Research Article

The Mediating Role of Functional Limitations Between Recurrent Falls and Knee Osteoarthritis: An Observational Study Based on CHARLS 2015

DOI:

10.3791/70456

⸱

June 16th, 2026

 ,  ,  ,  ,  ,  ,  ,  ,  ,  ,  , 
1International Department of Orthopedics, Hospital of Chengdu University of Traditional Chinese Medicine, 2School of Orthopedics, Henan University of Chinese Medicine, 3School of Traditional Chinese Medicine, Hubei University of Chinese Medicine, 4General Medicine Department, Hospital of Chengdu University of Traditional Chinese Medicine

In This Article

Summary

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This cross-sectional observational mediation analysis suggests that functional limitations partially mediate the association between recurrent falls and knee osteoarthritis, highlighting the importance of fall prevention and functional maintenance in middle-aged and older adults.

Abstract

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Studies on the relationships among functional limitations, recurrent falls, and knee osteoarthritis remain limited. This cross-sectional observational study examined the associations among recurrent falls, functional limitations, and knee osteoarthritis and evaluated whether functional limitations mediated the relationship between recurrent falls and knee osteoarthritis. After excluding participants younger than 45 years and those with missing data for core variables and covariates, 2,278 participants from the CHARLS 2015 survey were included in complete-case analysis. Spearman correlation analysis was used to assess the correlations among recurrent falls, functional limitation score, and knee osteoarthritis. Because knee osteoarthritis was treated as a binary outcome, multivariable logistic regression was used to evaluate its association with recurrent falls. Mediation analysis was performed within a bootstrap mediation framework based on a linear mediator model and a logistic outcome model, with recurrent falls as the independent variable, functional limitation score as the mediator, and knee osteoarthritis as the dependent variable. Recurrent falls were significantly associated with higher odds of knee osteoarthritis in the adjusted model. After the functional limitation score was added to the model, recurrent falls remained significantly associated with knee osteoarthritis, and the functional limitation score was also significantly associated with knee osteoarthritis. Bootstrap mediation analysis showed a total effect of 0.093 (95% CI: 0.050–0.138), a direct effect of 0.079 (95% CI: 0.037–0.123), and an indirect effect through functional limitations of 0.014 (95% CI: 0.006–0.023), accounting for 14.92% of the total effect. These findings support a statistically significant mediation pattern in which functional limitations serve as an intermediate factor in the association between recurrent falls and knee osteoarthritis. These results highlight the importance of integrating fall-risk assessment and functional status evaluation into health management for knee osteoarthritis in middle-aged and older adults.

Introduction

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Knee osteoarthritis (KOA) is a common degenerative joint disease that usually manifests as knee pain, limited mobility, and joint stiffness1,2,3. With the prolonged course of the disease, patients often experience dysfunction of the knee joint, and in severe cases, they even lose the ability to perform daily activities4,5. Knee osteoarthritis has a high epidemiologic burden worldwide, and it is especially common in the elderly population6,7,8. It is estimated that approximately 13% of individuals aged 60 years or older have knee osteoarthritis, and its prevalence tends to increase significantly with age9. Knee osteoarthritis imposes a significant burden on individuals, families, and society10,11. At the societal level, knee osteoarthritis not only increases healthcare resource consumption but also significantly reduces labor productivity, thereby increasing the socioeconomic burden12,13,14. Mechanistically, knee osteoarthritis is a multifactorial disease involving biological, biomechanical, inflammatory, metabolic, and post-traumatic pathways, including age-related degeneration and injury-related joint instability or abnormal loading. Therefore, it is necessary to conduct relevant studies on knee osteoarthritis to clarify its associated factors, especially modifiable factors related to mobility, joint loading, and functional decline.

Recurrent falls have received increasing research attention in recent years and are prevalent in the elderly population15,16,17. Falls not only increase the risk of injury in older adults, which may lead to conditions such as fractures or head trauma, but may also cause long-term functional impairment in older adults, leading to functional limitations and a reduced quality of life, and may also lead to the development of knee osteoarthritis18,19,20. Studies have shown that falls occur in approximately 25% of older adults each year21,22,23. In addition, as the population ages, the incidence of falls and the resulting socioeconomic costs continue to rise. This not only tests families' affordability but also places tremendous pressure on the public health system24,25. In the pathological context of knee osteoarthritis, recurrent falls are relevant not only because of acute injury, but also because fall-related pain, joint injury, gait instability, and fear of falling may reduce activity participation and alter lower-limb loading patterns26,27. Therefore, how to reduce the incidence of falls, especially to avoid recurrent falls in elderly individuals, has become an urgent issue.

Functional limitations are often related to chronic joint loading, restricted movement, and altered movement patterns. Functional limitations of the knee joint in elderly individuals may directly affect the loading capacity of the knee joint, with long-term abnormal loading and degenerative changes in the joint triggering the development of knee osteoarthritis28,29,30. Functional limitations may further influence knee osteoarthritis-related health burden by reducing periarticular muscle support, impairing dynamic knee stability, and promoting compensatory gait patterns; these changes may increase mechanical stress on cartilage, meniscus, subchondral bone, and periarticular soft tissues. In addition, studies have shown that long-term recurrent falls not only lead directly to physical injuries but also may aggravate functional limitations, which in turn affect quality of life and may lead to the development of knee osteoarthritis31,32. Therefore, functional limitations may play an important mediating role in the relationship between recurrent falls and knee osteoarthritis, and may act as a functional bridge between fall-related mobility decline and knee osteoarthritis-related health burden.

