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Associations of chronic disease status and the risk of new-onset hip or femoral fractures in older population
⁎Corresponding author: Peng Wang. wangpeng19910318@sina.com
⁎⁎Corresponding author: Hai-Feng Pan. panhaifeng@ahmu.edu.cn
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Received: ,
Accepted: ,
This article was originally published by Reed Elsevier India Pvt. Ltd. and was migrated to Scientific Scholar after the change of Publisher.
Abstract
Abstract
Chronic disease status (CDS) is common across the elderly, but the association between CDS and risks of hip or femoral fracture in this population is unknown.
This prospective cohort study aimed to investigate the associations between CDS and risks of hip or femoral fractures in the elderly.
The longitudinal cohort data utilized in this study were obtained from waves 1 to 9 of the European Survey of Health, Ageing, and Retirement (SHARE), ranging from April 2004 to April 2024. A total of 12 kinds of chronic diseases were identified and then allocated into different multimorbidity patterns, including single disease, somatic multimorbidity (SMM), cardiometabolic multimorbidity (CMM), and neuropsychiatric multimorbidity (NPM). Sub-distribution models, cause-specific hazard models, and subgroup analysis were used to analyze the association between CDS and the risk of hip or femoral fracture.
A total of 24,051 eligible participants were included, of whom 913 (3.8 %) had reported an occurrence of hip or femoral fracture during follow-up. Adjusted for demographic variables in sub-distribution models, participants with hypertension (sub-distribution hazard ratio [sHR] = 1.39, 95 %CI: 1.15, 1.68) and osteoporosis (sHR = 1.53, 95 %CI: 1.18, 1.98) were shown to be associated with a higher risk of hip or femoral fracture, considering the competing effect of all-cause death; these findings remained robust in sensitivity analyses. Additionally, sociodemographic factors and lifestyle behaviors such as gender, region, education, occupation, household, alcohol consumption, and smoking modified the association between CDS and hip or femoral fracture.
Hypertension and osteoporosis are associated with an increased risk of hip or femoral fracture in the elderly, region, education, and occupation are important factors contributing to the risk of hip or femoral fracture. Advancing disease management and integrating comprehensive care strategies would be helpful for the early prevention of hip or femoral fractures in this population.
Abstract
Highlights
Clinical Significance.1.This population-based cohort study is the first preliminary investigation of the relationship between chronic diseases, multimorbidity and hip or femoral fracture incidence in older adults.2.The use of sub-distributions models and cause-specific hazard models could ensure the appreciation of our approach, with a series of sensitivity analyses to confirm the robustness of our findings.3.Our study investigates the potential influence of social determinants of health (SDoH) and lifestyle behaviors in aiding policymakers to target intervention strategies for stroke risks associated with chronic diseases and multimorbidity.4.The extensive sample spanning various European nations and the robust population representation in SHARE provide a basis for gathering thorough and dependable data.
Keywords
Hip fracture
Chronic disease status
Cohort study
Disease risk
1 Introduction
Hip or femoral fracture is a prevalent condition affecting the femur's neck and trochanteric areas.1 It is a common and severe type of injury among the elderly population, often resulting in mortality, disability, functional impairment, and a multitude of complications.2 Additionally, it necessitates prolonged bed rest and treatment periods. In the United States alone, over 300,000 hip fractures occur annually, with an estimated annual treatment cost per patient of $40,000.3 The one-year mortality rate following a hip or femoral fracture has been reported to range between 14 % and 36 %.4 The mortality and morbidity attributable to hip or femoral fracture significantly increase with aging,5 and the prevalence is projected to reach 6.3 million by 2050.6 As the population ages, life expectancy increases, and living standards continue to improve hip or femoral fractures have emerged as a critical public health challenge.
Chronic diseases are characterized by complex etiology, prolonged duration, persistent symptoms, and poor prognosis. In 2023, they were responsible for 41 million deaths, accounting for 74 % of total global mortality, with approximately 80 % resulting from primary chronic conditions such as cardiovascular diseases, cancer, chronic respiratory diseases, and diabetes.7 It has been established that chronic disease status (CDS) is closely linked to various illnesses, including kidney function,8 depression,9 cancer,10 and Alzheimer's disease.11 As the number of chronic diseases increases, patients experience higher rates of healthcare utilization and increased risk of mortality.12
With the ageing population and rising prevalence of chronic diseases, chronic disease states have become an essential area of research. Emerging evidence suggests a possible link between various chronic disease states and the occurrence and adverse outcomes of hip fracture,13 where previous studies demonstrated increased susceptibility to hip or femoral fracture in middle-aged and elderly populations with specific chronic illnesses such as depression14 and osteoporosis.15 These associations indicate that certain diseases may impact bone health. However, research on other chronic diseases, such as hypertension, diabetes, chronic lung disease, and multimorbidity, has not yet yielded definitive conclusions. Whether specific chronic conditions increase the risk of hip or femoral fractures and whether this relationship varies across different populations remain uncertain.
