Skip to main content Accessibility help
×
Home

Information:

  • Access
  • Cited by 10

Actions:

      • Send article to Kindle

        To send this article to your Kindle, first ensure no-reply@cambridge.org is added to your Approved Personal Document E-mail List under your Personal Document Settings on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part of your Kindle email address below. Find out more about sending to your Kindle. Find out more about sending to your Kindle.

        Note you can select to send to either the @free.kindle.com or @kindle.com variations. ‘@free.kindle.com’ emails are free but can only be sent to your device when it is connected to wi-fi. ‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.

        Find out more about the Kindle Personal Document Service.

        Associations between the dietary intake of antioxidant nutrients and the risk of hip fracture in elderly Chinese: a case–control study
        Available formats
        ×

        Send article to Dropbox

        To send this article to your Dropbox account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your <service> account. Find out more about sending content to Dropbox.

        Associations between the dietary intake of antioxidant nutrients and the risk of hip fracture in elderly Chinese: a case–control study
        Available formats
        ×

        Send article to Google Drive

        To send this article to your Google Drive account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your <service> account. Find out more about sending content to Google Drive.

        Associations between the dietary intake of antioxidant nutrients and the risk of hip fracture in elderly Chinese: a case–control study
        Available formats
        ×
Export citation

Abstract

The role of oxidative stress in skeletal health is unclear. The present study investigated whether a high dietary intake of antioxidant nutrients (vitamins C and E, β-carotene, animal-derived vitamin A, retinol equivalents, Zn and Se) is associated with a reduced risk of hip fracture in elderly Chinese. This 1:1 matched case–control study involved 726 elderly Chinese with hip fracture and 726 control subjects, recruited between June 2009 and May 2013. Face-to-face interviews were conducted to determine habitual dietary intakes of the above-mentioned seven nutrients based on a seventy-nine-item FFQ and information on various covariates, and an antioxidant score was calculated. After adjustment for potential covariates, dose-dependent inverse associations were observed between the dietary intake of vitamin C, vitamin E, β-carotene, and Se and antioxidant score and the risk of hip fracture (P for trend ≤ 0·005). The OR of hip fracture for the highest (v. lowest) quartile of intake were 0·39 (95 % CI 0·28, 0·56) for vitamin C, 0·23 (95 % CI 0·16, 0·33) for vitamin E, 0·51 (95 % CI 0·36, 0·73) for β-carotene, 0·43 (95 % CI 0·26, 0·70) for Se and 0·24 (95 % CI 0·17, 0·36) for the antioxidant score. A moderate-to-high dietary intake of retinol equivalents in quartiles 2–4 (v. 1) was found to be associated with a lower risk of hip fracture (OR range: 0·51–0·63, P< 0·05). No significant association was observed between dietary Zn or animal-derived vitamin A intake and hip fracture risk (P for trend >0·20). In conclusion, a higher dietary intake of vitamins C and E, β-carotene, and Se and a moderate-to-high dietary intake of retinol equivalents are associated with a lower risk of hip fracture in elderly Chinese.

Osteoporotic fractures contribute significantly to the societal disease burden( 1 ). Hip fracture is considered to be the most severe type of osteoporotic fracture due to the high morbidity, mortality and economic cost( 2 4 ). Therefore, prevention strategies for hip fracture are particularly important.

Some studies have suggested that oxidative stress plays an important role in bone resorption. Oxidative stress has been shown in basic studies to increase osteoclastic resorption by inducing the activation of NF-κB( 5 , 6 ), and 8-iso-PGF2α (a biomarker of oxidative stress) concentrations have been reported to be negatively associated with bone mineral density (BMD) in observational studies( 7 ).

Previous studies( 8 10 ) have shown that higher consumption of fruit and vegetables is associated with higher BMD and bone mass and a reduced risk of fractures. Fruit and vegetables are major sources of antioxidants, such as vitamin C and β-carotene. Therefore, a high intake of fruit and vegetables may be a proxy for a high intake of antioxidants. Several epidemiological studies have investigated the relationships between the retinol equivalent of animal-derived vitamin A and plant-derived β-carotene, vitamin C, vitamin E, Zn, and Se and BMD or fracture, but the findings have been inconsistent( 11 19 ). Many studies have found a positive association between antioxidant consumption and bone health( 11 , 14 , 15 ). In contrast, some studies have shown retinol-equivalent and animal-derived vitamin A to be associated with a low BMD or risk of fracture( 16 , 17 ); in the Women's Health Initiative Study, no significant association was found between retinol equivalents, vitamin C, vitamin E or Se and BMD( 12 ), and a longitudinal study also failed to establish a relationship between Zn and BMD( 19 ). Conflicting research findings suggest a potentially complex relationship between serum or plasma antioxidant concentrations and skeletal health( 20 23 ). The different study populations, study designs and sample sizes used may explain the discrepant observations in the studies reported thus far. The majority of previous studies have been conducted in Western populations, and less is known about the association between the intake of antioxidants and skeletal health in Asian populations. The present study investigated the associations between the consumption of antioxidant nutrients, including vitamins C (mg/d) and E (mg/d), retinol equivalents (μg retinol equivalents/d), animal-derived vitamin A (μg/d), β-carotene (μg/d), Zn (mg/d) and Se (μg/d), and the risk of hip fracture in elderly Chinese.

