Higher Bone Mineral Density in Rural Compared with Urban Dwellers
The NOREPOS Study
H. E. Meyer1,2 ,
G. K. R. Berntsen3,
A. J. Søgaard1,
A. Langhammer4,
B. Schei4,
V. Fønnebø3,
S. Forsmo4,
G. S. Tell5 and
the Norwegian Epidemiological Osteoporosis Studies (NOREPOS) Research Group
1 Division of Epidemiology, Norwegian Institute of Public Health, Oslo, Norway.
2 Section for Preventive Medicine and Epidemiology, University of Oslo, Oslo, Norway.
3 Institute of Community Medicine, University of Tromsø, Tromsø, Norway.
4 Department of Public Health and General Practice, Norwegian University of Science and Technology, Trondheim, Norway.
5 Department of Public Health and Primary Health Care, University of Bergen, Bergen, Norway.
Received for publication March 5, 2004; accepted for publication July 7, 2004.
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ABSTRACT
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Norway has a very high incidence of osteoporotic fractures, with substantial regional differences in fracture incidence. The present study evaluated whether there are differences in bone mineral density (BMD) between regions in Norway with differences in fracture incidence. The authors used data collected in four large, population-based, multipurpose studies performed in four regions of Norway during 19942001. Distal forearm BMD was measured by single energy x-ray absorptiometry in 10,667 participants aged 4075 years. Cross-calibration was performed by using the European Forearm Phantom. Mean distal forearm BMD was lower in the urban populations of Tromsø, Oslo, and Bergen compared with the rural county of Nord-Trøndelag, whereas there was no difference between the rural part of Tromsø and Nord-Trøndelag. For women, body mass index explained some of these differences. The prevalence of low BMD (z score
1) in Oslo, Bergen, and urban Tromsø, compared with Nord-Trøndelag, was 1.61.7 times higher in men and 1.52.0 times higher in women, whereas no significant difference was found between rural Tromsø and Nord-Trøndelag. In this study, higher BMD was found in rural compared with urban areas of Norway, which might help explain the differences in fracture incidence. There was no apparent north-south gradient in BMD.
bone density; cross-sectional studies; densitometry; forearm; fractures; men; osteoporosis; women
Abbreviations:
Abbreviations: BMD, bone mineral density; CI, confidence interval.
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INTRODUCTION
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The incidence of osteoporotic fractures in the Norwegian population is among the highest ever reported (13). In addition, considerable regional differences in fracture incidence are found inside Norway (46). For example, the incidence of hip fracture has been reported to be about 50 percent higher in the city of Oslo compared with the rural counties of Sogn og Fjordane (6) and Nord-Trøndelag. In the urban populations of Oslo and Bergen, similar rates of forearm fractures have been reported (2, 3). Data from Tromsø suggest a lower incidence of fracture in this urban population (7, 8).
Bone mineral density (BMD) is an important and measurable risk factor for osteoporotic fractures. One standard deviation decrease in BMD at the distal or proximal forearm has been associated with a 7080 percent higher risk of forearm fracture, an 80110 percent higher risk of hip fracture, and a 4050 percent higher risk of fracture at any site (9). Population-based studies comparing cross-calibrated bone densities across different populations are rare (10). In Norway, no population-based study has explored whether there are regional differences in BMD. The purpose of the present study was to evaluate whether there are differences in BMD among four geographic regions of Norway. The regions include urban and rural populations and are situated at different latitudes (from 60°N to 69°N). The latter might be of importance because of differences in sun exposure and the cutaneous production of vitamin D (11).