Therefore, this study aimed to examine whether functional limitations mediate the association between recurrent falls and knee osteoarthritis among middle-aged and older Chinese adults, thereby providing evidence for fall prevention and functional maintenance in knee osteoarthritis-related health management.

Protocol

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Data
The CHARLS database is based on a survey of health, economic, and social activities in China33. All the CHARLSs received ethical approval from the Institutional Review Board (IRB) of Peking University. The IRB approval number for the main household survey (including anthropometrics) was IRB0000105211015. In the current study, the authors applied the 2015 survey. The sample consisted of 21,095 participants. Participants aged ≤45 years or with missing age information were excluded. Participants with missing data for the three core variables, recurrent falls, functional limitation score, and knee osteoarthritis, were then excluded. Finally, participants with missing covariate data were further excluded to construct a complete-case analytical dataset. All the materials and tools used for this study are listed in the Table of Materials.

Key variable indicators

Recurrent falls
Fall was a participant self-reported outcome34, which was assessed on the basis of "Have you experienced any falls since your last visit?" The participants provided binary responses, indicating either "yes" or "no." In the present analysis, participants who answered “yes” were classified as having recurrent falls, and those who answered “no” were classified as not having recurrent falls.

Knee osteoarthritis
The outcome of symptomatic knee osteoarthritis was determined if the participant answered "yes" to the first of the following questions and "knee" to the second question35 : “Are you often troubled with any body pain?” and “On what part of your body do you feel pain? Please list all parts of the body you are currently feeling pain in.” Thus, knee osteoarthritis in this study was operationalized using self-reported knee pain information from CHARLS 2015. This definition was used because, owing to the data-collection design of CHARLS 2015, radiographic assessment and physician-diagnosed knee osteoarthritis were not available in the dataset used for this analysis.

Functional limitations
Functional limitations were assessed using activities of daily living (ADL) and instrumental activities of daily living (IADL) items from CHARLS 201536. ADL items included difficulties in dressing, bathing, eating, getting in and out of bed, toileting, and controlling urination and defecation. IADL items included difficulties in housework, cooking, shopping, managing money, and taking medication. Each item was scored on a four-point scale from 1, indicating no difficulty, to 4, indicating inability to perform the activity. The 11 ADL and IADL items were summed to generate a functional limitation score ranging from 11 to 44. Higher scores indicated more severe functional limitations. The functional limitation score was treated as a continuous mediator in the mediation analysis. In addition, ADL disability and IADL disability were constructed as binary covariates. ADL disability was coded as present if the participant reported being unable to perform at least one ADL activity. IADL disability was coded as present if the participant reported being unable to perform at least one IADL activity. These two binary variables were included as covariates in the regression models, whereas the summed functional limitation score was used as the mediator.

Covariates
The covariates included sex, age, drinking status, smoking status, body mass index category, night sleep duration, depression status, cognition score, ADL disability, and IADL disability. Sex was categorized as male or female. Age was analyzed as a continuous variable. Drinking status was coded as yes if participants reported drinking alcoholic beverages, either more than once per month or less than once per month, and no if they reported no alcohol consumption. Smoking status was coded as yes if participants reported a history of smoking and no otherwise. Body mass index was categorized as underweight, normal, overweight, or obese. Night sleep duration was categorized as <6 h or ≥6 h.

Depression status was assessed using the 10-item depressive symptom scale from CHARLS 201537. The items asked whether, during the past week, participants were bothered by things that usually did not bother them, had difficulty concentrating, felt depressed, felt that everything was an effort, felt hopeful about the future, felt fearful, had restless sleep, felt happy, felt lonely, or could not get going. Each item was originally scored on a four-point frequency scale from 1 to 4. For the eight negatively worded items, responses were converted to scores from 0 to 3 by subtracting 1 from the original response. The two positively worded items, feeling hopeful about the future and feeling happy, were reverse-scored. The total depression score ranged from 0 to 30, with higher scores indicating more severe depressive symptoms. Participants were categorized into depression score <10 and ≥10 groups, with a score ≥10 indicating a higher depressive symptom burden.

Cognition score was calculated using cognition-related items from CHARLS 201538. These items included correct identification of the year, month, date, day of the week, and season; five serial subtraction tasks; and a figure-drawing task. For the serial subtraction task, participants were asked to subtract 7 from 100 in successive steps, and correct answers to the five steps were scored separately. Correct responses were scored as 1 and incorrect responses as 0. The total cognition score was calculated by summing all item scores, with a possible range from 0 to 11. Higher scores indicated better cognitive performance.

Statistical analysis
First, a complete-case analytical dataset was constructed by excluding participants younger than 45 years and those with missing data for recurrent falls, functional limitation score, knee osteoarthritis, or covariates included in the regression models. The characteristics of the study population were summarized as means and standard deviations for continuous variables and frequencies and percentages for categorical variables. Baseline characteristics were compared between female and male participants using Student’s t-test for continuous variables and chi-square tests for categorical variables. Spearman correlation analysis was performed to examine the correlations among recurrent falls, functional limitation score, and knee osteoarthritis.

