a Nelson Institute of Environmental Medicine and Kaplan Comprehensive Cancer Center, New York University School of Medicine, New York 10016, NY, USA.
b Current address: Feist-Weller Cancer Center, Section of Cancer Prevention and Control, LSU Health Science Center, Shreveport, LA 71130, USA.
c Unit of Nutrition and Cancer, International Agency for Research on Cancer, 150 Cours Albert Thomas F-69372, Lyon cedex 08 France.
Reprint requests to: Dr I Kato, Feist-Weller Cancer Center, Section of Cancer Prevention and Control, LSU Health Science Center, 1501 Kings Highway, PO Box 33932, Shreveport, LA 71130, USA.
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Abstract |
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Methods We analysed the relationships of anthropometric, demographic and lifestyle factors with the risk of bone fracture among 6250 postmenopausal women in a prospective cohort study, the New York University Women's Health Study.
Results After an average of 7.6 years of follow-up, 1025 new incident bone fractures were reported, including 34 hip and 159 wrist fractures (incidence rates; 71.6 and 334.7 per 105 woman-years, respectively). The risk of fracture increased with increasing age, body height and total fat intake, while it was significantly lower among obese and African American women. The relative risk among African Americans was 0.45 (95% CI : 0.320.63) compared with non-African Americans. Women taller than 170 cm had a 64% increase in risk of fractures, as compared with those under 155 cm. These associations were generally more pronounced when fractures were limited to those at the hip and wrist.
Conclusions The present study provides an indication for a potential role of dietary fat in the development of postmenopausal fractures and further evidence to support protective effects of obesity, short stature and African American ethnicity.
Keywords Obesity, height, diet, race, postmenopausal bone fracture, prospective study
Accepted 15 July 1999
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Introduction |
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The risk of osteoporotic fractures depends on two ultimate determinants: bone strength and the risk of falling, both of which have been associated with lifestyle, anthropometric and demographic characteristics in various epidemiological and clinical studies.6 These factors may influence the risk of fractures through direct or indirect effects on bone metabolism or by modifying the impact of physical trauma from falls.1,6 For example, dietary intake has direct effects on bone mineral metabolism, while a woman's reproductive history, such as her ages at menarche, menopause and parity, may have an indirect effect by determining her lifetime exposure to ovarian oestrogens. Anthropometric characteristics are also likely to be related to fall impact. Other factors, such as genetic background and cigarette smoking, may influence both hormonal and anthropometric characteristics.
In earlier studies, including several prospective studies,4,5,714 associations with demographic and anthropometric characteristics have been relatively consistent. Larger body mass and African American racial background are the best established protective factors against osteoporotic fractures,4,8,9,11,13,1533 while recent studies have highlighted tall stature as a risk factor for hip fractures.10,14,2226,34 The role of other factors, e.g. dietary intake, cigarette smoking and reproductive history is less clear,1 perhaps because information on these variables is subject to recall bias in case-control studies.
In order to assess prospectively the possible role of a number of risk factors for osteoporotic fractures with various biological mechanisms, we utilized the data from postmenopausal women in the New York University Women's Health Study, a long-term prospective cohort study.
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Methods |
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Among 7839 women who were postmenopausal at baseline (the first examination), 7180 (92%) completed at least one of the follow-up questionnaires which included a question on the occurrence of fracture since age 35. Since the study was a prospective cohort study, we considered fractures reported after the baseline (first) examination as incident cases. Subjects who had postmenopausal fracture before cohort enrolment (n = 773) were excluded together with those with unknown date (n = 157), because their exposure variables, such as nutrient intake, smoking, physical activity and weight, may have changed as a consequence of the fracture. A total of 6250 subjects (80%) remained in the study.
Statistical analysis
We computed each subject's number of person-years at risk as the time from the baseline (first) examination to the date of first postmenopausal fracture, death or last response to a questionnaire, whichever occurred first. We used the Cox proportional hazards model to calculate relative risks (RR) of fracture and their 95% CI. We analysed fractures at all sites as well as fractures at the hip or wrist, the two most common sites for osteoporotic fractures.