Given the substantial burden of hip or femoral fracture, further research into the relationship between CDS and the incidence of hip or femoral fracture is of significant practical importance, with profound implications for bone health management in older adults. In this study, we conducted a prospective analysis using data from the Survey of Health, Ageing, and Retirement in Europe (SHARE) to investigate the longitudinal relationship between CDS and hip or femoral fracture risk among European older adults.
2 Methods
2.1 Study population and ethics
In this study, we utilized prospective cohort data from nine waves of the SHARE study. Information was collected between 2004 and 2024, with every wave taking approximately 2 years to complete. SHARE is a longitudinal population study database with multidisciplinary information on health, social networks, and the socio-economic status of approximately 140,000 adults aged 50 and above in 27 European countries and Israel. The SHARE obtained ethical approval from the Ethics Committee of the Max Planck Society and the respective committees in participating countries. All participants provided written informed consent before enrollment. In 2004, a total of 30,419 participants aged over 45 years completed the baseline survey after excluding those missing (n = 6,368) and previous hip or femoral fracture cases (n = 1,123). Ultimately, 24,051 eligible participants (10,799 males and 13,252 females) were included in our study (Supplementary Fig. 1).
2.2 The definitions of CDS
In this study, we divided CDS into individual diseases and multimorbidity. In the SHARE questionnaire, participants were asked, “Has a doctor ever told you that you had any of the conditions: hypertension, diabetes, dyslipidemia, heart disease, lung disease, digestive disease, cataract, arthritis, osteoporosis, asthma, stroke, cancer, depression, and dementia?”. Depression and dementia were categorized under Neuropsychiatric conditions, while other chronic illnesses were grouped as Somatic diseases. Additionally, conditions such as high blood pressure, diabetes, heart attack, and dyslipidemia were classified as Cardiometabolic disorders.
Multimorbidity refers to having two or more chronic diseases at the same time. Somatic multimorbidity (SMM) includes the co-existence of two or more somatic diseases. Cardiometabolic multimorbidity (CMM) involves the co-existence of two or more cardiometabolic diseases. Neuropsychiatric multimorbidity (NPM) involves two conditions: depression and dementia.
2.3 Ascertainment of outcomes
Participants' hip or femoral fracture diagnoses were ascertained based on their self-reported information during subsequent survey follow-ups. During each assessment, respondents were asked, “Have you been diagnosed with a hip fracture or femoral fracture by a doctor?”.
Death from any cause was confirmed by proxy respondents (e.g., a spouse, other family member, or neighbor) during follow-up.
2.4 Covariates
All exposure and covariate data were collected at each wave assessment (touch-screen questionnaire and personal interview). From the baseline waves, the study extracted the following covariates: age, gender, education, occupation, household income, marital status, current smoking, current drinking, irregular physical activity, BMI, frailty and loneliness, use of psychotropic or sedative medications, and use of other medications, etc.
The ages of participants were recorded based on self-reported age during interviews at wave 1. This study identified six social determinants of health (SDoH): gender, geographical region, educational attainment, occupation, household income, and marital status. Educational levels were categorized based on the highest completed degree: below high school, high school, and college or higher. Occupation status included employed or self-employed, retired, and other categories. According to the annual household income, household income was classified into three the lower, middle, and upper levels. Marital status included being married or cohabiting and being single. In addition, lifestyle behaviors were also analyzed for their impact on fracture. Smoking and alcohol consumption were determined based on self-reported current smoking and alcohol consumption. Irregular physical activity was defined as moderate and vigorous exercise or training less than once a week. Body mass index (BMI) (underweight: < 18.5 kg/m2, normal: 18.5–24.5 kg/m2, overweight: 25.0–29.9 kg/m2, obesity: ≥ 30.0 kg/m2).
Participants in the SHARE survey were queried about their concerns regarding four aspects of daily life vulnerability: falling, fear of falling, dizziness, and fatigue. At the same time, those with any condition of vulnerability were classified as vulnerable. The modified version of the Revised UCLA loneliness scale was used to evaluate the degree of loneliness that included "forgotten" "isolated from others" and "lack of companionship",16 with choices of "almost never or never" (set to 1), "sometimes" (set to 2), and "often" (set to 3). The loneliness score was 3–9 points, the scoring six points and the above participants were classified as lonely.17 Besides, medication taken simultaneously for sleep issues or psychiatric conditions was documented as psychotropic or sedative medication usage. Medications for heart diseases, diabetes, hyperlipidemia, arthritis and osteoporosis, gastrointestinal disorders, and pulmonary diseases were recorded.