Because knee osteoarthritis was treated as a binary outcome, multivariable logistic regression was used to examine the association between recurrent falls and knee osteoarthritis. The functional limitation score was treated as a continuous mediator; therefore, linear regression was used to evaluate the association between recurrent falls and the functional limitation score. Model 1 included recurrent falls as the main independent variable and adjusted for sex, age, drinking status, smoking status, body mass index category, night sleep duration, depression status, cognition score, ADL disability, and IADL disability. Model 2 included the same covariates as Model 1 and additionally included the functional limitation score.

The mediation analysis was conducted using a bootstrap mediation framework based on a linear mediator model and a logistic outcome model. In this model, recurrent falls were defined as the independent variable, functional limitation score as the mediator, and knee osteoarthritis as the dependent variable. The mediation analysis estimated the indirect effect, direct effect, total effect, and proportion mediated. Path a represented the association between recurrent falls and functional limitation score, and path b represented the association between functional limitation score and knee osteoarthritis after adjustment for recurrent falls and covariates. The direct effect represented the association between recurrent falls and knee osteoarthritis after functional limitation score was included in the model.

Bootstrap resampling with 5,000 simulations was used to estimate the total, direct, and indirect effects and their 95% confidence intervals. The authors used 5,000 bootstrap simulations to improve the stability of confidence interval estimation for the indirect effect, which is often non-normally distributed. The mediation effect was considered statistically significant when the 95% bootstrap confidence interval did not include zero. Statistical significance was defined as a two-sided p value <0.0539.

All statistical analyses were conducted using R software version 4.4.1 on Windows 10 x64. The main R packages used included tidyverse version 2.0.0, dplyr version 1.1.4, tableone version 0.13.2, psych version 2.5.6, mediation version 4.5.1, and ggplot2 version 3.4.4. Data extraction and variable construction were performed using prespecified R scripts according to the CHARLS 2015 variable dictionary and questionnaire documentation. Reproducibility was ensured by using prespecified scripts and recording the R session information. Statistical analyses were performed by the study authors, and the analytical outputs were checked against the generated tables and figures. In addition, the statistical workflow, model selection, and main analytical outputs were reviewed by a professor with expertise in statistical methodology from the author’s university to further ensure the appropriateness and reliability of the analyses.

Results

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Characteristics of participants
The study population was selected through the screening process shown in Figure 1. A total of 21,095 participants from the CHARLS 2015 survey were initially screened. After excluding 1,934 participants aged ≤45 years or with missing age information, 19,161 participants remained. Among them, 6,572 participants were excluded due to missing data on recurrent falls, functional limitation score, or knee osteoarthritis, and 10,311 were further excluded due to missing covariate data. The final complete-case analytical sample included 2,278 participants. The basic characteristics of the study sample are shown in Table 1. Among the final participants, 1,759 were female, and 519 were male. The mean age was 58.6 years overall, 57.9 years in females, and 61.0 years in males, with a significant sex difference (p < 0.001). Compared with females, males had higher proportions of drinking and smoking. BMI category also differed significantly by sex (p = 0.002). Knee osteoarthritis was more common in females than in males (20.6% vs. 12.1%, p < 0.001). Females had higher depression scores and a higher proportion of depression scores ≥10, whereas males had higher cognition scores.

Correlations between key variables
Table 2 shows the Spearman correlations among recurrent falls, functional limitation score, and knee osteoarthritis. Recurrent falls were positively correlated with functional limitation score (r = 0.148, p < 0.001), and functional limitation score was positively correlated with knee osteoarthritis (r = 0.274, p < 0.001). Recurrent falls were also positively correlated with knee osteoarthritis (r = 0.146, p < 0.001).

Exploring the mediating role of functional limitations
As shown in Table 3, recurrent falls were significantly associated with higher odds of knee osteoarthritis in Model 1 after adjustment for covariates (OR = 1.87, 95% CI: 1.44–2.43, p < 0.001). As shown in Table 4, after the functional limitation score was added to Model 2, recurrent falls remained significantly associated with knee osteoarthritis (OR = 1.70, 95% CI: 1.30–2.23, p < 0.001). Functional limitation score was also significantly associated with knee osteoarthritis (OR = 1.26, 95% CI: 1.18–1.34, p < 0.001). These findings indicate that functional limitations partially accounted for the association between recurrent falls and knee osteoarthritis.

As shown in Table 5, bootstrap mediation analysis further showed that the total effect of recurrent falls on knee osteoarthritis was 0.093 (95% CI: 0.050–0.138). The indirect effect through functional limitations was 0.014 (95% CI: 0.006–0.023), and the direct effect was 0.079 (95% CI: 0.037–0.123). Functional limitations accounted for 14.92% of the total effect. The mediation pathway model is shown in Figure 2.

DATA AVAILABILITY:
The data supporting the findings of this study are from the CHARLS. These data are publicly available and can be accessed by registered researchers through the CHARLS official website (https://charls.pku.edu.cn). The present study involved only secondary analysis; no new data were collected, and data ownership remains with the original data custodians.

