IJE Advance Access originally published online on July 26, 2007
International Journal of Epidemiology 2007 36(5):1143-1150; doi:10.1093/ije/dym149
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Experience of famine and bone health in post-menopausal women
1Department of Community and Family Medicine, School of Public Health, The Chinese University of Hong Kong, Hong Kong SAR.
2Jockey Club Centre for Osteoporosis Care and Control, School of Public Health, The Chinese University of Hong Kong, Hong Kong SAR.
3Department of Orthopaedic and Traumatology, The Chinese University of Hong Kong, Hong Kong SAR.
* Corresponding author. Department of Community and Family Medicine, 4/F, School of Public Health, Prince of Wales Hospital, Shatin, Hong Kong. E-mail: cwkfrank{at}cuhk.edu.hk
| Abstract |
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Background Famines have occurred in all areas of the world in every period of history. Many studies have shown that poor growth and development and adverse environmental conditions in childhood are associated with osteoporosis in later life. However, little information is available on the relation between famine and bone health.
Methods This study examines the hypothesis that past experience of famine has an adverse impact on bone health, using data from Ms Os (Hong Kong), a large cohort study on osteoporosis in Asian women. There were 1826 Hong Kong women aged 65 years or older recruited from the community. A standardized, structured interview and DXA were performed. Subjects who had experienced famine tended to have lower levels of education, social status and current daily calcium intake. They also have higher rates of cigarette consumption, depression and coronary heart disease.
Results After adjustment for confounders, we found that subjects who had experienced famine have a significantly higher rate of developing osteoporosis than those who had not.
Conclusions We conclude that past exposure to famine, especially in childhood, is associated with osteoporosis.
Keywords Starvation, Hong Kong, osteoporosis, post-menopausal, women, Asian Continental Ancestry Group
Accepted 21 June 2007
| Introduction |
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Osteoporosis is a significant public health problem in older women worldwide. It increases the risk of fragility fracture leading to increase mortality and morbidity and a considerable burden to the health care system.1 It has been estimated that by the year 2050, the number of hip fractures will be 3- to 4-fold higher than present, where half of them will occur in Asia.2
The risk of osteoporotic fracture is determined by two main factors: the peak bone mass in adulthood and the rate of bone loss with ageing.3 During World War II, many provinces in China and Hong Kong were occupied by Japan. Many older women who were children at that time were exposed to famine. Famine also occurred in China for various other reasons. Famine does not simply refer to lack of foods, hunger and starvation, it also relates to economic disruption, social breakdown and destitution.4 Recent studies have demonstrated that children with poor nutrition are associated with low peak bone accretion.5,6 In addition, low education level is found to be associated with low bone mineral density among post-menopausal Chinese women.7 To the authors knowledge, no previous studies have been conducted to investigate the relation between famine and bone health. We hypothesize that past exposure to famine increases the risk of osteoporosis, adjusting for confounding factors, using data from Ms Os (Hong Kong), the largest cohort study on osteoporosis for Asian women to date.
| Methods |
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Subjects
Subjects in the current study were from two projects, namely Mr Os and Ms Os, which consist of 2000 Hong Kong Chinese men and women, respectively. The subjects were 65 years of age or older when they were recruited between January 2002 and December 2003 for a study in osteoporosis. Stratified sampling was used in order to obtain approximately one-third of the subjects in each of the following age groups: 65–69, 70–74 and
75 years. All eligible subjects were community-dwelling and ambulatory. Recruitment notices were posted in the housing estates and community elderly centres. Subjects were invited to the research centre for interviews and examinations. Informed consent was obtained on a one-to-one basis. This study was approved by the Joint Chinese University of Hong Kong and the New Territories East Cluster Clinical Research Ethics Committee.