Participants and methods

Study population

The present case–control study was conducted between June 2009 and May 2013 in Guangzhou, Guangdong Province, China. The total study group comprised 1452 recruits from four participating hospitals and communities. A detailed description of the study design has been published previously( 10 , 24 ).

In brief, case participants were newly diagnosed (within the previous 2 weeks) with hip fracture on the basis of X-ray examination. Patients with any of the following conditions were excluded from the study: (1) a high-energy or pathological fracture; (2) a change in dietary habits within the previous 5 years; (3) a chronic disease such as diabetes, CVD, cancer, cognitive disorder, liver cirrhosis, thyroid disorder, renal failure or chronic diarrhoea; (4) current use of exogenous oestrogen, thiazine, corticosteroid or other medications; (5) poor vision that might affect routine activities. Control subjects were individually matched (1:1) by sex and age ( ± 3 years) from the same hospitals or the local communities in the same cities. The controls were recruited through local advertisements and subjects’ referrals and interviewed within 3 months of the enrolment of the corresponding cases. The present study was conducted according to the guidelines laid down in the Declaration of Helsinki, and all procedures involving human subjects were approved by the Ethics Committee of the School of Public Health of Sun Yat-sen University (no. 3 in 2009). Written informed consent was obtained from all study participants.

Data collection

Trained interviewers with relevant medical knowledge conducted face-to-face interviews with the study participants and also took anthropometric measurements. Participants’ sociodemographic characteristics, lifestyle habits, medical history, family history, years since menopause for females, and dietary and supplement intakes were determined by means of structured questionnaires and recorded. Each interviewer completed an equal proportion of interviews between the case group and the control group.

Calculation of dietary antioxidant intakes

Dietary intake information was collected by means of a modified semi-quantitative FFQ, which was used to determine the frequency (‘never’, ‘per year’, ‘per month’, ‘per week’ and ‘per day’) of consumption and amount of seventy-nine food items consumed over the previous year, with a colour picture booklet used as a guide for portion sizes. The average daily intake of a given food item was multiplied by its nutrient content based on the Chinese Food Composition Table 2002( 25 ). For each study participant, daily intake of energy and nutrients was then calculated by totalling the values across all food items. Retinol equivalents included both animal-derived vitamin A and fruit- and vegetable-derived β-carotene, which can be converted to retinol, and the intake was expressed as retinol equivalents (1 μg retinol equivalent = 1 μg of retinol = 12 μg of β-carotene). The validity and reproducibility of the FFQ have been reported elsewhere( 26 ). Correlation coefficients for energy-adjusted nutrients assessed from the questionnaires and six 3 d dietary records in 12 months were computed in the local population, and the correlation coefficients for vitamins A, C and E, retinol and carotene were found to be 0·32, 0·32, 0·25, 0·31 and 0·32, respectively( 26 ).

Assessment of covariates

A face-to-face interview was conducted by a trained interviewer using a structured questionnaire to collect information on the following: age (year); sex (male/female); use of oral contraceptives (OC) and oestrogen (yes or no); education level (primary school or below, secondary school, and high school or above); occupation (full non-physical work, main non-physical work, and main physical labour, full physical labour, and others); household income (Yuan/month per person: ≤ 500, 501–2000, 2001–3000, and >3000); family history of fracture (yes/no); smoking (yes/no); passive smoking (yes/no); alcohol drinking (yes/no); Ca supplement use (yes/no); multivitamin supplement use (yes/no); daily energy intake and intake of selected dietary nutrients (energy-adjusted protein and Ca and P). Subjects who smoked at least one cigarette per d or drank alcohol once a week for at least 6 months were defined as smokers or drinkers. Subjects who had been exposed to other people's tobacco smoking for at least 5 min daily in the previous 5 years were defined as passive smokers. Body height (cm) and weight (kg) were measured in the controls dressed in light clothing and without shoes and self-reported by the case participants. BMI (kg/m2) was then calculated. Daily physical activity (metabolic equivalent h/d) was estimated using a 24 h physical activity questionnaire containing nineteen items( 27 ).