Flowchart illustrating participant selection process, exclusions, and final sample size.
Figure 1: Flowchart of participant selection from the CHARLS 2015 survey. Flowchart illustrating the participant selection process from the CHARLS 2015 survey and the final study sample included in the analysis. Please click here to view a larger version of this figure.

Functional limitations mediation diagram; recurrent falls, knee osteoarthritis analysis with CI values.
Figure 2: Functional limitations mediate the relationship between recurrent falls and knee osteoarthritis. Mediation model showing that functional limitations mediate the association between recurrent falls and knee osteoarthritis. Please click here to view a larger version of this figure.

CharacteristicOverall (n = 2,278)Female (n = 1,759)Male (n = 519)p value
Age, years, mean (SD)58.6 (9.0)57.9 (8.5)61.0 (10.2)<0.001
Drinking, n (%)<0.001
No1752 (76.9)1510 (85.8)242 (46.6)
Yes526 (23.1)249 (14.2)277 (53.4)
Smoking, n (%)<0.001
No2068 (90.8)1731 (98.4)337 (64.9)
Yes210 (9.2)28 (1.6)182 (35.1)
BMI category, n (%)0.002
Normal1128 (49.5)844 (48.0)284 (54.7)
Obesity192 (8.4)166 (9.4)26 (5.0)
Overweight849 (37.3)668 (38.0)181 (34.9)
Underweight109 (4.8)81 (4.6)28 (5.4)
Knee osteoarthritis, n (%)<0.001
No1852 (81.3)1396 (79.4)456 (87.9)
Yes426 (18.7)363 (20.6)63 (12.1)
Night sleep duration, n (%)0.001
<6 h732 (32.1)596 (33.9)136 (26.2)
≥6 h1546 (67.9)1163 (66.1)383 (73.8)
ADL disability, n (%)0.286
No2237 (98.2)1724 (98.0)513 (98.8)
Yes41 (1.8)35 (2.0)6 (1.2)
IADL disability, n (%)0.858
No2176 (95.5)1679 (95.5)497 (95.8)
Yes102 (4.5)80 (4.5)22 (4.2)
Functional limitation score, mean (SD)12.0 (2.3)12.0 (2.4)11.8 (2.1)0.153
Recurrent falls, n (%)0.008
No1875 (82.3)1427 (81.1)448 (86.3)
Yes403 (17.7)332 (18.9)71 (13.7)
Depression score, mean (SD)8.0 (6.0)8.3 (6.2)7.0 (5.4)<0.001
Depression score group, n (%)<0.001
<101508 (66.2)1121 (63.7)387 (74.6)
≥10770 (33.8)638 (36.3)132 (25.4)
Cognition score, mean (SD)7.1 (2.0)6.9 (2.0)7.4 (1.8)<0.001

Table 1: Basic characteristics of the study sample by sex. Demographic, lifestyle, and health-related characteristics of the study participants stratified by sex. Values are presented as mean (SD) for continuous variables and n (%) for categorical variables. Abbreviations; BMI = body mass index; ADL = activities of daily living; IADL = instrumental activities of daily living.

VariableRecurrent fallsFunctional limitation scoreKnee osteoarthritis
Recurrent falls1
Functional limitation score0.148***1
Knee osteoarthritis0.146***0.274***1

Table 2: Spearman correlations among recurrent falls, functional limitation score, and knee osteoarthritis. Spearman correlation coefficients showing the relationships among recurrent falls, functional limitation score, and knee osteoarthritis. ***p < 0.001. Spearman correlation coefficients are shown in the lower triangle.

βSEOR (95% CI)p value
Recurrent falls (yes vs. no)0.6250.1341.87 (1.44–2.43)<0.001
Sex-0.3580.1830.70 (0.49–1.00)0.050
Age0.0060.0071.01 (0.99–1.02)0.369
Drinking (yes vs. no)0.0280.1521.03 (0.76–1.39)0.855
Smoking (yes vs. no)-0.2890.2620.75 (0.45–1.25)0.269
Obesity (vs. normal BMI)0.3340.2051.40 (0.94–2.09)0.102
Overweight (vs. normal BMI)0.3120.1251.37 (1.07–1.75)0.013
Underweight (vs. normal BMI)0.1590.2611.17 (0.70–1.96)0.543
Night sleep duration ≥6 h (vs. <6 h)-0.4820.1180.62 (0.49–0.78)<0.001
ADL disability (yes vs. no)0.8950.3452.45 (1.25–4.81)0.009
IADL disability (yes vs. no)0.2450.2421.28 (0.80–2.05)0.311
Depression score ≥10 (vs. <10)1.2110.1183.36 (2.66–4.23)<0.001
Cognition score-0.0250.0290.98 (0.92–1.03)0.389

Table 3: Multivariable logistic regression model without functional limitation score as the mediator. Results of the multivariable logistic regression analysis examining the association between recurrent falls and knee osteoarthritis without including functional limitations as a mediator. The dependent variable was knee osteoarthritis. Abbreviations; OR = odds ratio; CI = confidence interval; ADL = activities of daily living; IADL = instrumental activities of daily living.