2.5 Statistical analysis
Baseline characteristics were reported with categorical variables as frequencies and percentages, while continuous data were expressed using mean values and their corresponding standard deviations (SD). Missing portions of included covariates were represented by "missing". Mann-Whitney U test was performed for continuous variables, while the Chi-square test was conducted to investigate the differences between categorical variables.
We calculated the incidence density of hip or femoral fracture and all-cause mortality per 100,000 person-years for participants. Sub-distribution and cause-specific hazard models were used to examine the associations between chronic disease states at baseline (wave 1) and the incidence of hip or femoral fracture from 2006 to 2024 (wave 2 to wave 9), with all-cause death as the competing event. Competing risks are events that, when they happen, alter the risk linked to the main event of interest. In our study, the primary outcome was defined as the incidence of hip or femoral fracture; participants who died from any cause would no longer be at risk of hip or femoral fracture.18 The proportional hazards assumption (PHA) in each Cox regression model was assessed using scaled Schoenfeld residuals. Age, gender, country of residence, education level, occupational status, household income, marital status, smoking, alcohol consumption, irregular physical activity, BMI, frailty, feelings of loneliness, use of psychotropic or sedative medications, and other drug use were included as adjustment variables in all models.
To ensure the reliability of the results, we conducted two sensitivity analyses: First, to mitigate the influence of potential reverse-causality bias and consider a latency period. We excluded participants with a diagnosis of hip or femoral fracture between 2004 and 2012. Second, participants' geographical distribution was considered to enhance the generalizability of findings from the analytic sample to the broader population. In addition, the subgroup analyses of SDoH and lifestyle behaviors were conducted to further explore multiplication interactions between CDS and the incidence of hip or femoral fracture, with the adjustments of covariates.
The STATA 17 software was utilized to carry out the data analysis procedures. We calculated the hazard ratio in the multivariable analysis with a 95 % confidence interval (CI) of the sub-distribution hazard ratio (sHR) and cause-specific hazard ratio (cHR). A P value < 0.05 was considered a statistical significance.
3 Results
3.1 Baseline characteristics of study participants
A total of 30,419 participants were enrolled in Wave 1. Between 2004 and 2024, 182 participants were lost to follow-up. Additionally, 5,036 participants with no history of chronic disease, 17 participants younger than 45 years of age, and 1,123 participants who had experienced a hip or femoral fracture at baseline were excluded from the study. Consequently, 24,051 participants were included in the final analysis (Fig. S1). Over approximately two decades of follow-up, the baseline cohort comprised 24,051 participants with a mean age of 64.1 years (SD = 10.26), of whom 44.90 % were male. During the 21-year follow-up period, 913 participants reported hip or femoral fractures and 5,139 participants died (Fig. 1 & Table 1). Baseline analysis indicated that participants with multimorbidity, specifically SMM and CMM, exhibited a significantly higher risk of hip or femoral fracture incidence (all P values < 0.05).
| Characteristics | No new-onset Hip Fracture (N = 23138) | New-onset Hip Fracture (N = 913) | P value |
| Age | 63.9(45.0–103.0) | 69.2(45.0–93.0) | <0.001 |
| Gender | <0.001 | ||
| Male | 10489(44.90) | 320(34.52) | |
| Female | 12664(54.21) | 605(65.26) | |
| Education | 0.001 | ||
| Less than high school | 9527(40.78) | 323(34.84) | |
| High school | 6578(28.16) | 289(31.18) | |
| College or above | 7256(31.06) | 315(33.98) | |
| Occupation | <0.001 | ||
| Employed or self-employed | 7013(30.02) | 105(11.33) | |
| Retired | 10649(45.58) | 578(62.35) | |
| Others | 5206(22.29) | 226(24.38) | |
| Missing | 493(2.11) | 18(1.94) | |
| Household income | <0.001 | ||