We examined dietary intake, smoking, and demographic, anthropometric and reproductive factors at baseline as exposure variables. We used body mass index (BMI = weight [kg]/height [m]2) to assess the degree of obesity (overweight) independent of height. When an exposure variable was continuous, e.g. daily nutritional intake, we computed quintiles based on the frequency distribution of all study subjects. We used the statistical significance of ordered quintile variables to evaluate linear trends using 0, 1, 2, 3 and 4 as the quintile scores. For daily dietary estimates, we calculated calorie-adjusted nutrient intakes using the method proposed by Willett and Stampfer,36 after excluding subjects with missing values for eight or more dietary items.
To select variables to be included in the final multivariate model, the following three factors were considered: (1) magnitude of the association with risk of fracture in age-adjusted analyses (P < 0.05), (2) prior knowledge to justify that a factor is an established risk indicator and magnitude of changes in other risk estimates (more than 10% of the regression coefficients) when included in the model and (3) collinearity between variables as assessed by correlation coefficients. If a correlation coefficient 0.8 was found, only the variable with the strongest association with fracture risk in the age-adjusted model was included, unless the other variable had strong biological basis to account for a causal association. The third component is especially important in diet assessment, as suggested by Elmstahl and Gullberg.37
For most of the covariates studied, missing values represented 6% or lower. Exceptions were 11% and 13% for smoking and ethnicity information, which was collected by a separate questionnaire from the baseline questionnaire. Consequently, when they were included in the multivariate model, indicator variables for the unknown categories were created. The RR for these unknown categories were not significantly different from unity, indicating no substantial biases involved.
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Results |
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Discussion |
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Although no other nutrient intake in adult years has consistently been associated with osteoporotic fractures, our study suggests that fat intake may increase the risk of fracture among postmenopausal women. Diets high in fat and sucrose are known to induce hyperinsulinaemia42 which leads to hypercalciuria, hypermagneciuria, and a negative calcium-magnesium balance. It has also been postulated that a high-lipid diet decreases the efficiency of calcium absorption, since fatty acids form soaps with calcium in the intestine.43 Experiments in ovariectomized rats fed with a high-lipid diet showed a reduced mucosal transference of calcium in all parts of the small intestine.44 In another study, rats fed with a high-fat-sucrose diet had a significantly smaller sixth lumbar vertebra (L6), a smaller cortical shell in the femoral neck (FN) and lower mechanical properties (e.g. load, energy and rigidity) at both L6 and FN than rats fed with a low-fat, complex-carbohydrate diet.45 High dietary fat intake among calorie-restricted animals resulted in lower bone mineral contents at the distal femur.46 In postmenopausal women, total fat intake was shown to be negatively correlated with bone mineral density in the lumbar spine and distal radius.47 In addition, a high fat diet is correlated with dietary intake of retinol, which is known to be a stimulator of bone resorption.48 A recent study from a Scandinavian country demonstrated that dietary retinol intake was negatively associated with bone mineral density and positively associated with risk of hip fracture.49
Although it has been suggested that cigarette smoking results in lower bone mineral density50,51 by reducing cumulative exposure to oestrogens via accelerating natural menopause,52 modifying oestrogen metabolism53 or decreasing body weight,54 the findings on cigarette smoking and risk of osteoporotic fractures have been inconsistent. However, a recent meta-analysis including both cohort and case-control studies suggests that cigarette smoking increases the risk of hip fracture among women aged 60, but not in women <60.55 Although our study did not confirm an association with smoking in the multivariate analysis, the difference may be attributable to the relatively younger age of our study population.