VariableβSEOR (95% CI)p value
Recurrent falls (yes vs. no)0.5320.1381.70 (1.30–2.23)<0.001
Functional limitation score0.2290.0311.26 (1.18–1.34)<0.001
Sex-0.3570.1860.70 (0.49–1.01)0.056
Age0.0020.0071.00 (0.99–1.02)0.777
Drinking (yes vs. no)0.0400.1551.04 (0.77–1.41)0.794
Smoking (yes vs. no)-0.3330.2670.72 (0.42–1.21)0.213
Obesity (vs. normal BMI)0.2640.2101.30 (0.86–1.96)0.209
Overweight (vs. normal BMI)0.3130.1281.37 (1.07–1.76)0.014
Underweight (vs. normal BMI)0.1640.2671.18 (0.70–1.99)0.539
Night sleep duration ≥6 h (vs. <6 h)-0.4660.1210.63 (0.50–0.80)<0.001
ADL disability (yes vs. no)-0.0520.3870.95 (0.44–2.03)0.892
IADL disability (yes vs. no)-1.2190.3300.30 (0.15–0.56)<0.001
Depression score ≥10 (vs. <10)1.0600.1212.89 (2.27–3.66)<0.001
Cognition score-0.0240.0300.98 (0.92–1.04)0.421

Table 4: Multivariable logistic regression model including functional limitation score as the mediator. Results of the multivariable logistic regression analysis assessing the association between recurrent falls and knee osteoarthritis after adjusting for functional limitation score as a mediator. The dependent variable was knee osteoarthritis. Abbreviations; OR = odds ratio; CI = confidence interval; ADL = activities of daily living; IADL = instrumental activities of daily living.

EffectEstimate95% CIp value
Indirect effect through functional limitations0.0140.006–0.023<0.001
Direct effect0.0790.037–0.123<0.001
Total effect0.0930.050–0.138<0.001
Proportion mediated14.92%6.72–30.39%<0.001

Table 5: Bootstrap mediation analysis of the pathway from recurrent falls to knee osteoarthritis through functional limitations. Bootstrap mediation analysis quantifying the indirect effect of recurrent falls on knee osteoarthritis through functional limitations. Bootstrap mediation analysis was performed with 5,000 simulations. Abbreviations; CI = confidence interval.

Discussion

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This study examined the mediating role of functional limitations in the association between recurrent falls and knee osteoarthritis among middle-aged and older Chinese adults. The results showed that recurrent falls were associated with knee osteoarthritis and that functional limitations partially mediated this association. These findings indicate that functional decline is not only a consequence accompanying falls or knee symptoms, but also an important intermediate state linking fall history with knee osteoarthritis-related burden.

The mediation pattern observed in this study can be interpreted from the perspective of functional deterioration associated with recurrent falls. Falls are often accompanied by a sequence of physical and behavioral changes, including pain, soft-tissue injury, reduced postural confidence, fear of falling, and avoidance of movement40,41,42. These changes are associated with reduced walking exposure and daily activity participation, lower-limb deconditioning, poorer balance control, and impaired performance in activities of daily living43. In this process, functional limitations are not simply an outcome of aging, but a measurable expression of reduced musculoskeletal reserve after repeated fall-related stress.

Functional limitations provide a clinically relevant explanation for the association between recurrent falls and knee osteoarthritis through altered movement and loading patterns. When older adults experience functional decline, they often reduce knee flexion during gait, shorten step length, slow walking speed, and rely more heavily on compensatory hip, trunk, or contralateral limb strategies44. These adaptations may reduce immediate discomfort but can redistribute mechanical load across the knee joint and increase stress on cartilage, meniscus, subchondral bone, and periarticular soft tissues. At the same time, reduced activity accelerates quadriceps weakness and decreases dynamic knee stabilization, further increasing joint loading during standing, walking, and stair climbing45,46. Therefore, the mediating role of functional limitations should be interpreted as a clinically meaningful association pattern in which recurrent falls are linked to impaired mobility, and impaired mobility is linked to knee osteoarthritis-related symptoms and disability. This pathway also helps integrate the concepts of primary and secondary knee osteoarthritis. Primary knee osteoarthritis is related to aging, metabolic changes, low-grade inflammation, and long-term biomechanical stress, whereas secondary knee osteoarthritis is more closely related to trauma, joint instability, and abnormal loading47.

Recurrent falls are particularly relevant to the secondary or post-traumatic component because fall-related joint injury, pain-related gait changes, and loss of stability are closely associated with abnormal joint loading26,27. Functional limitations then provide the bridge between these injuries and daily mechanical exposure: the individual walks less, walks differently, and bears load less efficiently. This functional pattern can aggravate the interaction among pain, inactivity, muscle weakness, and knee symptoms.

From a clinical and public health perspective, these findings suggest that fall history and functional status should be assessed together in middle-aged and older adults with knee osteoarthritis or knee symptoms. Fall prevention should not be viewed only as a strategy to prevent fractures or acute injuries, but also as part of broader musculoskeletal health management. Interventions such as balance training, lower-limb strengthening, gait correction, functional rehabilitation, home environment modification, and community-based fall-risk screening may help interrupt the cycle of falls, functional decline, and knee-related disability48,49. The emphasis should be placed on maintaining safe mobility and preserving lower-limb function rather than only treating knee pain after symptoms become severe.