| Bottom tertile | 7206(30.85) | 338(36.46) | |
| Middle tertile | 7045(30.16) | 288(31.07) | |
| Top tertile | 7084(30.32) | 211(22.76) | |
| Missing | 2000(8.64) | 90(9.71) | |
| Marital status | <0.001 | ||
| Married/cohabiting | 17127(73.31) | 594(64.08) | |
| Single | 6231(26.67) | 333(27.1) | |
| Missing | 3(0.01) | 0(0.00) | |
| Current drinking | <0.001 | ||
| Yes | 15993(68.46) | 561(60.52) | |
| No | 7358(31.50) | 365(39.37) | |
| Missing | 10(0.04) | 1(0.11) | |
| Current smoking | <0.001 | ||
| Yes | 4488(19.21) | 129(13.92) | |
| No | 18865(80.75) | 797(85.98) | |
| Missing | 8(0.03) | 1(0.11) | |
| Irregular physical activity | <0.001 | ||
| Yes | 20068(85.90) | 709(76.48) | |
| No | 3289(14.08) | 217(23.41) | |
| Missing | 4(0.02) | 1(0.11) | |
| Frailty | <0.001 | ||
| Yes | 8861(37.93) | 485(46.1) | |
| No | 14268(61.08) | 441(47.57) | |
| Missing | 232(0.3) | 0(0.11) | |
| Loneliness | 0.047 | ||
| Yes | 1913(8.19) | 97(10.46) | |
| No | 14148(60.56) | 545(58.79) | |
| Missing | 7300(31.25) | 285(30.74) | |
| History of cancer | 0.103 | ||
| Yes | 1220(5.22) | 58(6.26) | |
| No | 22009(94.21) | 860(92.77) | |
| Missing | 132(0.57) | 9(0.97) | |
| Use of psychotropic or sedative medicines | <0.001 | ||
| Yes | 2699(11.55) | 741(79.94) | |
| No | 20511(87.80) | 175(18.88) | |
| Missing | 151(0.65) | 11(1.19) | |
| Use of other medicines | <0.001 | ||
| Yes | 15546(66.55) | 754(81.34) | |
| No | 7654(32.76) | 162(17.48) | |
| Missing | 161(0.69) | 11(1.19) | |
| Multimorbidity | <0.001 | ||
| Yes | 11136(47.67) | 590(63.65) | |
| No | 12225(52.33) | 337(36.35) | |
| SMM | <0.001 | ||
| Yes | 7961(34.08) | 457(49.30) | |
| No | 15400(65.92) | 470(50.70) | |
| NPM | 0.207 | ||
| Yes | 128(0.55) | 8(0.86) | |
| No | 23233(99.45) | 919(99.14) | |
| CMM | <0.001 | ||
| Yes | 4652(19.91) | 258(27.83) | |
| No | 18709(80.09) | 669(72.17) |
3.2 Association of CDS with risk of hip or femoral fracture
Participants who had multimorbidity at baseline showed the highest incidences of hip or femoral fracture and all-cause mortality, followed by SMM and hypertension (Figs. 1 and 2). To investigate the impact of single diseases and multimorbidity on the incidence of hip or femoral fractures, we initially conducted a multivariate Cox regression analysis. The findings revealed that patients with hypertension (cHR = 1.36; 95 %CI: 1.13–1.65) and osteoporosis (cHR = 1.49, 95 %CI: 1.15–1.91) exhibited a significantly higher risk of experiencing hip or femoral fractures compared to those without these conditions (Fig. 3). After adjusting for competing events, the results from multivariate competing risk analyses remained consistent, demonstrating adjusted subdistribution hazard ratios of 1.39 (95 %CI: 1.15–1.68) for hypertension and 1.53 (95 %CI: 1.18–1.98) for osteoporosis (Fig. 4) (all P values < 0.05). The significant associations between hypertension and osteoporosis and the elevated risk of hip or femoral fractures were robust across all sensitivity analyses (Tables S1–S2).
3.3 SDoH and lifestyle behaviors subgroup analysis
We analyzed the interaction between SDoH and the incidence of hypertension, osteoporosis, and fracture. A significant interaction was revealed between living in Western Europe and hypertension (sHR = 1.76, 95 %CI: 1.33–2.33, P = 0.020), as evidenced by multivariable Cox regression analysis and competitive risk analysis. When analyzing medication use under the corresponding conditions, we found a significant interaction between having high blood pressure and not using medication and fracture in the competitive risk regression model (sHR = 1.50, 95 %CI: 1.01–2.23), although the overall interaction outcome was not significant (P = 0.201). Furthermore, the competitive risk regression model revealed a significant interaction between the educational level (university or higher) and retirement status of osteoporosis patients in Southern Europe (sHR = 1.76, 95 %CI: 1.33–2.33, P = 0.020). The subgroup analysis of lifestyle behaviors found no significant association between smoking, alcohol consumption, irregular exercise habits, and BMI, on the one hand, and hypertension or osteoporosis, on the other (Tables 2 and 3) (all P < 0.05).