In our data, body height was strongly related to the risk of fractures, especially at the wrist and hip. Case-control studies both in women22,23 and in men24 have found that cases with hip fractures were taller than matched controls. Prospective studies among US registered nurses10 and male health professionals34 reported a doubling of the risk of hip fractures among the tallest group, as compared to the shortest. Very similar results to ours (RR = 3.71) were reported in a cohort of 50 000 Norwegians, in which the RR for hip fractures was 3.62 among women taller than 170 cm, as compared to those under 155 cm.25 The risk of fatal hip fractures was also positively correlated with body height in the Norwegian cohort26 and the incidence of hip fracture was higher among women who were tall at age 25 in a white US cohort.14 Body height is an important determinant of the length of the hip axis, which is positively associated with the risk of hip fracture.56 In addition, fall height increases with increasing body height, resulting in greater potential energy associated with falls.57,58
The inverse association of relative body weight with risk of hip fracture is a consistent observation in both case-control2224,2733 and prospective cohort studies.4,8,9,11,13,25,26 Body mass reflects both fat and fat-free (muscle and bone) masses and both have been positively associated with bone mineral density.19,59 Muscle as well as adipose tissue increases total body weight thus increasing the weight-bearing stress on bone that may stimulate bone remodelling and preserve bone minerals.60 While fat and muscle are a major source of oestrogens in postmenopausal women through the peripheral aromatization of precursor androgens,61 they also provide a cushion during a fall. Among elderly fallers, the risk of fracture has been reported to be lower in those with a larger body mass.57,58
Our observations that the risk of fractures is about half as high in African Americans as in Caucasians is also in agreement with observations that age-specific incidence rates of hip or osteoporotic fractures in black women are about half as high in white women.1517
A limitation of the present study is the potential for misclassification of the outcome of interest as well as mis-classification of other risk factors due to measurement error in the questionnaires. Although it has been reported that the accuracy of self-reported fractures is excellent,62 and although our study subjects were a relatively well-educated population, misclassification of other orthopaedic conditions as fractures is still possible. On the other hand, asymptomatic osteoporotic fractures, such as those common at the vertebrae, may not have been reported.1 These misclassifications may have resulted in biased RR estimates. However, the magnitude of such misclassification is likely to be small because the incidence of total fracture in our cohort, 2.16 per 100 person-year, is within the range of the incidence previously reported for women in similar age groups,17,6265 We also acknowledge some degree of misclassification in fracture sites, although our results for the wrist and hip, which characterized osteoporotic fractures more clearly, generally support the validity of the classification.
A further problem with our study concerns the limited information on physical activity, which has been shown to have a protective effect in other studies.13,14,24,28,31,32,66,67 An indirect measure of physical activity in our study, total calorie intake, did not show any association with risk of fractures. Adequate adjustment for more direct physical activity measurements may have altered the risk estimates to some extent. Furthermore, it should be noted that our questionnaire did not cover the circumstances in which fractures occurred, so that we were unable to exclude high trauma fractures commonly associated with vigorous physical activity or motor accidents, which would bear little relation to osteoporosis.
Selection bias may also be a critical factor in this study. First, our study subjects were participants in mammographic examination, were relatively well educated and were mostly Caucasian, so they did not represent a random sample of the general population. Participants in cancer screening tests are likely to be more health conscious than the rest of the population, as has been observed in other studies.68,69 Second, women who returned the follow-up questionnaires were also self-selected. Therefore, caution needs to be exercised in generalizing the results. In addition, because women who did not respond are more likely to be ill or deceased (possibly from hip fractures) and because of the exclusion of women who had prior postmenopausal fractures, the incidence rate of fractures may be underestimated.
Despite the limitations discussed above, the present study provides an indication that a diet rich in fat may moderately increase the risk of fractures in postmenopausal women, while offering further evidence that obesity, short stature and African American ethnicity are protective.
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Acknowledgments |
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References |
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2 NIH, Office of Medical Applications of Research. Osteoporosis: Consensus Conference. JAMA 1984;252:799802.[ISI][Medline]
3 Cummings SR, Black DM, Rubin SM. Lifetime risk of hip, Colles', or vertebral fracture and coronary heart disease among white postmenopausal women. Arch Intern Med 1989;149:244548.[Abstract]
4 Hemenway D, Colditz GA, Willett WC, Stampfer MJ, Speizer FE. Fractures and lifestyle: effect of cigarette smoking, alcohol intake, and relative weight on the risk of hip and forearm fractures in middle-aged women. Am J Public Health 1988;78:155458.[Abstract]
5 Feskanich D, Willett WC, Stampfer MJ, Graham A, Colditz GA. Milk, dietary calcium, and bone fractures in women: a 12-year prospective study. Am J Public Health 1997;87:99297.[Abstract]
6 Lauritzen JB. Hip fractures: epidemiology, risk factors, falls, energy absorption, hip protectors, and prevention. Danish Med Bull 1997; 44:15568.[ISI][Medline]
7 Kiel DP, Baron JA, Anderson JJ, Hannan MT, Felson DT. Smoking eliminates the protective effect of oral estrogens on the risk of hip fracture among women. Ann Intern Med 1992;116:71621.[ISI][Medline]
8 Kiel DP, Felson DT, Anderson JJ, Wilson PWF, Moskowitz MA. Hip fracture and the use of estrogens in postmenopausal women; the Framingham Study. N Engl J Med 1987;317:116974.[Abstract]
9 Holbrook TL, Barrett-Connor E, Wingard DL. Dietary calcium and risk of hip fracture: 14-year prospective population study. Lancet 1988; ii:104649.