This study has several limitations and also provides directions for future research. First, recurrent falls, functional limitations, and knee osteoarthritis were all measured in the CHARLS 2015 survey wave. Therefore, the mediation results should be interpreted from the perspective of statistical association and mediation pattern rather than as direct evidence of temporal ordering or causality. Bidirectional associations should also be considered, because knee osteoarthritis-related pain and mobility impairment can influence both fall risk and functional status. Future studies should use repeated CHARLS waves or prospective cohort designs to further clarify the temporal sequence among recurrent falls, functional limitations, and knee osteoarthritis. Second, knee osteoarthritis was operationalized using knee pain location rather than radiographic assessment or physician diagnosis; this approach can introduce outcome misclassification because knee pain has multiple etiologies. Future research should incorporate radiographic evaluation, clinical diagnosis, or standardized knee osteoarthritis criteria to improve outcome classification50,51.

Third, recurrent falls and functional limitations were based on participant reports and are subject to recall and reporting bias. Future studies should include objective functional assessments, gait analysis, balance testing, fall records, or wearable-device-based monitoring to strengthen measurement accuracy. Fourth, residual confounding remains despite adjustment for major covariates, as factors such as physical activity, previous knee injury, medication use, comorbidity burden, pain severity, and environmental fall risks were not fully captured in the current analysis. Future analyses should include more comprehensive clinical, behavioral, and environmental variables. Finally, the use of bootstrap mediation analysis strengthened the estimation of the indirect effect by providing confidence intervals that do not rely on the assumption of normality. Nevertheless, the complex sampling and clustered structure of CHARLS data were not fully modeled. Future work should consider survey-weighted models, multilevel mediation approaches, and sensitivity analyses to further evaluate the robustness of the observed statistical mediation pattern.

Functional limitations were statistically associated with and partially mediated the relationship between recurrent falls and knee osteoarthritis among middle-aged and older Chinese adults. These findings indicate that functional limitations are an important statistical mediator in the association between recurrent falls and knee osteoarthritis. Integrating fall-risk assessment with functional-status evaluation should be considered in knee osteoarthritis-related health management for middle-aged and older adults. Longitudinal studies are needed to verify the temporal sequence and causal relationships among recurrent falls, functional limitations, and knee osteoarthritis.

Disclosures

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The authors report no conflicts of interest in this work.

Acknowledgements

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The authors thank the China Health and Retirement Longitudinal Study (CHARLS) team and all participants for providing the publicly available data used in this study.

Funding:
This work was supported by the 2025 General Program of Sichuan Administration of Traditional Chinese Medicine, Project No. 25MSZX135; the 2025 General Program of Chengdu Municipal Health Commission, Project No. 2025305; the 2025 Xinglin Scholar Independent Exploration Special Project of Chengdu University of Traditional Chinese Medicine, Project No. 330026199; and the Henan Students’ Innovation Training Program, Project No. 202510471007.

Materials

List of materials used in this article
NameCompanyCatalog NumberComments
China Health and Retirement Longitudinal Study 2015 survey dataChina Health and Retirement Longitudinal Study, Peking UniversityNot applicablePublicly available survey dataset used for the secondary analysis. Registered researchers can access the data through the CHARLS official website.
Dplyr R PackageCRANVersion 1.1.4Used for data cleaning, filtering, recoding, and variable construction.
Ggplot2 R PackageCRANVersion 3.4.4Used for visualization and figure preparation.
Mediation R PackageCRANVersion 4.5.1Used to perform bootstrap mediation analysis based on a linear mediator model and logistic outcome model.
Psych R PackageCRANVersion 2.5.6Used for descriptive statistics and scale-related data handling.
R softwareR Foundation for Statistical ComputingVersion 4.4.1Used for data processing, variable construction, statistical analysis, regression modeling, mediation analysis, and figure/table generation.
Tableone R PackageCRANVersion 0.13.2Used to summarize baseline characteristics of the study population.
Tidyverse R PackageCRANVersion 2.0.0Used for data organization and data management.