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MATERIALS AND METHODS
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Subjects
We used data collected in four large, population-based, multipurpose health studies in the cities of Oslo (the Oslo Health Study (HUBRO), 20002001) and Bergen (the Hordaland Health Study (HUSK), 19981999) in southern Norway and Tromsø (the Tromsø Study, 19941995) in northern Norway, and in the rural county of Nord-Trøndelag (the Nord-Trøndelag Health Study (HUNT), 19951997) in middle Norway (figure 1). All studies were part of the CONOR collaborative study (COhort of NORway), a large epidemiologic study with the goal of establishing a cohort of 200,000 adults. The CONOR protocol includes a common set of questions, anthropometric measurements, and some biologic measurements. BMD measurements were included in ancillary studies, forming the Norwegian Epidemiological Osteoporosis Studies (NOREPOS).

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FIGURE 1. Map of Norway showing the geographic location of the study populations in the Norwegian Epidemiological Osteoporosis Studies, 19942001.
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Whereas the studies in Tromsø (12) and Nord-Trøndelag included samples of all adults, the Bergen study included only those aged 4849 and 7274 years and the Oslo study only those aged 30, 40, 45, 60, and 75 years. The present analysis encompassed participants aged 4075 years. In Oslo, with a considerable immigrant population, all participants not born in Norway were excluded from the present analysis. The attendance rate was highest in Tromsø (80 percent, n = 7,394), followed by Nord-Trøndelag (70 percent, n = 1,773) and Bergen (59 percent, n = 207). In the Oslo study, 49 percent (n = 1,584) of the invited persons selected for bone densitometry attended the health screening. However, some went to the screening when the densitometer was not available, and only 40 percent (n = 1,293) of those invited were actually measured. However, no difference was found in body mass index, smoking habits, or education between the participants measured and those not measured for BMD (data not shown). The municipality of Tromsø (61,000 inhabitants) encompasses a large geographic area (2,558 km2). Although the majority of the participants lived in the city center, 19 percent were living in areas defined as rural. The Tromsø sample was therefore subdivided into two groups, urban and rural Tromsø, based on the population density of the election district in which the participants were living.
BMD measurements
Forearm BMD was measured by single energy x-ray absorptiometry; a similar protocol was followed at all study sites (12). One of the authors (G. B.) conducted the basic training at each study site. Five different densitometers were used, all of the same type (DTX-100; Osteometer MediTech Inc., Hawthorne, California). As explained in detail elsewhere (12), bone densitometry was performed at the distal (1020 percent trabecular bone) and ultradistal (5070 percent trabecular bone) forearm sites. Because it has been previously shown that a prior forearm fracture increases BMD (because of callus formation) at the ultradistal but not the distal site (13), and because we did not have comparable data on previous forearm fractures from all substudies, data from only the distal site were included in the present study. Bone densitometry was performed on the nondominant forearm except in 12.5 percent of the cases. We have previously shown that distal forearm BMD is modestly 0.004 g/cm2 higher at the dominant compared with the nondominant side and therefore did not adjust for this factor here (13). Daily calibration was performed with a phantom provided by the manufacturer. All scans were reviewed and reanalyzed if necessary (14). Scans that had serious movement artifacts, did not include the region of interest, contained metallic objects in the region of interest, or were of poor quality because of other causes were excluded (129 in Tromsø, three in Oslo, one in Bergen, and 22 in Nord-Trøndelag).
Cross-calibration was performed by using the European Forearm Phantom (QRM GmbH, Moehrendorf, Germany), which has three hydroxyapatite bone imitations with different densities within the human range. With each densitometer, at each study site, a minimum of 22 scans of the European Forearm Phantom were performed. All of these scans were analyzed by the same two persons according to a strict protocol using the special calculation option in the densitometers software. For each densitometer, the relation between measured BMD and true BMD (supplied by the producer of the European Forearm Phantom) was calculated by linear regression. For all study participants, measured BMD was recalculated to the European Forearm Phantom scale following the equation calculated for the densitometer, and all BMD data in this paper are presented in this scale. On the other hand, the differences between the densitometers before adjustment were modest (maximum 3 percent), and analyzing the unadjusted data gave conclusions similar to those using the recalculated ones (data not shown).