Statistical analyses

The characteristics of the case participants and control subjects were compared using the t test for continuous variables and Pearson's χ2 test for categorical variables. The distribution of energy and nutrient intake data was normalised by log transformation. The dietary intakes of all nutrients were adjusted for total energy intake using a residual method( 28 ). An antioxidant score (ranging between 4 and 16) was calculated by summing the quartile points of each nutrient to evaluate the combined association of vitamins C and E, β-carotene, and Se. The participants were then categorised into quartiles (Q1–Q4) of intake according to the consumption of each energy-adjusted antioxidant or the score in control subjects, and the cut-offs were applied for the classification of the case participants. The lowest quartile (Q1) was used as the reference.

As the matching of socio-economic factors (education level, household income and occupation) was not successful, both non-conditional and conditional regression methods were used and compared. Non-conditional logistic regression, as in the INTERHEART study( 29 ), was used to estimate the association between the intake of selected antioxidants and the risk of hip fracture as it is a more conservative approach.

Antioxidant nutrient intakes and antioxidant scores were analysed as continuous variables as well as categorical quartile variables to calculate OR and 95 % CI. The lowest quartile was considered as the reference quartile in the categorical variable analysis. Trend tests were carried out by modelling the mean values of the intake of each antioxidant nutrient or antioxidant score in the control groups as a continuous variable. Models were adjusted for age, sex+drugs (defined as men and women using OC or oestrogen and women not using OC and oestrogen; model 1). Subsequent models were further adjusted for BMI, education level, occupation, household income, family history of fracture, smoking and alcohol drinking, passive smoking, Ca and multivitamin supplement use, physical activity, daily intakes of energy and energy-adjusted protein and Ca and P (model 2). All covariates were selected using the forward stepwise method.

Interaction analyses were conducted to explore whether the above associations varied in different sexes (male or female) and with the source of the control subjects (community or hospital), and the stratified results by sex (male or female) and the source of the control subjects are reported. Years since menopause, former use of oestrogen and use of OC were further adjusted by female sex in the multivariate analysis. Interaction between sex and the source of the control subjects and the antioxidants studied was tested using the likelihood ratio test. A two-sided P value <0·05 was considered significant. Considering type 1 error caused by multiple testing, P values were adjusted using Bonferroni correction. P adjusted = 0·05/number of tests. All analyses were conducted using SPSS version 17.0 (SPSS, Inc.).

Results

Study participants

A total of 1402 potential case patients and 1215 potential control subjects from participating hospitals and local communities were screened, and 501 (35·7 %) of the former and 355 (29·2 %) of the latter were found to not meet the study criteria. An additional 175 case patients and 134 control subjects who did meet the eligibility criteria were excluded for the following reasons: difficulty in communicating (forty-eight case patients and twenty-one control subjects); unreasonable energy intake (nineteen case patients and sixteen control subjects; reasonable range: 3347–16 736 kJ/d (800–4000 kcal/d) for males and 2092–14 644 kJ/d (500–3500 kcal/d) for females); refusal to participate (108 case patients and twenty-four control subjects); a history of fracture (seventy-three control subjects). Thus, 726 case patients and 726 control subjects (542 recruited from local communities and 184 recruited from hospitals) were included in the final analysis. Among the community-based controls, 6 % were attendants or relatives of a patient from a non-hip fracture ward without any diseases related to the studied factors or bone health and 94 % were recruited from the local communities of the same cities from where the cases came from.

The cases and controls had similar ages of 70 and 71 years in men and women, respectively. The mean values of dietary intakes of selected antioxidant nutrients were 474 and 476 μg retinol equivalents/d, 102 and 106 mg/d for vitamin C, 11 and 10 mg/d for vitamin E, 12·2 and 11·5 mg/d for Zn, and 48 and 48 μg/d for Se among men and women in the control group (Table 1). The dietary intake levels met 59 and 68 % (retinol equivalents), 79 and 71 % (vitamin E), and 96–106 % (vitamin C, Zn and Se) of the values recommended by the Chinese Nutrition Society in 2000.

Table 1 Demographics, lifestyle characteristics and selected hip fracture risk factors of the study population (Mean values and standard deviations; number of participants and percentages)

MET, metabolic equivalent.

* Evaluated by t tests.

Physical activities included daily occupational activities, leisure-time activities and household chores, evaluated by MET-h/d.

Evaluated by χ2 tests.