Data collection
Trained interviewers conducted face-to-face interviews based on a structured and validated questionnaire. It covered socio-demographic data, the highest education level that they have obtained and a comprehensive medical history and drug history. Famine history was obtained by directly asking subjects whether they had or had not experienced famine. If subjects claimed that they had previous experience, they will be required to describe details of the exposure including which year they were exposed to and how long did it last for. We considered subjects to have experienced famine exposure if they had a caloric restriction for at least 1 year. The social economic status was assessed by the MacArthur Scale of subjective social status, which was a drawing of a ladder with 10 rungs. People who were the best off would be on the top of the ladder and the worst off would be at the bottom. Subjects were asked to think about their position in the ladder and asked to place an X on the rung to represent where they thought that they stood in the ladder.8 Lifestyle factors included smoking and alcoholic consumption; dietary intake was assessed by a modified version of the Block Food-Frequency questionnaire, based on data obtained in the Hong Kong Adult Dietary Survey in 1995.9 The Physical Activity Scale for the Elderly (PASE) questionnaire 10 and the validated Chinese version of Geriatric Depression Scale (GDS) 11 were used to measure the level of physical activity and depression respectively.
Anthropometric and bone mineral density measurements
Body weight was measured, with subjects wearing a light gown, by the Physician Balance Beam Scale (Healthometer, IL, USA). Height was measured by the Holtain Harpenden standiometer (Holtain, Crosswell, UK). The BMD of the lumber spine (L1–L4) and total hip were measured by dual-energy X-ray absorptiometry using Hologic QDR-4500W densitometer (Hologic, Waltham, MA, USA). The coefficient of variation in our laboratory at the lumbar spine and the total hip was 0.9 and 0.7%, respectively.12 Osteoporosis was defined as the BMD of 0.619 g/cm2 at total hip and/or 0.722 g/cm2 at the lumbar spine using Hong Kong young women as the reference population.13
Statistical analysis
We used independent t-tests to analyse continuous variables and the chi-squared tests for categorical variables. A logistic regression was used to add all potential variables, with past exposure to famine, social status and educational level entered into the model step by step. A linear regression was also used to detect the change of femoral BMD (aeral and volumetric) with past exposure to famine, social status and educational level entered into the model step by step. Path analysis was used to show the odds ratio between different variables in the final model.
| Results |
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Descriptive statistics
Subjects characteristics are shown in Table 1. We found that subjects who had experienced famine have a significantly higher rate of developing osteoporosis than those who had not (48.3 vs 43%, P = 0.049). They have a lower femoral neck bone mineral content (BMC) (2.7 vs 2.8 g, P = 0.031) and a lower femoral neck BMD (0.58 vs 0.59 g/cm2, P = 0.024). They were more likely to have a lower social economic status (43.4 vs 31%, P < 0.001), a lower education level (88.6 vs 74.6, P < 0.001), a lower daily calcium intake (551 vs 602.9 mg/day, P < 0.001), and they were shorter (150.4 vs 151.6 cm, P < 0.001).
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They also had a higher rate of cigarette consumption (2.4 vs 0.9%, P = 0.019), a higher prevalence of depression (11.5 vs 7.8%, P = 0.010) and a higher rate of coronary heart disease (15.6 vs 11.1%, P = 0.005) than subjects who had not experienced famine. There were no significant differences in age, weight, number of standard drink per week, PASE, medical history of chronic obstructive pulmonary disease or asthma, thyroid disease, use of medication such as thiazide diuretic or corticosteroid between subjects who had experienced famine and those who had not.
Multiple regression analysis
The logistic regression model was shown in Table 2. In model A, we found that subjects who had experienced famine have a higher risk of developing osteoporosis [odds ratio (OR) = 1.25; 95% confidence interval (CI): 1.01–1.54] than those who had not, after we adjusted for age (per 5 years), body weight (in kilograms), height (in centimetres), calcium intake (in milligrams/day), current cigarette smoking, current use of alcohol and depression. The addition of socioeconomic factors to the model, which was shown in model B, did not change the OR significantly. We further added the education factor to the model as shown in model C. We found that the association between famine and osteoporosis became non-significant when education was entered into the regression model.
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Two linear regression models were shown in Tables 3 and 4. In model A in Table 3, we found that subjects who had experienced famine have a higher loss in femoral neck BMD (percentage change –1.38; 95% CI: –2.72, –0.03) than who had not after we adjusted for age (per 5 years), body weight (in kilograms), height (in centimetres), calcium intake (in milligrams/day), current cigarette smoking, current use of alcohol, depression and coronary heart disease. However, it became non-significant when the socioeconomic factor (model B, Table 3) and the education factor (model C, Table 3) were added.