10 Hemenway D, Feskanich D, Colditz GA. Body height and hip fracture: a cohort study of 90 000 women. Int J Epidemiol 1995; 24:78386.[Abstract]
11 Farmer ME, Harris T, Madans HJ, Wallace RB, Cornoni-Huntley J, White LR. Anthropometric indicators and hip fracture. The NHANES I Epidemiologic Follow-up Study. J Am Geriatr Soc 1989;37:916.[ISI][Medline]
12 Looker AC, Harris TB, Madans JH, Sempos CT. Dietary calcium and hip fracture risk: the NHANES I Epidemiologic Follow-up Study. Osteoporosis Int 1993;3:17784.[ISI][Medline]
13 Paganini-Hill A, Chao A, Ross RK, Henderson BE. Exercise and other factors in the prevention of hip fracture: the Leisure World Study. Epidemiology 1991;2:1625.[Medline]
14
Cummings SR, Nevitt MC, Browner WS et al. Risk factors of hip fracture in women. N Engl J Med 1995;332:76773.
15 Farmer ME, White RL, Brody JA, Bailey KR. Race and sex differences in hip fracture incidence. Am J Public Health 1984;74:137480.[Abstract]
16 Bauer RL. Ethnic differences in hip fracture: a reduced incidence in Mexican Americans. Am J Epidemiol 1988;127:14549.[Abstract]
17 Griffin MR, Ray WA, Fought RL, Melton J III. Black-white differences in fracture rates. Am J Epidemiol 1992;136:137885.[Abstract]
18 Cauley JA, Gutai JP, Kuller LH, Scott J, Nevitt MC. Black-white differences in serum sex hormone and bone mineral density. Am J Epidemiol 1994;139:103546.[Abstract]
19 Perry HM III, Horowitz M, Morley JE et al. Aging and bone metabolism in African American and Caucasian women. J Clin Endocrinol Metab 1996;81:110817.[Abstract]
20 Li J-Y, Specker BL, Ho ML, Tsang RC. Bone mineral content in black and white children 1 to 6 years of age. Early appearance of race and sex differences. Am J Dis Child 1989;143:134649.[Abstract]
21 Gilsanz V, Roe TF, Mora S, Costin G, Goodman WG. Changes in vertebral bone density in black girls and white girls during childhood and puberty. N Engl J Med 1991;325:1597600.[Abstract]
22 Kreiger N, Kelsey JL, Holford TR, O'Connor T. An epidemiologic study of hip fracture in postmenopausal women. Am J Epidemiol 1982;116: 14148.[Abstract]
23 Michaëlsson K, Holmberg L, Mallmin H et al. Diet and hip fracture risk: a case-control study. Int J Epidemiol 1995;24:77182.[Abstract]
24 Grisso JA, Kelsey J, O'Brien LA et al. Risk factors for hip fracture in men. Am J Epidemiol 1997;145:78693.[Abstract]
25 Meyer HE, Tverdal A, Falch JA. Risk factors for hip fracture in middle-aged Norwegian women and men. Am J Epidemiol 1993;137:120311.[Abstract]
26 Meyer HE, Tverdal A, Falch JA. Body height, body mass index, and fatal hip fractures: 16 years' follow-up of 674 000 Norwegian women and men. Epidemiology 1995;6:299305.[ISI][Medline]
27 Kreiger N, Gross A, Hunter G. Dietary factors and fracture in postmenopausal women: a case-control study. Int J Epidemiol 1992;21: 95358.[Abstract]
28 Nieves JW, Grisso JA, Kelsey JL. A case-control study of hip fracture: evaluation of selected dietary variables and teenage physical activity. Osteoporosis Int 1992;2:12227.[ISI][Medline]
29
Grisso JA, Kelsey JL, Strom BL et al. Risk factors for hip fracture in black women. N Engl J Med 1994;330:155559.