§ Occupation was categorised into five levels on the basis of labour model.

Smoker was defined as having smoked at least one cigarette daily for at least 6 consecutive months.

Passive smoking was defined as having been exposed to other people's tobacco smoking for at least 5 min daily in the previous 5 years.

** Alcohol drinker was defined as having had alcoholic beverages (wine, beer or Chinese spirits) at least once a week for at least 6 consecutive months.

The characteristics of the participants stratified by case–control status are also given in Table 1. Overall, patients with hip fracture were more likely than control subjects to have a low BMI, to have low levels of education and household income, to engage in physical work, to be smokers, and to have consumed fewer multivitamin and Ca supplements. A trend of low physical activity and low OC and oestrogen use was observed in the female case patients.

Associations between the dietary intake of the studied antioxidant nutrients and the risk of hip fracture

In model 1, a significant inverse association was observed between the dietary intake of each studied antioxidant nutrient and antioxidant score and the risk of hip fracture (P for trend < 0·001–0·035; Table 2). After adjustment for age, sex, BMI, socio-economic factors, family history of fracture, lifestyle habits, Ca and multivitamin supplement use, physical activity and some dietary factors, the dose-dependent inverse associations between the dietary intake of vitamin C, vitamin E, β-carotene, and Se and antioxidant score and the risk of hip fracture were found to remain significant (P for trend ≤ 0·005). The OR for the highest v. lowest quartiles of vitamin C, vitamin E, β-carotene, and Se intake and antioxidant score were 0·39 (95 % CI 0·28, 0·56), 0·23 (95 % CI 0·16, 0·33), 0·51 (95 % CI 0·36, 0·73), 0·43 (95 % CI 0·26, 0·70) and 0·24 (95 % CI 0·17, 0·36), respectively. A moderate-to-high dietary intake of retinol equivalents (animal- and plant-derived retinol combined) in quartiles 2–4 (v. quartile 1) was found to be associated with a reduced hip fracture risk (OR range: 0·51–0·63, all P< 0·05). No significant association was found between the dietary intake of other antioxidant nutrients (animal-derived vitamin A and Zn) and the risk of hip fracture (P for trend 0·661 and 0·277, respectively). Similar results were obtained in the conditional logistic regression analyses (Table S1, available online) as well as when exposure variables were analysed as continuous variables (P range < 0·001–0·040 for vitamin C, vitamin E, Se, and β-carotene and antioxidant score; Table S2, available online).

Table 2 Risk of hip fracture for quartiles (Q) of antioxidant intake in the study population (Number of cases and controls; odds ratios and 95 % confidence intervals)

* Significant levels: P< 0·006, adjusted using Bonferroni correction.

Mean intake of vitamin A in male/female controls, which was adjusted for daily energy intake using the residual method, and the mean of daily energy intake was 5669 kJ (1355 kcal) for males and 5347 kJ (1278 kcal) for females.

OR I: from unconditional logistic model adjusted for age and sex+drugs (defined as men and women using oral contraceptives (OC) or oestrogen and women not using OC and oestrogen).

§ OR II: from unconditional logistic model adjusted for age; sex+drugs; BMI; educational level; occupation; household income; family history of fracture; smoking; passive smoking; alcohol drinking; Ca supplement use; multivitamin supplement use; physical activity; daily energy intake; and dietary intake of selected nutrients (protein and Ca and P; energy-adjusted), and all covariates were selected using the forward stepwise method.

In the stratified analysis, no significant interactions were found between the dietary intake of the studied antioxidant nutrients and sex or source of the control subjects (Table 3; P interactions >0·004, 0·05/fourteen tests).

Table 3 Risk of hip fracture for quartiles (Q) of vitamin and mineral intakes stratified by sex and source of controls in the study population (Odds ratios and 95 % confidence intervals)

* Significant level: P>0·004 ( = 0·05/fourteen tests), adjusted using Bonferroni correction.

Study size: male, 177 pairs; female, 549 pairs; hospital controls, 184 pairs; community controls, 542 pairs.

OR from multivariate unconditional logistic regression models. The following covariates were adjusted for: age; BMI; educational level; occupation; household income; family history of fracture; smoking; passive smoking; alcohol drinking; Ca supplement use; multivitamin supplement use; physical activity; daily energy intake; dietary intake of selected nutrients (protein and Ca and P; energy-adjusted). For women, years since menopause, oral contraceptive use, and former use of oestrogen were further adjusted for using the stepwise forward method.

Discussion

In the present study, a reduced risk of hip fracture was found to be associated with a high dietary intake of vitamins C and E, β-carotene, and Se and with a moderate dietary intake of retinol equivalents. Similar inverse associations were found when antioxidant scores were analysed.