References

$$\rightleftharpoonup{xx}$$ $$\longleftharp{xx}$$, $$\longrightharp{xx}$$,
  1. Li, Z. M., Li, M. Improvement in orthopedic outcome score and reduction in IL-1β, CXCL13, and TNF-α in synovial fluid of osteoarthritis patients following arthroscopic knee surgery. Genet. Mol. Res. 16 (3), gmr16039487(2017).
  2. Shi, X., et al. A comparison of the effects of electroacupuncture vs transcutaneous electrical nerve stimulation for pain control in knee osteoarthritis: A protocol for network meta-analysis of randomized controlled trials. Medicine. 98 (28), e16265(2019).
  3. Zeng, C. Y., Zhang, Z. R., Tang, Z. M., Hua, F. Z. Benefits and mechanisms of exercise training for knee osteoarthritis. Front. Physiol. 12, 794062(2021).
  4. Sadatsuki, R., et al. Bone marrow lesion is associated with disability for activities of daily living in patients with early stage knee osteoarthritis. J. Bone Miner. Metab. 37 (3), 529-536 (2019).
  5. O'Connell, M., Farrokhi, S., Fitzgerald, G. K. The role of knee joint moments and knee impairments on self-reported knee pain during gait in patients with knee osteoarthritis. Clin. Biomech. 31, 40-46 (2016).
  6. Issa, S. N., Sharma, L. Epidemiology of osteoarthritis: an update. Curr. Rheumatol. Rep. 8 (1), 7-15 (2006).
  7. Sun, X., et al. Osteoarthritis in the middle-aged and elderly in China: prevalence and influencing factors. Int. J. Environ. Res. Public Health. 16 (23), 4701(2019).
  8. Singh, A. K., Kalaivani, M., Krishnan, A., Aggarwal, P. K., Gupta, S. K. Prevalence of osteoarthritis of knee among elderly persons in urban slums using American College of Rheumatology criteria. J. Clin. Diagn. Res. 8 (9), JC09-JC11 (2014).
  9. Wood, A. M., Brock, T. M., Heil, K., Holmes, R., Weusten, A. A review of the management of hip and knee osteoarthritis. Int. J. Chronic Dis. 2013, 845015(2013).
  10. Tangtrakulwanich, B., Chongsuvivatwong, V., Geater, A. F. Habitual floor activities increase risk of knee osteoarthritis. Clin. Orthop. Relat. Res. 454, 147-154 (2007).
  11. Castro-Dominguez, F., et al. Literature review to understand the burden and current non-surgical management of moderate-severe pain associated with knee osteoarthritis. Rheumatol. Ther. 11 (6), 1457-1499 (2024).
  12. Leardini, G., et al. Direct and indirect costs of osteoarthritis of the knee. Clin. Exp. Rheumatol. 22 (6), 699-706 (2004).
  13. Loza, E. Economic burden of knee and hip osteoarthritis in Spain. Arthritis Rheum. 61 (2), 158-165 (2009).
  14. Summanen, M., Ukkola-Vuoti, L., Kurki, S., Tuominen, S., Madanat, R. The burden of hip and knee osteoarthritis in Finnish occupational healthcare. BMC Musculoskelet. Disord. 22 (1), 501(2021).
  15. Neyens, J. C., Dijcks, B. P., de Kinkelder, A., Graafmans, W. C., Schols, J. M. CBO guidelines to prevent accidental falls in the elderly: how can it be used in the institutionalized elderly? Tijdschr. Gerontol. Geriatr. 36 (4), 155-160 (2005).
  16. Seo, Y., Kim, K., Kim, J. S. Trends of nursing research on accidental falls: a topic modeling analysis. Int. J. Environ. Res. Public Health. 18 (8), 3963(2021).
  17. Heinimann, N. B., Kressig, R. W. Accidental falls in the elderly. Praxis. 103 (13), 767-773 (2014).
  18. Iglesias, C. P., Manca, A., Torgerson, D. J. The health-related quality of life and cost implications of falls in elderly women. Osteoporos. Int. 20 (6), 869-878 (2009).
  19. Dionyssiotis, Y., Dontas, I. A., Economopoulos, D., Lyritis, G. P. Rehabilitation after falls and fractures. J. Musculoskelet. Neuronal Interact. 8 (3), 244-250 (2008).
  20. Ribeiro, A. P., de Souza, E. R., Atie, S., de Souza, A. C., Schilithz, A. O. The influence of falls on the quality of life of the aged. Cien. Saude Colet. 13 (4), 1265-1273 (2008).
  21. Kakara, R., Bergen, G., Burns, E., Stevens, M. Nonfatal and fatal falls among adults aged ≥65 years—United States, 2020–2021. MMWR Morb. Mortal. Wkly Rep. 72 (35), 938-943 (2023).
  22. Reinoso, H., McCaffrey, R. G., Taylor, D. W. M. Mitigating fall risk: a community fall reduction program. Geriatr. Nurs. 39 (2), 199-203 (2018).
  23. Phelan, E. A., Ritchey, K. Fall prevention in community-dwelling older adults. Ann. Intern. Med. 169 (11), ITC81-ITC96 (2018).
  24. Bodrud-Doza, M., et al. Psychosocial and socio-economic crisis in Bangladesh due to the COVID-19 pandemic: a perception-based assessment. Front. Public Health. 8, 341(2020).
  25. McDaid, D., et al. Health protection in times of economic crisis: challenges and opportunities for Europe. J. Public Health Policy. 34 (4), 489-501 (2013).
  26. Belluzzi, E., et al. Conditioned media from human osteoarthritic synovium induces inflammation in a synoviocyte cell line. Connect. Tissue Res. 60 (2), 136-145 (2019).
  27. Biz, C., et al. Challenging surgical treatment of displaced articular tibial plateau fractures: do early knee radiographic features have a predictive value of the mid-term clinical functional outcomes? Orthop. Surg. 11 (6), 1149-1162 (2019).
  28. Chen, L., Zhang, Z., Liu, X. Role and mechanism of mechanical load in the homeostasis of the subchondral bone in knee osteoarthritis: a comprehensive review. J. Inflamm. Res. 17, 9359-9378 (2024).
