (76.9%) | 117 (77.0%) | |
| Borderline | 11 (3.40%) | 5 (3.29%) | |
| Hypertension | |||
| Yes | 7 (2.16%) | 5 (3.29%) | .533 |
| No | 317 (97.8%) | 147 (96.7%) | |
Table 2 shows that in all 3 models there is no dose-response relationship (P for trend > .05), Q3 (OR = 1.83; 95% CI: 1.05, 3.23) and Q4 (OR = 2.22; 95% CI: 1.27, 3.94) is statistically significant in model 1, OR is not statistically significant in any of model 2, and OR is not statistically significant in any of model 3 after inclusion of all covariates. This suggests that vitamin D may not be a risk or protective factor for OA.
Table 2.
Logistic risk analysis for vitamin D and OA.
| Serum vitamin D (nmol/L) | Model 1 | Model 2 | Model 3 |
|---|---|---|---|
| Q1 (4–46.2) | Reference | Reference | Reference |
| Q2 (46.2–61.9) | 1.07 (0.59, 1.95) | 0.98 (0.5, 1.9) | 0.99 (0.51, 1.94) |
| Q3 (61.9–78.1) | 1.83 (1.05, 3.23)* | 1.32 (0.69, 2.55) | 1.29 (0.67, 2.5) |
| Q4 (78.1–375) | 2.22 (1.27, 3.94)* | 1.32 (0.67, 2.61) | 1.32 (0.67, 2.63) |
| P trend | .03 | .04 | .01 |
P < .05, model 1 = no adjust; model 2 = as model 1 plus adjusted for sex, age (years, continuous), age squared, education (less than high school, high school graduate, some college and above), race (non-Hispanic White, non-Hispanic Black, Mexican American, other), self-reported alcohol status (yes and no) and self-reported smoking status (yes and no); model 3 = model 2 plus adjusted for BMI, self-reported hypertension (yes and no) and self-reported diabetes (yes and no).
On the basis of model 3, all variables are pooled and forest plots are drawn. It can be seen that vitamin D is not statistically significant at Q2, Q3, and Q4 levels, suggesting that vitamin D may not be associated with OA. However, sleep quality had association with OA that sleep deprivation (OR = 1.64; 95% CI: 1.05, 2.56) contributed to OA. In addition, age (OR = 1.03; 95% CI: 1.01, 1.04), female (OR = 1.79; 95% CI: 1.14, 2.85), overweight (25 ≤ BMI < 30) (OR = 1.92; 95% CI: 1.05, 3.61), and obesity (≥30) (OR = 2.06; 95% CI: 1.11, 3.93) are risk factors for OA (Fig. 1).
Figure 1.
Forest plot for risk factors of osteoarthritis. LBXVIDMSQ: serum vitamin D; SLPQ: sleep quality; RIDAGEYR: age; RIAGENDR: gender (1 = male, 2 = female); RIDRETH1: race (1 = Mexican American, 2 = other Hispanic, 3 = non-Hispanic White, 4 = non-Hispanic Black, 5 = other race – including multi-racial), DMDEDUC2: education (1 = <9th grade, 2 = 9–11th grade, 3 = high school grad/GED or equivalent, 4 = some college or AA degree, 5 = college graduate or above); DMDMARTL: marriage (1 = married, 2 = widowed, 3 = divorced, 4 = separated, 5 = never married, 6 = living with partner); BMIQ: BMI (1 = normal [<25], 2 = overweight [25 ≤ BMI < 30], 3 = obesity [≥30]); SMQ020: smoking (1 = no, 2 = yes); ALQ151: alcohol (1 = No, 2 = Yes); DIQ010: diabetes (1 = no, 2 = yes, 3 = borderline, 9 = missing); HYTQ (1 = no, 2 = yes).