Many epidemiological studies have found that vitamins C and E have beneficial effects on skeletal health( 11 , 13 , 14 ). A nested case–control study of 1120 elderly Swedish women aged 40–76 years included in the Swedish Mammography Cohort showed that a low intake of vitamins C and E increased the risk of hip fracture in current smokers after adjustment for age, weight and other osteoporosis risk factors( 13 ). Similar results were obtained in the Utah Study of Nutrition and Bone Health (USNBH), which examined the risk of hip fracture in 2564 Americans( 11 ), in the Framingham Osteoporosis Study of 4-year bone loss( 14 ), in an interventional study of BMD( 30 ) and in a cross-sectional study( 22 ). Consistent with the results of these studies, we found a significant inverse association between the increased intake of vitamins C and E and the risk of hip fracture. However, the protective effect exerted by vitamins C and E against hip fracture and BMD was not observed in the Women's Health Initiative Study( 12 ), in the fracture intervention trial study( 31 ), or in a case–control study of 329 American women after adjustment for important covariates( 32 ). The reasons for the between-study differences remain unclear. Differences in the study designs and in the methods used for dietary intake assessment, as well as the varied populations, might in part explain the discrepancies. Vitamins C and E are important dietary antioxidants. They might improve bone health by scavenging free radicals( 33 ), which have been found to be involved in rodent bone metabolism and to enhance bone resorption( 34 ). In addition, there is much evidence suggesting that vitamins C and E play a role in the formation of collagen matrices( 35 , 36 ). Therefore, they are needed for normal bone development.

Our finding of an inverse association between the dietary intake of β-carotene and the risk of hip fracture is congruent with previously reported findings( 11 , 37 ). In the USNBH, Zhang et al. ( 11 ) observed an inverse association between the intake of β-carotene and the risk of osteoporotic hip fracture in 2564 Americans aged ≥ 50 years. Similar favourable effects of dietary β-carotene( 37 ), serum β-carotene concentrations( 38 ) and plasma β-carotene concentrations( 21 ) on BMD or BMD changes have been found. Furthermore, a cross-sectional study showed dietary β-carotene intake to be inversely correlated with the excretion of deoxypyridinoline (a marker of bone resorption)( 39 ). However, neither dietary intake nor the serum concentration of β-carotene was found to be associated with hip fracture risk or bone loss in the Nurses’ Health Study involving 72 337 postmenopausal women( 17 ), in the Aberdeen Prospective Osteoporosis Screening Study( 19 ), in the Uppsala Longitudinal Study of Adult Men( 20 ), in the Framingham Osteoporosis Study( 40 ) or in the Swedish Mammography Cohort( 13 ). Vitamin C and many other phytochemicals coexist with β-carotene in foods. Although the positive association between β-carotene and reduced hip fracture risk might be attributed in part to its antioxidant effects( 33 ), many studies have shown phytochemicals such as lycopene to have positive effects on hip fracture risk( 40 ) and BMD( 21 ). Further studies are needed to clarify the independent association of β-carotene with hip fracture risk by well adjusting for the coexisting phytochemicals.

Studies on the effect of retinol-equivalent intake on skeletal health have yielded inconsistent results. A population-based cohort study of 1526 American women aged ≥ 55 years showed an inverse U-shaped association between animal-derived vitamin A and BMD, particularly at the femoral neck( 18 ). Opotowsky & Bilezikian( 41 ) also described a U-shaped association between serum vitamin A concentrations and hip fracture risk. Many studies have shown that retinol-equivalent and animal-derived vitamin A in high doses or high serum vitamin A concentrations accelerate bone loss and increase fracture risk( 16 , 17 , 20 ). Consistent with these findings, we found that a moderate intake of retinol equivalents had the strongest positive effect on hip fracture risk. However, we did not find a deleterious effect for the highest quartile, possibly because of a relatively low intake of retinol equivalents in the present study population in comparison with that in other populations( 17 , 19 ), and the highest intake was observed for the plant-derived retinol equivalents. Nevertheless, several studies have failed to establish a relationship between vitamin A and skeletal health( 21 , 42 ). Several biological mechanisms might explain the potential U-shaped association. Vitamin A deficiency has been shown to increase both osteoclastic and osteoblastic activities, resulting in abnormal bone growth in animals( 43 ). On the other hand, there is much evidence in rodents showing that excessive vitamin A or synthetic retinoid is associated with increased osteoclastic bone resorption( 44 , 45 ). These findings suggest that retinol equivalents are required for skeletal growth, but hypervitaminosis A may have a deleterious effect on skeletal health.