  29. Ozeki, N., Koga, H., Sekiya, I. Degenerative meniscus in knee osteoarthritis: from pathology to treatment. Life. 12 (4), 603(2022).
  30. Ni, X., et al. Physical therapy options for knee osteoarthritis: a review. Medicine. 103 (30), e38415(2024).
  31. Pinheiro, M. M., et al. Risk factors for recurrent falls among Brazilian women and men: the Brazilian Osteoporosis Study (BRAZOS). Cad. Saude Publica. 26 (1), 89-96 (2010).
  32. Ganz, D. A., et al. Effect of the STRIDE fall injury prevention intervention on falls, fall injuries, and health-related quality of life. J. Am. Geriatr. Soc. 70 (11), 3221-3229 (2022).
  33. Zhao, Y., Hu, Y., Smith, J. P., Strauss, J., Yang, G. Cohort profile: the China Health and Retirement Longitudinal Study (CHARLS). Int. J. Epidemiol. 43 (1), 61-68 (2014).
  34. Lin, P., et al. Risk of fall in patients with chronic kidney disease: results from the China Health and Retirement Longitudinal Study (CHARLS). BMC Public Health. 24 (1), 499(2024).
  35. Wang, L., Lu, H., Chen, H., Jin, S., Wang, M., et al. Development of a model for predicting the 4-year risk of symptomatic knee osteoarthritis in China: a longitudinal cohort study. Arthritis Res. Ther. 23 (1), 65(2021).
  36. Katz, S., Ford, A. B., Moskowitz, R. W., Jackson, B. A., Jaffe, M. W. Studies of illness in the aged: the index of ADL, a standardized measure of biological and psychosocial function. JAMA. 185, 914-919 (1963).
  37. Chen, H., Mui, A. C. Factorial validity of the Center for Epidemiologic Studies Depression Scale short form in older population in China. Int. Psychogeriatr. 26 (1), 49-57 (2014).
  38. Yu, J., Feng, Q., Yu, J., Zeng, Y., Feng, L. Late-life cognitive trajectories and their associated lifestyle factors. J. Alzheimers Dis. 73 (4), 1555-1563 (2020).
  39. Jiang, Y., Fu, J., Zhou, C., Yue, X., Liu, Y. Associations between productive engagement and intrinsic capacity and their longitudinal effects on subjective well-being among older adults: a cross-lagged panel mediation analysis. J. Nutr. Health Aging. 30 (7), 100867(2026).
  40. Yiu, J., Miller, W. C., Eng, J. J., Liu, Y. Longitudinal analysis of balance confidence in individuals with stroke using a multilevel model for change. Neurorehabil. Neural Repair. 26 (8), 999-1006 (2012).
  41. Noeske, K. E., et al. Walking self-confidence and lower levels of anxiety are associated with meeting recommended levels of physical activity after hip fracture: a cross-sectional study. Disabil. Rehabil. 47 (1), 135-141 (2025).
  42. Visschedijk, J. H., Caljouw, M. A., van Balen, R., Hertogh, C. M., Achterberg, W. P. Fear of falling after hip fracture in vulnerable older persons rehabilitating in a skilled nursing facility. J. Rehabil. Med. 46 (3), 258-263 (2014).
  43. Yosef, T., Pasco, J. A., Tembo, M. C., Holloway-Kew, K. L. Hip abductor strength predicts injurious falls and mediates the balance confidence-falls relationship: a competing risk model. J. Cachexia Sarcopenia Muscle. 17 (2), e70280(2026).
  44. Anan, M., Tokuda, K., Tanimoto, K., Sawada, T. The relationship between knee flexion excursion and mechanical stress during gait in medial knee osteoarthritis. Clin. Biomech. 112, 106180(2024).
  45. Buford, T. W., et al. Kaatsu training to enhance physical function of older adults with knee osteoarthritis: design of a randomized controlled trial. Contemp. Clin. Trials. 43, 217-222 (2015).
  46. Raghava Neelapala, Y. V., Bhagat, M., Shah, P. Hip muscle strengthening for knee osteoarthritis: a systematic review of literature. J. Geriatr. Phys. Ther. 43 (2), 89-98 (2020).
  47. Syrikas, I., Engbäck, C., Tsikandylakis, G., Karikis, I., Desai, N. Increased complications rates and inferior patient-reported outcomes following total knee arthroplasty due to post-traumatic osteoarthritis with previous fracture treatment: a systematic review. Knee Surg. Sports Traumatol. Arthrosc. 31 (10), 4124-4141 (2023).
  48. de Souza, T. S., Pereira, D. B., Hagihara, R. J., Fuzinato, C. T., Ribeiro, A. P. Effect of rehabilitation program for muscle strength, balance, and gait retraining with visual feedback in older women with and without knee osteoarthritis: a clinical trial. J. Pers. Med. 15 (12), 631(2025).
  49. Gonzalez Aroca, J., Vergara Merino, L., Meza, N., Gonzalez, C., Ramirez Araya, P., et al. Interventions for improving adherence to exercise-based treatments in people with knee osteoarthritis. Cochrane Database Syst. Rev. 2025 (7), CD016088(2025).
  50. Seeley, M. K., et al. A review of the relationships between knee pain and movement neuromechanics. J. Sport Rehabil. 31 (6), 684-693 (2021).
  51. Seeley, M. K., Park, J., King, D., Hopkins, J. T. A novel experimental knee-pain model affects perceived pain and movement biomechanics. J. Athl. Train. 48 (3), 337-345 (2013).

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Knee OsteoarthritisRecurrent FallsFunctional LimitationsMediation AnalysisLogistic RegressionSpearman CorrelationFall Risk AssessmentFunctional Status EvaluationMiddle Aged AdultsCHARLS Survey

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