| Hypertension | Osteoporosis | |
| Gender-stratified analysis | ||
| P for interaction | 0.205 | 0.871 |
| Men | ||
| sHR (95 % CI) | 1.26(0.98–1.63) | 1.38(0.68–2.79) |
| cHR (95 % CI) | 1.26(0.92–1.73) | 1.38(0.62–3.05) |
| Women | ||
| sHR (95 % CI) | 1.15(0.94–1.40) | 0.96(0.76–1.21) |
| cHR (95 % CI) | 1.15(0.89–1.47) | 0.96(0.70–1.32) |
| Region-stratified analysis | ||
| P for interaction | 0.020 | 0.974 |
| Northern Europe | ||
| sHR (95 % CI) | 0.84(0.62–1.13) | 0.62(0.33–1.15) |
| cHR (95 % CI) | 0.84(0.58–1.23) | 0.62(0.25–1.56) |
| Central Europe | ||
| sHR (95 % CI) | 1.11(0.81–1.53) | 1.39(0.91–2.13) |
| cHR (95 % CI) | 1.11(0.77–1.61) | 1.39(0.82–2.37) |
| Western Europe | ||
| sHR (95 % CI) | 1.76(1.33–2.33) | 0.89(0.63–1.27) |
| cHR (95 % CI) | 1.76(1.18–2.62) | 0.89(0.50–1.58) |
| Southern Europe (Israel) | ||
| sHR (95 % CI) | 1.32(1.03–1.69) | 0.99(0.72–1.38) |
| cHR (95 % CI) | 1.32(0.93–1.86) | 0.99(0.62–1.58) |
| Education-stratified analysis | ||
| P for interaction | 0.082 | 0.742 |
| Less than high school | ||
| sHR (95 % CI) | 1.10(0.84–1.43) | 1.16(0.79–1.69) |
| cHR (95 % CI) | 1.09(0.79–1.52) | 1.16(0.73–1.84) |
| High school | ||
| sHR (95 % CI) | 1.15(0.90–1.47) | 0.93(0.65–1.32) |
| cHR (95 % CI) | 1.15(0.82–1.61) | 0.93(0.57–1.51) |
| College or above | ||
| sHR (95 % CI) | 1.35(1.02–1.79) | 0.89(0.63–1.26) |
| cHR (95 % CI) | 1.35(0.94–1.95) | 0.89(0.54–1.49) |
| Occupation-stratified analysis | ||
| P for interaction | 0.120 | 0.645 |
| Employed or self-employed | ||
| sHR (95 % CI) | 1.16(0.94–1.44) | 1.08(0.80–1.46) |
| cHR (95 % CI) | 1.16(0.90–1.51) | 1.08(0.74–1.58) |
| Retired | ||
| sHR (95 % CI) | 0.99(0.62–1.59) | 2.07(1.09–3.91) |
| cHR (95 % CI) | 0.99(0.51–1.92) | 2.07(0.70–6.07) |
| Others | ||
| sHR (95 % CI) | 1.33(0.96–1.85) | 0.79(0.57–1.09) |
| cHR (95 % CI) | 1.33(0.86–2.06) | 0.79(0.47–1.31) |
| Household income-stratified analysis | ||
| P for interaction | 0.292 | 0.967 |
| Bottom tertile | ||
| sHR (95 % CI) | 1.31(1.02–1.67) | 0.95(0.73–1.23) |
| cHR (95 % CI) | 1.31(0.95–1.79) | 0.95(0.65–1.38) |
| Middle tertile | ||
| sHR (95 % CI) | 1.15(0.85–1.56) | 1.36(0.79–2.36) |
| cHR (95 % CI) | 1.15(0.82–1.61) | 1.36(0.73–2.52) |
| Top tertile | ||
| sHR (95 % CI) | 1.03(0.76–1.41) | 0.89(0.54–1.49) |
| cHR (95 % CI) | 1.03(0.68–1.56) | 0.89(0.45–1.76) |
| Marital status-stratified analysis | ||
| P for interaction | 0.101 | 0.970 |
| Married/cohabiting | ||
| sHR (95 % CI) | 1.12(0.90–1.40) | 1.01(0.70–1.45) |
| cHR (95 % CI) | 1.12(0.84–1.50) | 1.01(0.62–1.63) |
| Single | ||
| sHR (95 % CI) | 1.27(0.98–1.65) | 0.99(0.76–1.30) |
| cHR (95 % CI) | 1.27(0.92–1.74) | 0.99(0.68–1.44) |
| Use Hypertension drugs | Use Osteoporosis drugs | |
| P for interaction | 0.201 | 0.655 |
| Yes | ||
| sHR (95 % CI) | 1.15(0.96–1.38) | 0.81(0.57–1.15) |
| cHR (95 % CI) | 1.15(0.92–1.44) | 0.81(0.49–1.33) |
| No | ||
| sHR (95 % CI) | 1.50(1.01–2.23) | 1.10(0.85–1.42) |
| cHR (95 % CI) | 1.50(0.93–2.41) | 1.10(0.78–1.55) |
| Hypertension | Osteoporosis | |
| Smoking-stratified analysis | ||
| P for interaction | 0.086 | 0.917 |
| Yes | ||
| sHR (95 % CI) | 1.46(0.99–2.16) | 1.19(0.63–2.25) |
| cHR (95 % CI) | 1.46(0.84–2.54) | 1.19(0.52–2.76) |
| No | ||
| sHR (95 % CI) | 1.14(0.95–1.38) | 0.97(0.77–1.23) |
| cHR (95 % CI) | 1.14(0.91–1.45) | 0.97(0.71–1.34) |
| Alcohol consumption-stratified analysis | ||
| P for interaction | 0.160 | 0.859 |
| Yes | ||
| sHR (95 % CI) | 1.16(0.93–1.44) | 1.08(0.79–1.46) |
| cHR (95 % CI) | 1.16(0.89–1.51) | 1.08(0.73–1.58) |
| No | ||
| sHR (95 % CI) | 1.24(0.93–1.65) | 0.90(0.70–1.22) |
| cHR (95 % CI) | 1.24(0.85–1.80) | 0.90(0.57–1.41) |
| Irregular exercise habits-stratified analysis | ||
| P for interaction | 0.254 | 0.838 |
| Yes | ||
| sHR (95 % CI) | 1.10(0.91–1.32) | 1.07(0.83–1.37) |
| cHR (95 % CI) | 1.10(0.87–1.38) | 1.07(0.77–1.49) |
| No | ||
| sHR (95 % CI) | 1.81(1.22–2.68) | 0.76(0.48–1.20) |
| cHR (95 % CI) | 1.81(1.08–3.02) | 0.76(0.40–1.46) |
| BMI-stratified analysis | ||
| P for interaction | 0.113 | 0.853 |
| Underweight | ||
| sHR (95 % CI) | 1.72(1.16–2.55) | |
| cHR (95 % CI) | 1.72(0.40–7.41) | |
| Normal | ||
| sHR (95 % CI) | 1.17(0.91–1.52) | 0.95(0.68–1.32) |
| cHR (95 % CI) | 1.17(0.84–1.64) | 0.95(0.60–1.49) |
| Overweight | ||
| sHR (95 % CI) | 1.10(0.88–1.38) | 0.89(0.63–1.26) |
| cHR (95 % CI) | 1.10(0.82–1.48) | 0.89(0.56–1.42) |
| Obesity | ||
| sHR (95 % CI) | 1.38(0.96–1.98) | 1.30(0.87–1.94) |
| cHR (95 % CI) | 1.38(0.90–2.12) | 1.30(0.74–2.28) |
4 Discussion