Se supplementation can reinforce endogenous antioxidative systems( 46 ); thus, it may improve bone health by defending against oxidative stress. We found Se to be inversely associated with the risk of hip fracture, and this association has also been observed in other studies( 11 ). However, no significant association was found in the Swedish Mammography Cohort( 13 ). The null association might be attributed in part to the pronounced errors in the assessment of Se intake because of the variation in the Se content of foods between different countries and different regions( 47 ).

To assess the combined association of vitamins C and E, β-carotene, and Se, we further examined the association of the antioxidant score and the risk of hip fracture by summing the quartile points of each nutrient. A more significant inverse association was observed when compared with that observed for individual nutrients, except vitamin E, suggesting that the combination of vitamin C, β-carotene and Se might be more efficient than individual nutrients. We also assessed whether the inverse association was modified by sex and the source of the control subjects. No significant interaction was found after adjusting for the number of multiple tests, indicating similar associations across the subgroups by these variables. However, we had insufficient power to detect the interactions between some studied nutrients and sex or the source of the control subjects with regard to the risk of hip fracture. For interactions between antioxidant nutrients and sex, we had a power < 50 % for retinol equivalents, β-carotene and vitamin C, but >90 % for the remaining antioxidant nutrients to detect an OR of 0·7, with an α error of 0·004, assuming an ordinal trend across quartiles of intake. For interactions between antioxidant nutrients and the source of the control subjects, we had a power < 30 % for retinol equivalents and β-carotene and >90 % for the remaining exposures( 48 ).

The present study has several limitations. In a case–control study, the time period between the exposure and the outcome is unclear. Nevertheless, this factor might have been mitigated in the present study because only new cases were selected; potential case patients and control subjects with a chronic disease that could have altered dietary habits or nutritional factors were excluded, and adults maintain relatively stable long-term dietary habits( 49 ). Moreover, recall bias might affect the results. We attempted to minimise recall bias through face-to-face interviews and by visual aids for the assessment of portion sizes. We also controlled interviewer bias by having each researcher interview a similar proportion of cases and controls. Another limitation was the assumptions made in the calculation of antioxidant values for food items. Antioxidant concentrations varied across foods that were combined in one item. When this occurred, we assigned the mean value of the contributing foods. In addition, limited information was collected about the dietary intake of oil, which is a rich source of vitamin E. Measurement errors could have resulted in the misclassification of the participants. However, such errors might have reduced rather than strengthened the observed association. In addition, the calculation of antioxidant score from the intake of antioxidant nutrients could lead to misclassification, and we assumed all the included antioxidants to have contributed equally to the association. Finally, as the study was hospital-based, selection bias could not be excluded completely, despite the fact that the case patients were recruited from various types of hospitals and controls were mainly recruited from the local communities.

In conclusion, the results of the present study suggest that a high dietary intake of vitamin C, vitamin E, β-carotene, and Se and a moderate-to-high dietary intake of retinol equivalents may protect against hip fracture in elderly Chinese.

Supplementary material

To view supplementary material for this article, please visit http://dx.doi.org/10.1017/S0007114514002773

Acknowledgements

The authors are grateful to Dr Wei-fu Ouyang and Sulan Tu for helping with data collection and the doctors and nurses in the above-mentioned hospitals for facilitating both the recruitment of participants and the interviews.

The present study was supported by the National Natural Science Foundation of China (Y.-m. C., grant no. 81072299, 81273049 and 30872100). The sponsor had no role in the design and analysis of the study or in the writing of this article.

The authors’ contributions are as follows: Y.-m. C. conceived and designed the study and critically revised the manuscript; L.-l. S. analysed the data and wrote the article; B.-l. L., H.-l. X., F. F., W.-z. Y., B.-h. W. and W.-q. X. carried out the study and data cleansing and wrote the article.

None of the authors has any conflicts of interest to declare.