Covariates
Information on covariates was collected similarly for all study populations. Body mass index was calculated as weight divided by height squared from measured weights and heights. Smoking was classified as current smokers or not. Physical activity was assessed by two questions (hours per week of light exercise and hours per week of hard physical activity, both with four alternatives graded from 0 to
3 hours).
Statistics
Adjusted BMD and body mass index were compared between the study sites by using linear regression (ordinary least squares). To estimate the impact that differences in mean BMD might have on differences in fracture incidence, we used results from a meta-analysis of women (9). This meta-analysis presents the relative risk of fracture per standard deviation decrease in BMD. We log-transformed these relative risks, multiplied them (i.e., the ß) by the regional differences in BMD (in standard deviations), and recalculated the relative risks. Because a similar analysis of men is lacking, we used the same results to estimate the impact for men. In an alternative approach to studying the differences in BMD between the regions, we calculated the prevalence and prevalence ratio (the prevalence at each of the other study sites divided by the prevalence in Nord-Trøndelag) of having a low BMD for age, defined as a BMD of one standard deviation or more under the age- and sex-specific mean (z score
1) in the populations. To calculate z scores, we performed sex-specific (but not study-site-specific) linear regressions on BMD by age, and the standard deviation around the estimated regression line was calculated as the root mean square error (15). As standard deviation increased by age, these regression analyses were performed stratified on age (4049, 5061, 6275 years). For the individual participant, a z score was then calculated (measured value minus calculated mean value from the regression above divided by sex- and age-group-specific standard deviation). In addition, for each participant, we calculated a t score (measured BMD minus mean young adult BMD divided by the standard deviation of young-adult BMD). These calculations were performed separately for men and women. Logistic regression was used to calculate the age-adjusted odds ratio of having osteoporosis (t score
2.5 standard deviation).
Ethics
Written informed consent was collected from the par-ticipants. In addition, the individual studies were evaluated by the appropriate Regional Committee for Medical Research Ethics and were approved by the Norwegian Data Inspectorate.
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RESULTS
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In all age groups, distal forearm BMD was higher in men from Nord-Trøndelag compared with men from urban Tromsø, Oslo, and Bergen (figure 2; table 1). Women from Nord-Trøndelag had a higher mean BMD than women from Oslo, Bergen, and urban Tromsø. However, in the oldest subjects, this difference was no longer evident. Furthermore, men and women in most age groups in rural Tromsø had a higher BMD compared with their counterparts in the urban populations (table 1). For both men and women, mean age-adjusted distal BMD was higher in Nord-Trøndelag compared with the urban populations of Oslo, Bergen, and Tromsø (figure 3; table 2). In contrast, there were no significant differences in mean distal BMD between rural Tromsø and Nord-Trøndelag, whereas there were between rural and urban Tromsø.

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FIGURE 2. Age-specific distal bone mineral density (BMD) in men and women in different regions of Norway, the Norwegian Epidemiological Osteoporosis Studies, 19942001.
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TABLE 1. Mean distal forearm BMD* (g/cm2) in four regions of Norway by age and sex, the Norwegian Epidemiological Osteoporosis Studies, 19942001
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FIGURE 3. Distal bone mineral density (BMD) in men (top) and women (bottom) in different regions of Norway, the Norwegian Epidemiological Osteoporosis Studies, 19942001. Shown are age-adjusted means (white bars) with 95% confidence intervals (vertical lines) (evaluated at age 59.7 years in men and 59.5 years in women in a multiple linear regression analysis).