In this prospective cohort study, we found that hypertension and osteoporosis increased the risk of hip or femoral fracture in older adults, and this risk persisted even after adjusting for competing risks of overall mortality. While the relationship between specific chronic diseases and hip or femoral fracture occurrence varies. In addition, hip or femoral fractures are associated with region, education, and occupation. Our findings, together with previous studies, have confirmed that certain chronic diseases play a significant role in the occurrence and development of fractures in elderly individuals. Hip fracture is one of the most common health consequences of osteoporosis in the elderly. Patients with osteoporosis have reduced bone mass and deterioration of bone structure, leading to a higher risk of secondary fracture in patients. Previous studies have shown that over 65 % of hip fracture in people aged 80 and above are attributed to osteoporosis.19 A study conducted in a hospital outpatient clinic on postmenopausal women over the age of 45 with osteoporosis showed that, in each age group, the fracture incidence rate for patients with osteoporosis was approximately twice that of those without fractures.20
In addition to osteoporosis, we also found that hypertension was associated with the risk of hip or femoral fracture. Accumulating evidence focused on the impact of ischemic heart disease and cerebrovascular diseases on the incidence of hip or femoral fractures, there is a limited number of studies investigating the relationship between hypertension and hip or femoral fracture. A previous study indicated that hypertension may subtly damage brain structures associated with gait control and balance, potentially leading to falls and subsequent fractures.21 Similarly, hypertension may induce calcium metabolism abnormalities, including increased calcium loss, compensatory activation of the parathyroid glands, and increased transfer of calcium from bones.22 A previous retrospective study confirmed the association between hypertension in the elderly and low bone mineral density at the femoral neck,23 A cross-sectional analysis involving 270 women also indicated that hypertension is an important predictive factor for osteopenia.24 Endothelial cell dysfunction is frequently recognized as a precursor to hypertension25 and plays a critical role in the progression of hypertension.26 Hypertension exacerbates cellular damage, leading to vascular stiffening.27 Prior studies have demonstrated that microvascular endothelial dysfunction can increase bone fragility, thereby elevating the risk of hip fractures.28
It is important to emphasize that the subgroup analysis indicated that even after subsequent administration of therapeutic medications, the risk of secondary hip fracture remained unchanged in patients with hypertension and osteoporosis. During the pharmacological treatment of osteoporosis, anti-resorptive agents such as bisphosphonates are commonly used in clinical practice. Previous studies examining the impact of osteoporosis medication on subsequent fracture risk in non-fractured or high-risk elderly populations have reported conflicting results. Some studies suggested that treatment with bisphosphonates significantly reduced the risk of secondary hip fractures,29 while other reports indicated that using medications such as Strontium ranelate and Ibandronate did not have an immediate impact on fracture risk.30 A cohort study on participants with ischemic heart disease has shown that the use of nitrates can significantly reduce the risk of hip fractures; however, it also noted that only short-acting nitrates or intermittent use of nitrates are effective in lowering this risk.31 In addition to differences in clinical conditions, medication use, and individual constitution among participants, the uncertainty regarding the impact of drugs on fracture risk may also be because a majority of hip or femoral fractures are caused by falls or trips. The variation in elderly fracture risk is not only dependent on drug utilization and disease management but could also be attributed to an increase in fall propensity and gradual loss of protective reflexes.32 Moreover, previous studies have suggested that the increased incidence of hip or femoral fractures among elderly individuals may also be attributed to the concomitant use of multiple medications, which can heighten the risk of drug interactions and adverse events.33