References

1 Johnell, O & Kanis, JA (2006) An estimate of the worldwide prevalence and disability associated with osteoporotic fractures. Osteoporos Int 17, 17261733.
2 Johnell, O & Kanis, J (2005) Epidemiology of osteoporotic fractures. Osteoporos Int 16, S3S7.
3 Johnell, O & Kanis, JA (2004) An estimate of the worldwide prevalence, mortality and disability associated with hip fracture. Osteoporos Int 15, 897902.
4 Cooper, C, Campion, G & Melton, LJ III (1992) Hip fractures in the elderly: a world-wide projection. Osteoporos Int 2, 285289.
5 Hall, TJ, Schaeublin, M, Jeker, H, et al. (1995) The role of reactive oxygen intermediates in osteoclastic bone resorption. Biochem Biophys Res Commun 207, 280287.
6 Franzoso, G, Carlson, L, Xing, L, et al. (1997) Requirement for NF-kappa B in osteoclast and B-cell development. Genes Dev 11, 34823496.
7 Basu, S, Michaelsson, K, Olofsson, H, et al. (2001) Association between oxidative stress and bone mineral density. Biochem Biophys Res Commun 288, 275279.
8 Tucker, KL, Hannan, MT, Chen, H, et al. (1999) Potassium, magnesium, and fruit and vegetable intakes are associated with greater bone mineral density in elderly men and women. Am J Clin Nutr 69, 727736.
9 Chen, YM, Ho, SC & Woo, JLF (2006) Greater fruit and vegetable intake is associated with increased bone mass among postmenopausal Chinese women. Br J Nutr 96, 745751.
10 Xie, HL, Wu, BH, Xue, WQ, et al. (2013) Greater intake of fruit and vegetables is associated with a lower risk of osteoporotic hip fractures in elderly Chinese: a 1:1 matched case–control study. Osteoporos Int 24, 28272836.
11 Zhang, JJ, Munger, RG, West, NA, et al. (2006) Antioxidant intake and risk of osteoporotic hip fracture in Utah: an effect modified by smoking status. Am J Epidemiol 163, 917.
12 Wolf, RL, Cauley, JA, Pettinger, M, et al. (2005) Lack of a relation between vitamin and mineral antioxidants and bone mineral density: results from the Women's Health Initiative. Am J Clin Nutr 82, 581588.
13 Melhus, H, Michaelsson, K, Holmberg, L, et al. (1999) Smoking, antioxidant vitamins, and the risk of hip fracture. J Bone Miner Res 14, 129135.
14 Sahni, S, Hannan, MT, Gagnon, D, et al. (2008) High vitamin C intake is associated with lower 4-year bone loss in elderly men. J Nutr 138, 19311938.
15 Hall, SL & Greendale, GA (1998) The relation of dietary vitamin C intake to bone mineral density: results from the PEPI study. Calcif Tissue Int 63, 183189.
16 Melhus, H, Michaelsson, K, Kindmark, A, et al. (1998) Excessive dietary intake of vitamin A is associated with reduced bone mineral density and increased risk for hip fracture. Ann Intern Med 129, 770778.
17 Feskanich, D, Singh, V, Willett, WC, et al. (2002) Vitamin A intake and hip fractures among postmenopausal women. JAMA 287, 4754.
18 Promislow, JHE, Goodman-Gruen, D, Slymen, DJ, et al. (2002) Retinol intake and bone mineral density in the elderly: the Rancho Bernardo Study. J Bone Miner Res 17, 13491358.
19 Macdonald, HM, New, SA, Golden, MH, et al. (2004) Nutritional associations with bone loss during the menopausal transition: evidence of a beneficial effect of calcium, alcohol, and fruit and vegetable nutrients and of a detrimental effect of fatty acids. Am J Clin Nutr 79, 155165.
20 Michaelsson, K, Lithell, H, Vessby, B, et al. (2003) Serum retinol levels and the risk of fracture. N Engl J Med 348, 287294.
21 Maggio, D, Polidori, MC, Barabani, M, et al. (2006) Low levels of carotenoids and retinol in involutional osteoporosis. Bone 38, 244248.
22 Maggio, D, Barabani, M, Pierandrei, M, et al. (2003) Marked decrease in plasma antioxidants in aged osteoporotic women: results of a cross-sectional study. J Clin Endocrinol Metab 88, 15231527.
23 Simon, JA & Hudes, ES (2001) Relation of ascorbic acid to bone mineral density and self-reported fractures among US adults. Am J Epidemiol 154, 427433.
24 Fan, F, Xue, WQ, Wu, BH, et al. (2013) Higher fish intake is associated with a lower risk of hip fractures in Chinese men and women: a matched case–control study. PLOS ONE 8, e56849.
25 Yang, YX, Wang, GY & Pan, XC (2002) China Food Composition Table. Beijing: Peking University Medical Press.
26 Zhang, C-X & Ho, SC (2009) Validity and reproducibility of a food frequency questionnaire among Chinese women in Guangdong province. Asia Pac J Clin Nutr 18, 240250.