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TABLE 2. Age- and multivariate-adjusted differences in BMD* (g/cm2) between Nord-Trøndelag and the other study regions in Norway, the Norwegian Epidemiological Osteoporosis Studies, 19942001
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In women, mean age-adjusted body mass index was higher in both Nord-Trøndelag (27.0 kg/m2) and rural Tromsø (27.3 kg/m2) than in urban Tromsø (25.6 kg/m2), Oslo (25.3 kg/m2), and Bergen (25.6 kg/m2), corresponding to a 1.58-kg/m2 (95 percent confidence interval (CI): 1.34, 1.83) higher body mass index in the combined rural populations compared with the combined urban populations. The corresponding difference in men was a modest 0.26 kg/m2 (95 percent CI: 0.05, 0.47). For an increase of 5 kg/m2 in body mass index, BMD increased by 0.017 g/cm2 (95 percent CI: 0.014, 0.019) in men and 0.014 g/cm2 (95 percent CI: 0.013, 0.016) in women. When we adjusted for body mass index, BMD differences between the urban and rural populations of women were attenuated, whereas the estimates for men were mostly unaffected (table 2). In men, current smokers had a BMD 0.015 g/cm2 (95 percent CI: 0.011, 0.019) lower than that in nonsmokers; the corresponding figure for women was 0.012 g/cm2 (95 percent CI: 0.008, 0.015). However, further adjustment of regional BMD for smoking did not change the estimates substantially (table 2). Regarding the assessment of physical activity, some data were missing, especially for hard physical activity. However, for those answering the questions, adjustment for physical activity did not change the geographic BMD differences (data not shown).
The prevalence of low BMD (distal forearm BMD z score
1) in Oslo, Bergen, and urban Tromsø was 1.61.7 times higher in men and 1.52.0 times higher in women compared with that in Nord-Trøndelag, whereas there was no significant difference between rural Tromsø and Nord-Trøndelag (table 3). Compared with men in rural Tromsø, men in urban Tromsø had a 1.36 times higher prevalence (95 percent CI: 1.09, 1.68) of low BMD. The corresponding figure for women was 1.37 (95 percent CI: 1.11, 1.68).
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TABLE 3. Prevalence and prevalence ratio of having a distal forearm BMD* z score of 1, the Norwegian Epidemiological Osteoporosis Studies, 19942001
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In an additional analysis, the age-adjusted odds ratio of having osteoporosis (t score
2.5 standard deviation) for the combined urban populations (urban Tromsø, Oslo, and Bergen) compared with the combined rural populations (Nord-Trøndelag and rural Tromsø) was 1.37 (95 percent CI: 1.11, 1.69) for men and 1.52 (95 percent CI: 1.29, 1.79) for women.
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DISCUSSION
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In this study, we found differences in BMD between regions of Norway. The BMD difference among the three Norwegian cities included and the rural county of Nord-Trøndelag (and rural Tromsø) corresponds to a one-fourth to one-third standard deviation or an estimated 1520 percent higher risk of forearm fracture and an 1825 percent higher risk of hip fracture in men. For women, the difference corresponds to a one-fifth to one-fourth standard deviation or an estimated 1215 percent higher risk of forearm fracture and a 1418 percent higher risk of hip fracture. A higher body mass index in the rural areas could explain some of the urban/rural BMD difference in women, but not in men.
This population-based study is one of the first demonstrating differences in BMD between populations with different fracture risks. In connection with the European Vertebral Osteoporosis Study, bone densitometry with dual energy x-ray absorptiometry in 16 European populations with a great variation in fracture risk showed that considerable differences in BMD exist across Europe, with the Scandinavian centers of Malmö (Sweden) and Oslo in the group with the lowest BMD (10). Although there are limited data comparing validated fracture incidence in different regions of Norway, our BMD findings are in accordance with a high fracture incidence in Oslo and Bergen and a lower incidence in Nord-Trøndelag, but they can probably not explain the whole difference. Available data suggest a lower incidence of fracture in Tromsø compared with Oslo (7, 8). BMD was similar in Oslo and urban Tromsø (although mean BMD tended to be lower in men in Oslo), which might indicate a higher prevalence of other risk factors for fracture than BMD in Oslo.