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In addition, we also found that subjects who had experienced famine have a higher loss in femoral volumetric BMD which was shown in model A (Table 4) (percentage change –1.66, 95% CI: –3.24, –0.08), than those who had not after the adjustment of other factors same as model A (Table 3). However, it became non-significant when the socioeconomic factor (model B, Table 3) and the education factor (model C, Table 3) were added.
Path analysis
Path analysis model was developed to explore the effect on the inter-relationship of osteoporosis among all variables. To avoid confusion, a simplified path diagram is shown in Figure 1. The experience of famine was positively associated with lower education level (standardized regression coefficient = 0.163, P < 0.001) and lower social economical status (standardized regression coefficient = 0.083, P = 0.001) but negatively associated with femoral neck BMD (standardized regression coefficient = – 0.035) than those who had not. On the other hand, a lower education level were positively associated with famine exposure (standardized regression coefficient = 0.163, P < 0.001) and lower social economical status (standardized regression coefficient = 0.152, P < 0.001), but negatively associated with lower femoral neck BMD (standardized regression coefficient = –0.015).
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Analysis for data of men
We also analysed the data of men from the same cohort independently from women, namely Mr Os. It was found that there is an interaction between female/male and exposure to famine (OR = 1.49, 95% CI: 1.02, 2.18, P = 0.038). The characteristics for men were shown in Table 1. In contrast with female subjects, male subjects who had no experience in famine and those who had experience in famine did not differ in total hip BMC (33.7 vs 33.6 g, P = 0.618), total hip BMD (0.86 vs 0.86 g/cm3, P = 0.936), femoral neck BMC (3.7 vs 3.7 g, P = 0.588) nor femoral neck BMD (0.69 vs 0.69 g/cm3, P = 0.770). Likewise, male subjects had experience in famine and those who had not are not statistically different in osteoporosis status with a P-value of 0.479. In addition, logistic regression analysis for men gave no significant findings as shown in Table 2.
| Discussion |
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Famines occurred in Hong Kong and part of China during the Japanese occupation in World War II. In Hong Kong, the Japanese administration turned the city into a military base and it cut down the rations for civilians to conserve food for soldiers and they also exiled people out of the city.14 Moreover, at that time, many areas in China also experienced famine for various other political reasons. The lack of food, clean water and adequate health care during famine can lead to malnutrition.4 Many studies have demonstrated that malnourished children were prone to develop osteoporosis in their later lives. Dietary calcium, an important nutrient in bone metabolism, plays a major role in the bone accretion in children. Better bone mineral acquisition can be achieved if children can simply drink more milk.15 Adult women who had low milk consumption in childhood were associated with a 2-fold greater risk of fracture.16 In fact, adequate calcium intake in youngsters is a major determining factor in attaining maximum bone mass and prevention of osteoporosis.7 In a randomized controlled trial, pre-pubertal girls were found to have a significantly higher bone mineral content and bigger bone size if they took calcium enriched foods for 1 year.17 Similar results were found in different ethnic groups. In a rural community at the eastern part of South Africa, black children who had low dietary calcium intake were associated with low appendicular bone density.18
Famine results in protein energy malnutrition, leads to growth failure, wasting and stunting.4 Low protein intake can reduce intestinal calcium absorption as the result of secondary hyperparathyroidism.19 In addition, bone re-modelling is reduced, as evidenced by a low serum osteocalcin level which is a bone formation marker, in malnourished children 20 and patients with anorexia nervosa.21
People are usually poorly educated in the region with famine. For example, it has been reported that the adult literacy rate in Niger was only 9% in females and 24% in males, and about 30% of children can enroll in primary school, but only 5% can enrol in secondary school.22 In our study, 88.6% of people who had experienced famine have only primary education level or below. The rate is significantly lower when compared with people who had not experienced famine. In Spain, women with lower social economic status had significantly lower BMD values than those with higher social economic status.23 In the United States, better bone density was found in women with higher education level.24 A recent study in Hong Kong by Ho et al.7 showed that for women, lower educational level was associated with lower BMD by 4.2–11.9% at various sites, and there were 3.5–8.6 times more likely to develop osteoporotic fracture when they were compared with women of high education level.