In this study, we examined the key prevention groups that reduce hip or femoral fracture risk in people with chronic conditions and found that where you live, your education level and whether you retire have different effects on your fracture risk. When discussing regional differences, the development of a country and life expectancy may also play a key role in the incidence of hip or femoral fractures.34 A Lancet study of the life expectancy of citizens in 35 industrialized countries found that life expectancy continued to increase in Western European countries,35 improved healthcare, longer life expectancy, and better health databases and case identification could lead to an increase in hip or femoral fractures. While one study showed an increase in hip or femoral fractures among people of low socioeconomic status,36 there is evidence that older people who retired full-time37 and more educated are generally sedentary,38 where a sedentary lifestyle significantly increases the risk of hip or femoral fracture.39
This study highlights the significant impact on public health and clinical practice, with our findings underscoring the crucial role of timely intervention and effective management of CDS in preventing fractures among older adults. For highly educated retirees living in Western Europe, this may make more sense because it could help prevent and screen for hip or femoral fractures earlier.
To our knowledge, this is a preliminary cohort study investigating the relationship between CDS in older adults and hip or femoral fractures. Using a sub-distribution model and specific cause-specific risk models ensures the validity and effectiveness of our approach, confirmed by a series of sensitivity analyses to verify the robustness of our findings.
Our study inevitably has some limitations. There is more than one type of medication for treating hypertension and osteoporosis, and both the dosage regimen and adherence of the patients could not be determined in this study, which may affect the accuracy of the results. Although research indicates that self-reporting is a relatively accurate source for disease diagnosis, it may overlook other sources such as primary care clinics and memory cases, leading to an underestimation of the prevalence of these diseases. Finally, although we conducted multiple sensitivity analyses, there remain some potential confounding factors. Due to data limitations, the present study did not include participants' biological information (blood tests, imaging scans, etc.), which restricted further exploration.
5 Conclusion
In this prospective cohort study of older adults in Europe based on SHARE, we found that hypertension and osteoporosis increase the risk of hip or femoral fracture in the elderly. Moreover, the risk of fractures is associated with geographic location, educational background, and occupational status. These findings contribute to a better understanding of the potential risk factors for hip or femoral fractures and assist policymakers in implementing early intervention measures for the prevention of this condition in the elderly population.
CRediT authorship contribution statement
Yan-Yu Zhu: Conceptualization, Formal analysis, Methodology, Project administration, Software, Writing – original draft. Hai-Fen Wei: Data curation, Methodology, Resources, Software, Validation, Writing – original draft. Sheng Li: Formal analysis, Methodology, Resources, Software, Writing – original draft. Lei Li: Investigation, Software, Validation, Visualization, Writing – review & editing. Peng Wang: Conceptualization, Data curation, Project administration, Supervision, Visualization, Writing – review & editing. Hai-Feng Pan: Funding acquisition, Project administration, Supervision, Visualization, Writing – review & editing.
Consent to participate
Not applicable.
Ethical approval
No need for ethical approval for the use of anonymous open data.
Ethical approval
No need for ethical approval as the use of anonymous open data.
Consent for publication
Not applicable.
Funding statement
This study was funded by grants from the National Natural Science Foundation of China (82273710, 82404354), Research Funds of Center for Big Data and Population Health of IHM (JKS2022017).
References
- Hip fractures among the elderly: causes, consequences and control. Ageing Res Rev. 2003;2(1):57-93.
- [Google Scholar]
- Incidence of and trends in hip fracture among adults in urban China: a nationwide retrospective cohort study. PLoS Med. 2020;17(8)
- [Google Scholar]
- Who breaks their hip? A decade of traumatic hip fracture data. J Orthop. 2025;62:7-12.
- [Google Scholar]
- Incidence of and trends in hip fracture among adults in urban China: a nationwide retrospective cohort study. PLoS Med. 2020;17(8)
- [Google Scholar]
- Associations between multimorbidity and kidney function decline in old age: a population-based cohort study. J Am Geriatr Soc. 2025;73(3):837-848.