30 La Vecchia C, Negri E, Vevi F, Baron JA. Cigarette smoking, body mass and other risk factors for fractures of the hip in women. Int J Epidemiol 1991;20:67177.[Abstract]
31 Cooper C, Barker DJP, Wickham CA. Physical activity, muscle strength and calcium intake in fracture of the proximal femur in Britain. Br Med J 1988;297:144346.[ISI][Medline]
32 Wickham CAC, Walsh K, Cooper C et al. Dietary calcium, physical activity, and risk of hip fracture: a prospective study. Br Med J 1989; 299:88992.[ISI][Medline]
33 Cumming RG, Klineberg RJ. Case-control study of risk factors of hip fractures in the elderly. Am J Epidemiol 1994;139:492503.
34 Hemenway D, Azrael DR, Rimm EB, Feskanich D, Willett WC. Risk factor for hip fracture in US men aged 40 through 75 years. Am J Public Health 1994;84:184345.[Abstract]
35 Toniolo PG, Pasternack BS, Shore RE et al. Endogenous hormones and breast cancer: a prospective study. Breast Cancer Res Treat 1991;18: S2326.[ISI][Medline]
36 Willett W, Stampfer MJ. Total energy intake: implications for epidemiologic analyses. Am J Epidemiol 1986;124:1727.[Abstract]
37 Elmstahl S, Gullberg B. Bias in diet assessment methodsconsequences of collinearity and measurement errors on power and observed relative risks. Int J Epidemiol 1997;26:107179.[Abstract]
38 Dawson-Hughes B, Dallal GE, Krall EA, Sadowski L, Sahyoun N, Tannenbaum S. A controlled trial of the effect of calcium supplementation on bone density in postmenopausal women. N Engl J Med 1990;323:87883.[Abstract]
39
Dawson-Hughes B, Harris SS, Krall EA, Dallal G. Effect of calcium and vitamin D supplementation on bone density in men and women 65 years of age or older. N Engl J Med 1997;337:67076.
40 Chapuy MC, Arlot ME, Doboeuf F et al. Vitamin D3 and calcium to prevent hip fracture in elderly women. N Engl J Med 1992;327: 163742.[Abstract]
41
Owusu W, Willett WC, Feskanich D, Ascherio A, Spiegelman D, Colditz GA. Calcium intake and the incidence of forearm and hip fractures among men. J Nutr 1997;127:178287.
42 Barnard RJ, Faria DJ, Menges JE, Martin DA. Effects of a high-fat, sucrose diet on serum insulin and related atherosclerotic risk factors in rats. Atherosclerosis 1993;100:22936.[ISI][Medline]
43 Atteh JO, Leeson S. Effects of dietary saturated or unsaturated fatty acids and calcium levels on performance and mineral metabolism of broiler chicks. Poultry Sci 1984;63:225260.[ISI][Medline]
44 Chanda S, Islam MN, Pramanik P, Mitra C. High-lipid diet intake is a possible predisposing factor in the development of hypogonadal osteoporosis. Jpn J Physiol 1996;46:38388.[ISI][Medline]
45 Zernicke PF, Salem GJ, Barnard RJ, Schramm E. Long-term, high-fat-sucrose diet alters rat femoral neck and vertebral morphology, bone mineral content, and mechanical properties. Bone 1995;16:2531.[ISI][Medline]
46 Sanderson JP, Binkley N, Roecker EB et al. Influence of fat intake and caloric restriction on bone in aging male rats. J Gerontol 1997; 52A:B2025.[ISI]
47 Cooper C, Atkinson EJ, Hensrud DD et al. Dietary protein intake and bone mass in women. Calcif Tissue Int 1996;58:32025.[ISI][Medline]
48 Kindmark A, Melhus H, Ljunghall S, Lijunggren O. Inhibitory effects of 9-cis and all-trans retinoic acid on 1,25(OH)2 vitamin D3-induced bone resorption. Calcif Tissue Int 1995;57:24244.[ISI][Medline]
49
Melhus H, Michaelsson K, Kindmark A et al. Excessive dietary intake of vitamin A is associated with reduced bone mineral density and increased risk for hip fracture. Ann Intern Med 1998;129:77078.