4. Discussion
The results of the current study suggest that serum vitamin D levels may not reduce the risk of OA, unlike the previous extensive reports that oral vitamin D supplementation may be prepaid for the treatment of OA. This may be due to the fact that serum vitamin D levels are not equated with the dose of oral vitamin D. Patients who have taken oral vitamin D supplements may be influenced by other factors that weaken or enhance the absorption of vitamin D, resulting in inconsistencies between serum vitamin D and vitamin D supplement doses. Our findings, of course, are consistent with some other previous reports. According to a McAlindon et al trial[19] that is published in JAMA in 2013, vitamin D supplementation at doses that increased plasma levels of 250 HD to > 36 ng/ml did not, compared to a placebo, lessen knee discomfort or cartilage volume loss after 2 years. According to a 2016 study by Jin et al published in JAMA,[20] vitamin D supplementation did not significantly differ from a placebo in terms of changes in tibial cartilage volume assessed by MRI or WOMAC knee pain scores over a 2-year period in patients with knee OA and low serum 25-hydroxyvitamin D levels. This study did not support the use of vitamin D supplementation to stop cartilage loss or reduce WOMAC knee pain in patients with knee OA. The impact of vitamin D on OA has not been determined by in vitro research. 1,25(OH)2D enhanced the expression of Mmp13 RNA and protein in ATDC5 and rat chondrosarcoma chondrocytes in a time- and dose-dependent manner.[21,22] Contrarily, 1,25(OH)2D suppressed the expression of type II collagen and aggregated proteoglycan, suggesting that vitamin D may cause or aggravate OA,[23] which is consistent with our findings.
In this research, sleep deprivation is a risk factor for OA. Uncertain mechanisms underlie the connection between OA pain and sleep/fatigue. Although OA pain can alter sleep and insufficient sleep can worsen OA pain perception, the relationship is complicated and may be bidirectional.[24] According to a study by the OATS, improved sleep hygiene can effectively treat insomnia in persons who have pain by reducing their OA discomfort over the long run, enhancing depression and weariness, and increasing sleep in the process.[10]
It was reported that obstructive sleep apnea influences OA progression through a shared inflammatory pathway, particularly involving the TNF signaling cascade. This connection underscores the importance of addressing sleep disturbances in patients with OA and highlights potential therapeutic targets for managing both conditions.[25] Further research may clarify the roles of specific miRNAs and the efficacy of proposed drug interventions in clinical settings. While cognitive Behavioral Therapy for Insomnia shows promise in improving sleep disturbances in individuals with knee OA and insomnia, it does not appear to significantly reduce IL-6 levels or systemic inflammation. Sleep impairment is a significant concern in rheumatoid arthritis, influenced by complex interactions between inflammation, pain, comorbidities, and medications.[26] The consequences extend beyond sleep quality, affecting overall health and quality of life. A thorough understanding of these relationships is essential for developing effective management strategies to improve sleep and, consequently, the well-being of RA patients.[27] Further research is warranted to elucidate the mechanisms involved and optimize treatment approaches.
On this basis, we again validated that advanced age, female, and high BMI are all risk factors for OA, which is consistent with previous reports. Age has a beneficial impact on the risk of OA of the hip and knee in women, according to research on the relationship between age, gender, and OA affecting other joints.[28] Women often have smaller femoral head diameters, greater anterior femoral neck inclination, and greater acetabular anteversion and tilt when it comes to gender differences in hip anatomy.[29] There is evidence to show that worse hip alignment and the subsequent development of OA are caused by increased acetabular anteversion along the femur. In addition, postmenopausal women’s reduced estrogen levels could age-related illness progression.
A second investigation into the relationship between obesity and OA revealed that class II obesity (a BMI of 35 kg/m2 or higher) is related with a higher risk of OA in the knee, hip, and hand in individuals.[30] As comparison to those who are of normal weight, class II obese people had a 4.7-fold higher risk of developing knee OA. Leptin may be connected to this phenomenon (LEP). It has been proposed that high BMI is highly correlated with greater LEP promoter methylation levels in patients with OA, and that this link is especially strong in obese patients with OA.[31]
This study has the advantage of including a large sample size and a number of covariates for analysis. However, there are still some limitations of this study. Firstly, the study fails to fully explain the reasons for the failure of vitamin D to affect OA from a mechanistic perspective. Secondly, the survey data used in this study are derived from cross-sectional studies and cannot be used as a basis for causality inference. Finally, the covariates not included in this study may also affect OA.
In conclusion, based on a larger sample and multiple covariates, the analysis in this study concluded that vitamin D may not influence the occurrence of OA, but other risk factors for OA are confirmed, including sleep deprivation, advanced age, female and high BMI.