27 Wang, P, Chen, YM, He, LP, et al. (2012) Association of natural intake of dietary plant sterols with carotid intima–media thickness and blood lipids in Chinese adults: a cross-section study. PLOS ONE 7, e32736.
28 Willett, WC (1998) Implications of total energy intake for epidemiologic analysis. In Nutritional Epidemiology, 2nd ed., pp. 273–301 [WC Willett, editor]. New York, NY: Oxford University Press.
29 Yusuf, S, Hawken, S, Ounpuu, S, et al. (2004) Effect of potentially modifiable risk factors associated with myocardial infarction in 52 countries (the INTERHEART study): case–control study. Lancet 364, 937952.
30 Chuin, A, Labonte, M, Tessier, D, et al. (2009) Effect of antioxidants combined to resistance training on BMD in elderly women: a pilot study. Osteoporos Int 20, 12531258.
31 Leveille, SG, LaCroix, AZ, Koepsell, TD, et al. (1997) Dietary vitamin C and bone mineral density in postmenopausal women in Washington State, USA. J Epidemiol Community Health 51, 479485.
32 Nieves, JW, Grisso, JA & Kelsey, JL (1992) A case–control study of hip fracture: evaluation of selected dietary variables and teenage physical activity. Osteoporos Int 2, 122127.
33 Fairfield, KM & Fletcher, RH (2002) Vitamins for chronic disease prevention in adults: scientific review. JAMA 287, 31163126.
34 Garrett, IR, Boyce, BF, Oreffo, RO, et al. (1990) Oxygen-derived free radicals stimulate osteoclastic bone resorption in rodent bone in vitro and in vivo . J Clin Invest 85, 632639.
35 Schwartz, ER (1979) Effect of vitamins C and E on sulfated proteoglycan metabolism and sulfatase and phosphatase activities in organ cultures of human cartilage. Calcif Tissue Int 28, 201208.
36 Kipp, DE, McElvain, M, Kimmel, DB, et al. (1996) Scurvy results in decreased collagen synthesis and bone density in the guinea pig animal model. Bone 18, 281288.
37 Sahni, S, Hannan, MT, Blumberg, J, et al. (2009) Inverse association of carotenoid intakes with 4-y change in bone mineral density in elderly men and women: the Framingham Osteoporosis Study. Am J Clin Nutr 89, 416424.
38 Sugiura, M, Nakamura, M, Ogawa, K, et al. (2008) Bone mineral density in post-menopausal female subjects is associated with serum antioxidant carotenoids. Osteoporos Int 19, 211219.
39 New, SA, Robins, SP, Campbell, MK, et al. (2000) Dietary influences on bone mass and bone metabolism: further evidence of a positive link between fruit and vegetable consumption and bone health? Am J Clin Nutr 71, 142151.
40 Sahni, S, Hannan, MT, Blumberg, J, et al. (2009) Protective effect of total carotenoid and lycopene intake on the risk of hip fracture: a 17-year follow-up from the Framingham Osteoporosis Study. J Bone Miner Res 24, 10861094.
41 Opotowsky, AR & Bilezikian, JP (2004) Serum vitamin A concentration and the risk of hip fracture among women 50 to 74 years old in the United States: a prospective analysis of the NHANES I follow-up study. Am J Med 117, 169174.
42 Barker, ME, McCloskey, E, Saha, S, et al. (2005) Serum retinoids and beta-carotene as predictors of hip and other fractures in elderly women. J Bone Miner Res 20, 913920.
43 Mellanby, E (1941) Skeletal changes affecting the nervous system produced in young dogs by diets deficient in vitamin A. J Physiol 99, 467486.
44 Frankel, TL, Seshadri, MS, McDowall, DB, et al. (1986) Hypervitaminosis A and calcium-regulating hormones in the rat. J Nutr 116, 578587.
45 Kneissel, M, Studer, A, Cortesi, R, et al. (2005) Retinoid-induced bone thinning is caused by subperiosteal osteoclast activity in adult rodents. Bone 36, 202214.
46 Tapiero, H, Townsend, DM & Tew, KD (2003) The antioxidant role of selenium and seleno-compounds. Biomed Pharmacother 57, 134144.
47 Monsen, ER (2000) Dietary reference intakes for the antioxidant nutrients: vitamin C, vitamin E, selenium, and carotenoids. J Am Diet Assoc 100, 637640.
48 Foppa, I & Spiegelman, D (1997) Power and sample size calculations for case–control studies of gene–environment interactions with a polytomous exposure variable. Am J Epidemiol 146, 596604.
49 MacDonald, HM, New, SA & Reid, DM (2005) Longitudinal changes in dietary intake in Scottish women around the menopause: changes in dietary pattern result in minor changes in nutrient intake. Public Health Nutr 8, 409416.