Birth weight and maternal health status are also important factors in assessing the osteoporosis in later life. Cooper et al.25 have provided direct evidence that a lower growth rate in childhood is associated with hip fracture. Maternal lifestyle, such as smoking, diet (in particular the vitamin D deficiency) and physical activity appears to modulate the bone mineral acquisition during intrauterine life, and low birth size is also positively associated with hip fracture in later life.26,27 It is possible that vitamin D insufficiency in the mother or during childhood contributes to the observed associations28 and that the observed association between bone density and cardiovascular disease stems from a development origin and both disorders. Unfortunately, this information was not available. Hong Kong was a small town 70–80 years ago. It did not have a good surveillance system and a few health data were available. The Hong Kong census in 192129 briefly reported some health information such as the duration of life and birthplace. However, it did not include birth weight and maternal size. Furthermore, people mostly gave birth at home and did not record their birth weights and the maternal sizes.
In our study, we found that subjects who had experienced famine had lower femoral neck BMD and a higher risk of osteoporosis. They tended to have a lower educational level and socioeconomic status, they took less calcium and they engaged in more risky behaviour like smoking. There is increasing evidence that the development of osteoporosis is associated with poor growth and development and adverse early environmental conditions,30 since the skeletal growth is programmed during pre-natal and early post-natal life.31 In our study, all subjects were children six decades ago, who may have experienced famine during the critical period of bone growth. In addition, they also had little educational opportunities. As a result, they may have poor knowledge on bone health and they engage in more risky behaviours. People who had experienced famine suffer from both malnutrition and low education which are related to BMD. Thus, those who had experienced famine are at significantly high risk of developing osteoporosis. The effect of famine is episodic as subjects could resume normal food intake when the episode had passed, whereas the effect of education was lifelong. This may explain why famine became non-significant when the education factor was added into the regression model.
We found that there is an interaction between gender and famine but a similar statistical test for women gave no significant findings in men. We believe that difference in both non-modifiable and modifiable factors may partially explain why famine is associated with osteoporosis in women but not in men. For the non-modifiable factors, men have larger bones and tend to have higher bone density as they age. With reference to the NHANES III,32 the prevalence of osteoporosis in white post-menopausal women was 20% while it was only 4% in men over the age of 50 years. Gender was one of the most important factors controlling bone mass. Women have 5–10% lower bone mass than men do.32 Besides, oestrogen is necessary for normal skeletal maturation and maintenance of bone mass in adult men and women.33 Menopause in women causes rapid decline in oestrogen level where it does not occur in men. In addition, some important modifiable factors between genders are different in our study. Comparing men and women in our study, more men had secondary school-level or above education (39.6 vs 17.3%, P < 0.001); had more dietary calcium intake (628.3 vs 567.9 mg/day, P < 0.001); and men were more physically active (PASE score: 97.3 vs 85.5, P < 0.001) than women. These differences between gender could lower the impact on the significance of famine as a risk factor for osteoporosis in men than in women.
Although our study is cross-sectional, past exposure to famine and educational level are relatively stable characteristics and are unlikely to be influenced by recall bias. We compared the educational level of our subjects to the Hong Kong population. With reference to the Topical Health Report on elderly health prepared by the Hong Kong Government in 2004,34 the percentage of women aged 65 years or above attaining secondary school-level and above is 18.4%, a figure similar to our study population (17.3%). However, definite conclusion regarding a causal relationship between famine and educational level and osteoporosis may not be drawn. Moreover, our study subjects were community-dwelling volunteers and this may create a selection bias. Nevertheless, endemic famine and low education level are still present in many parts of the world. With the prevalence of osteoporosis escalating rapidly, it is an important public health issue that should be tackled promptly.
In conclusion, our findings suggest that among women, past experience of famine, especially during their childhood, is associated with osteoporosis.
| Acknowledgements |
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The study was approved by the Ethics Committee of the Faculty of Medicine, the Chinese University of Hong Kong. This study is partially supported by the Jockey Club Charities Fund.
Conflict of interest: None declared.
KEY MESSAGES
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