50 Egger P, Duggleby S, Hobbs R, Fall C, Cooper C. Cigarette smoking and bone mineral density in the elderly. J Epidemiol Community Health 1996;50:4750.[Abstract]
51
Bauer DC, Browner WS, Cauley JA et al. Factors associated with appendicular bone mass in older women. Ann Intern Med 1993;118:65765.
52 Kato I, Tominaga S, Sizuki T. Factors related to late menopause and early menarche as risk factors for breast cancer. Jpn J Cancer Res 1988; 79:16572.[ISI][Medline]
53 Michnovicz JJ, Hershcopf, RJ, Naganuma H, Bradlow HL, Fishman J. Increased 2-hydroxylation of estradiol as a possible mechanism for rge anti-estrogenic effect of cigarette smoking. N Engl J Med 1986;315: 130509.[Abstract]
54 Kato I, Tominaga S, Suzuki T. Characteristics of past smokers. Int J Epidemiol 1989;18:34553.[Abstract]
55
Law MR, Hackshaw AK. A meta-analysis of cigarette smoking, bone mineral density and risk of hip fracture: recognition of a major effect. Br Med J 1997;315:84146.
56 Faulkner KG, Cummings SR, Black D, Pelermo L, Gluer CC, Genant HK. Simple measurement of femoral geometry predicts hip fracturethe study of osteoporotic fractures. J Bone Miner Res 1993;8:121117.[ISI][Medline]
57 Hayes WC, Myers ER, Morris JN, Gerhart TN, Yett HS, Lipsitz LA. Impact of near the hip dominates fracture risk in elderly nursing home residents who fall. Calcif Tissue Int 1993;52:19298.[ISI][Medline]
58 Greenspan SL, Myers ER, Maitland LA, Resnick NM, Hayes WC. Fall severity and bone mineral density as risk factors for hip fracture in ambulatory elderly. JAMA 1994;271:12833.[Abstract]
59 Baumgartner RN, Stauber PM, Koehler KM, Romero L, Garry PJ. Associations of fat and muscle masses with bone mineral in elderly men and women. Am J Clin Nutr 1996;63:36572.[Abstract]
60 Schulteis L. The mechanical control system of bone in weightless spaceflight and in aging. Exp Gerontol 1991;26:20314.[ISI][Medline]
61 Longcope C, Pratt JH, Schneider SH, Fineberg SE. Aromatization of endogenous androgens by muscle and adipose tissue. J Clin Endocrinol Metab 1978;46:14652.[Abstract]
62 Sahlin Y. Occurrence of fractures in a defined population: a 1-year study. Injury 1990;21:15860.[ISI][Medline]
63 Donaldson LJ, Cook A, Thomson RG. Incidence of fractures in a geographically defined population. J Epidemiol Community Health 1990; 44:24145.[Abstract]
64 Fife D, Barancik JI. Northern Ohio Trauma Study III: incidence of fractures. Ann Emerg Med 1985;14:24448.[ISI][Medline]
65 Garraway WM, Stauffer RN, Kurland LT, O'Fallon WM. Limb fractures in a defined population. I. Frequency and distribution. Mayo Clinic Proc 1979;54:70107.[ISI][Medline]
66 Coupland C, Wood D, Cooper C. Physical inactivity is an independent risk factor for hip fracture in the elderly. J Epidemiol Community Health 1993;47:44143.[Abstract]
67 O'Neil TW, Marsden D. Adams JE, Silman AJ. Risk factors, falls and fracture of the distal forearm in Manchester, UK. J Epidemiol Community Health 1996;50:28892.[Abstract]
68 Kato I, Tominaga S, Naruhashi H. Characteristics of the participants of stomach cancer screening test. Jpn J Public Health 1986;33: 74953.
69 Kato I, Tominaga S, Matsuoka I. Characteristics of participants of uterine cancer screening test. Jpn J Public Health 1987;34: 74854.