Author contributions
Data curation: Yaqi Gong.
Formal analysis: Xuan Zhou, Yaqi Gong.
Methodology: Xuan Zhou.
Software: Yaqi Gong.
Validation: Yaqi Gong.
Writing – original draft: Xuan Zhou.
Writing – review & editing: Yaqi Gong.
Abbreviations:
- BMI
- body mass index
- IL-6
- interleukin-6
- MRI
- magnetic resonance imaging
- NHANES
- National Health and Nutrition Examination Survey
- OA
- osteoarthritis
- RA
- rheumatoid arthritis
- TNF
- tumor necrosis factor
- WOMAC
- the Western Ontario and McMaster universities osteoarthritis index
The authors have no funding and conflicts of interest to disclose.
The datasets generated during and/or analyzed during the current study are publicly available.
How to cite this article: Zhou X, Gong Y. Exploration in association between vitamin D, sleep quality, and osteoarthritis: A modeling study. Medicine 2024;103:40(e40021).
References
- [1].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] [PMC free article] [PubMed] [Google Scholar]
- [2].Bergink AP, Zillikens MC, Van Leeuwen JPTM, Hofman A, Uitterlinden AG, van Meurs JBJ. 25-Hydroxyvitamin D and osteoarthritis: a meta-analysis including new data. Semin Arthritis Rheum. 2016;45:539–46. [DOI] [PubMed] [Google Scholar]
- [3].Chua JR, Shakeel J, Mariam R, et al. Disease burden in osteoarthritis is similar to that of rheumatoid arthritis at initial rheumatology visit and significantly greater six months later. Arthritis Rheumatol. 2019;71:1276–84. [DOI] [PubMed] [Google Scholar]
- [4].Grotle M, Hagen KB, Natvig B, Dahl FA, Kvien TK. Prevalence and burden of osteoarthritis: results from a population survey in Norway. J Rheumatol. 2008;35:677–84. [PubMed] [Google Scholar]
- [5].Li H, Liu Y, Zhang R-J, Ding J-Y, Shen C-L. Vitamin D receptor gene polymorphisms and osteoarthritis: a meta-analysis. Rheumatology (Oxford). 2021;60:538–48. [DOI] [PubMed] [Google Scholar]
- [6].Zhang FF, Driban JB, Lo GH, et al. Vitamin D deficiency is associated with progression of knee osteoarthritis. J Nutr. 2014;144:2002–8. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [7].Hussain S, Singh A, Akhtar M, Najmi AK. Vitamin D supplementation for the management of knee osteoarthritis: a systematic review of randomized controlled trials. Rheumatol Int. 2017;37:1489–98. [DOI] [PubMed] [Google Scholar]
- [8].Manoy P, Yuktanandana P, Tanavalee A, et al. Vitamin D supplementation improves quality of life and physical performance in osteoarthritis patients. Nutrients. 2017;9:799. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [9].Bergink AP, Trajanoska K, Uitterlinden AG, van Meurs JBJ. Mendelian randomization study on vitamin D levels and osteoarthritis risk: a concise report. Rheumatology (Oxford). 2021;60:3409–12. [DOI] [PubMed] [Google Scholar]
- [10].Wu Z, Hu H, Wang C, et al. Sleep patterns modify the association between vitamin D status and coronary heart disease: results from NHANES 2005–2008. J Nutr. 2023;153:1398–406. [DOI] [PubMed] [Google Scholar]
- [11].Fu K, Makovey J, Metcalf B, et al. Sleep quality and fatigue are associated with pain exacerbations of hip osteoarthritis: an internet-based case-crossover study. J Rheumatol. 2019;46:1524–30. [DOI] [PubMed] [Google Scholar]
- [12].Doo M. The association between sleep duration and 25-hydroxyvitamin D concentration with obesity in an elderly Korean population: a cross-sectional study. Nutrients. 2018;10:575. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [13].Parmelee PA, Tighe CA, Dautovich ND. Sleep disturbance in osteoarthritis: linkages with pain, disability, and depressive symptoms. Arthritis Care Res (Hoboken). 2015;67:358–65. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [14].Shi J, Yin C, Wu J. Possible non-linear relation between prostate specific antigen and vitamin D: a machine learning study based on cross-section data. J Cancer. 2024;15:3625–32. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [15].Ren L, Zhang Y, Wu J. Association between urinary metals and prostate-specific antigen in aging population with depression: a cross-sectional study. Front Public Health. 2024;12:1401072. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [16].Tao Q, Chang Y, Day AS, Wu J, Wang X. Association between serum 25-hydroxyvitamin D level and myopia in children and adolescents: a cross-sectional study. Transl Pediatr. 2024;13:310–7. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [17].Zhang Y, Wang K, Zhu J, Wu J. A network suspected infectious disease model for the development of syphilis transmission from 2015 to 2021 in Hubei province, China. J Appl Microbiol. 2023;134:lxad311. [DOI] [PubMed] [Google Scholar]
- [18].Jinyi W, Zhang Y, Wang K, Peng P. Global, regional, and national mortality of tuberculosis attributable to alcohol and tobacco from 1990 to 2019: a modelling study based on the global burden of disease study 2019. J Glob Health. 2024;14:04023. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [19].McAlindon T, LaValley M, Schneider E, et al. Effect of vitamin D supplementation on progression of knee pain and cartilage volume loss in patients with symptomatic osteoarthritis. JAMA. 2013;309:155–62. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [20].Jin X, Jones G, Cicuttini F, et al. Effect of vitamin D supplementation on tibial cartilage volume and knee pain among patients with symptomatic knee osteoarthritis. JAMA. 2016;315:1005–13. [DOI] [PubMed] [Google Scholar]
- [21].Zhao Z, He Y, Peng L-H, et al. Does vitamin D improve symptomatic and structural outcomes in knee osteoarthritis? A systematic review and meta-analysis. Aging Clin Exp Res. 2021;33:2393–403. [DOI] [PubMed] [Google Scholar]
- [22].Nakamura K, Hui S-P, Ukawa S, et al. Serum 25-hydroxyvitamin D3 levels and poor sleep quality in a Japanese population: the DOSANCO Health Study. Sleep Med. 2019;57:135–40. [DOI] [PubMed] [Google Scholar]
- [23].Park CY. Vitamin D in the prevention and treatment of osteoarthritis: from clinical interventions to cellular evidence. Nutrients. 2019;11:243. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [24].Vitiello MV, Zhu W, Von Korff M, et al. Long-term improvements in sleep, pain, depression, and fatigue in older adults with comorbid osteoarthritis pain and insomnia. Sleep. 2022;45:zsab231. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [25].Ren XS, Xie T, Zhuang HM, Lei TR, Jiang FZ, Zhou PH. The molecular link between obstructive sleep apnea and osteoarthritis: based on bioinformatics analysis and experimental validation. Am J Transl Res. 2023;15:4487–503. [PMC free article] [PubMed] [Google Scholar]
- [26].Coskun Benlidayi I. Sleep impairment: an obstacle to achieve optimal quality of life in rheumatoid arthritis. Rheumatol Int. 2018;38:2183–92. [DOI] [PubMed] [Google Scholar]
- [27].Mun CJ, Speed TJ, Finan PH, Wideman TH, Quartana PJ, Smith MT. A preliminary examination of the effects and mechanisms of cognitive behavioral therapy for insomnia on systemic inflammation among patients with knee osteoarthritis. Int J Behav Med. 2024;31:305–14. [DOI] [PubMed] [Google Scholar]
- [28].Yan Y, Qu Z, Yu D-Q, Wang W, Yan S, Huang H-F. Sex steroids and osteoarthritis: a Mendelian randomization study. Front Endocrinol. 2021;12:683226. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [29].Peshkova M, Lychagin A, Lipina M, et al. Gender-related aspects in osteoarthritis development and progression: a review. Int J Mol Sci. 2022;23:2767. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [30].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] [PMC free article] [PubMed] [Google Scholar]
- [31].Yang T, Chen H-M, Hu C-C, et al. Interaction of osteoarthritis and BMI on leptin promoter methylation in Taiwanese adults. Int J Mol Sci. 2020;21:123. [DOI] [PMC free article] [PubMed] [Google Scholar]