- [Google Scholar]
- The association between the ten-year trajectory of multimorbidity and depressive symptoms among the middle-aged and older adults: results from the China health and retirement longitudinal study. J Affect Disord. 2025;370:140-146.
- [Google Scholar]
- Multimorbidity, cognitive phenotypes, and alzheimer's disease plasma biomarkers in older adults: a population-based study. Alzheimer's Dement. 2024;20(3):1550-1561.
- [Google Scholar]
- The impact of multimorbidity and functional limitation on quality of life in patients with heart failure: a multi-site study. J Am Geriatr Soc. 2024;72(6):1750-1759.
- [Google Scholar]
- Association of disease definition, comorbidity burden, and prognosis with hip fracture probability among late-life women. JAMA Intern Med. 2019;179(8):1095-1103.
- [Google Scholar]
- Depression and risk of hip fracture: a systematic review and meta-analysis of cohort studies. Osteoporos Int. 2019;30(6):1157-1165.
- [Google Scholar]
- Prevalence of osteoporosis and incidence of hip fracture in women--secular trends over 30 years. Bmc Musculoskelet Disord. 2010;11:48.
- [Google Scholar]
- A short scale for measuring loneliness in large surveys: results from two population-based studies. Res Aging. 2004;26(6):655-672.
- [Google Scholar]
- Social isolation, loneliness, and all-cause mortality in older men and women. Proc Natl Acad Sci U S A. 2013;110(15):5797-5801.
- [Google Scholar]
- Introduction to the analysis of survival data in the presence of competing risks. Circulation (New York, N Y). 2016;133(6):601-609.
- [Google Scholar]
- Hip fracture risk among community-dwelling elderly people in the United States: a prospective study of physical, cognitive, and socioeconomic indicators. Am J Public Health. 2006;96(7):1210-1218.
- [Google Scholar]
- Osteoporosis in women 45 years and over related to subsequent fractures. Public Health Rep (1896). 1969;84(1):33-38.
- [Google Scholar]
- Cardiovascular disease and hip fracture among older inpatients in beijing, China. BioMed Res Int. 2013;2013
- [Google Scholar]
- Cardiovascular diseases and future risk of hip fracture in women. Osteoporos Int. 2007;18(10):1355-1362.
- [Google Scholar]
- Causal effect of blood pressure on bone mineral density and fracture: a mendelian randomization study. Front Endocrinol. 2021;12
- [Google Scholar]
- The relationships between blood pressure, blood glucose, and bone mineral density in postmenopausal Turkish women. Ther Clin Risk Manag. 2015;11:1641-1648.
- [Google Scholar]
- Pde4b abrogation extenuates angiotensin ii-induced endothelial dysfunction related to hypertension through up-regulation of ampk/sirt1/nrf2/are signaling. Tissue Cell. 2024;91
- [Google Scholar]
- Erbb3 governs endothelial dysfunction in hypoxia-induced pulmonary hypertension. Circulation (New York, N Y). 2024;150(19):1533-1553.
- [Google Scholar]
- Human amnion epithelial cell therapy reduces hypertension-induced vascular stiffening and cognitive impairment. Sci Rep. 2024;14(1):1837.
- [Google Scholar]
- Vascular deficits contributing to skeletal fragility in type 1 diabetes. Front Clin Diabetes Healthc. 2023;4
- [Google Scholar]
- Alendronate adherence and its impact on hip-fracture risk in patients with established osteoporosis in taiwan. Clin Pharmacol Ther. 2011;90(1):109-116.
- [Google Scholar]
- Effects of oral ibandronate administered daily or intermittently on fracture risk in postmenopausal osteoporosis. J Bone Miner Res. 2004;19(8):1241-1249.
- [Google Scholar]
- Hip fracture rate and osteoporosis treatment in ontario: a population-based retrospective cohort study. Arch Osteoporosis. 2024;19(1):53.
- [Google Scholar]
- Geographic trends in incidence of hip fractures: a comprehensive literature review. Osteoporos Int. 2011;22(10):2575-2586.
- [Google Scholar]
- Future life expectancy in 35 industrialised countries: projections with a bayesian model ensemble. Lancet. 2017;389(10076):1323-1335.
- [Google Scholar]
- Is education level, as a proxy for socio-economic position, related to device-measured and self-reported sedentary behavior in european older adults? A cross-sectional study from the sitless project. Front Public Health. 2023;11
- [Google Scholar]
- Changes in sedentary behaviours across the retirement transition: a systematic review. Age Ageing. 2015;44(6):918-925.
- [Google Scholar]
- Sedentary time in us older adults associated with disability in activities of daily living independent of physical activity. J Phys Activ Health. 2015;12(1):93-101.
- [Google Scholar]
- Non-sedentary lifestyle can reduce hip fracture risk among older caucasians adults: the adventist health study-2. Br J Med Med Res. 2015;8(3):220-229.
- [Google Scholar]