Nord-Trøndelag is generally a rural county including a few small towns. We found a corresponding difference in BMD between rural and urban Tromsø as between Nord-Trøndelag and the three cities. There was also an urban/rural difference in the prevalence of osteoporosis (t score
2.5 standard deviation), lending further support to an urban/rural difference in fracture incidence. An urban/rural difference in bone content/density has previously been described in Sweden (16, 17), and several studies have reported higher fracture rates in urban compared with rural areas, in both Norway (46) and other Western countries (1821). Low body mass index is an established risk factor for osteoporosis (22). In our study, women, but not men, in the urban areas had a lower body mass index compared with their counterparts in the rural areas, and body mass index could explain some, but not all, of the urban/rural BMD differences. Further adjustment for smoking did not change these estimates. We did not find that physical activity played a role in explaining the differences in BMD. However, in light of the broad estimates of physical activity levels and the missing data in this study, we cannot exclude the possibility that physical activity does play a role.
There was no apparent north-south gradient in BMD. Nord-Trøndelag is situated in the middle of Norway (64°N), Oslo and Bergen in southern Norway (60°N), and Tromsø in northern Norway (69°N), north of the Arctic Circle (66°N) and with midnight sun during the summer and polar night during NovemberJanuary. However, this factor might be of minor importance because, even in southern Norway, the sun is so low during OctoberApril that cutaneous production of vitamin D is virtually absent (11).
In our study, BMD was measured by using the same type of densitometer (DTX-100), with a similar protocol followed at all study sites. Cross-calibration of all densitometers with the European Forearm Phantom enabled us to recalculate all measurements to the same scale. On the other hand, only modest differences existed between the densitometers before adjustment, and analyses using crude data gave conclusions similar to those obtained when the recalculated ones were used.
A limitation of our study is that BMD was measured at the forearm only. However, the NORA study recently showed that peripheral measurements, including the forearm, have a strong relation to later osteoporotic fracture (23). Forearm single energy x-ray absorptiometry is also one of the most precise bone densitometric methods (24). The substudies were performed over a time span of 6 years, in populations in which the public focus on osteoporosis might have differed. Attendance rates varied between study sites, and selection bias is of concern when comparing these cross-sectional data. On the other hand, we found a similar difference in BMD between urban and rural Tromsø, the substudy with the highest attendance rate (80 percent) as between the rural county of Nord-Trøndelag (70 percent attendance rate) and the urban study sites. In addition, a comprehensive study of the effects of nonattendance in the Oslo Health Study concluded that prevalence estimates of factors associated with BMD such as body mass index and smoking were robust even in light of considerable nonattendance (25).
A previous study found that Oslo, with the highest incidence of osteoporotic fractures ever reported, belonged to the group having the lowest BMD in Europe (10). In the present study, we found that BMD was lower in Oslo and other Norwegian cities compared with rural areas, which might help explain differences in fracture incidence within Norway. For women, some of the differences in BMD could be explained by a higher body mass index in the rural populations. Despite different latitudes between the study sites, no north-south gradient in BMD was observed.
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ACKNOWLEDGMENTS
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The studies were supported by grants from the Norwegian Foundation for Health and Rehabilitation, Norwegian Osteoporosis Foundation, Norwegian Womens Public Health Association, and Research Council of Norway. Economic support was also received from Astra Zeneca Norway; Merck, Sharpe & Dohme Norway; Norwegian Rheumatism Association; and TINE BA (Norwegian Dairy Industry).
In all studies, the data were collected in collaboration with the National Health Screening Service of Norway, now the Norwegian Institute of Public Health.
The NOREPOS Research GroupCore Research Group: Drs. Gro K. R. Berntsen (Tromsø), Haakon E. Meyer (Oslo), Berit Schei (Nord-Trøndelag), and Grethe S. Tell (Bergen). Local Collaborators (regions in alphabetic order): Drs. C. G. Gjesdal, G. S. Tell, and S. Aanderud (Bergen); Drs. L. Forsén, S. Forsmo, Ø. Krüger, A. Langhammer, and B. Schei (Nord-Trøndelag); Drs. J. A. Falch, H. E. Meyer, and A. J. Søgaard (Oslo); and Drs. G. K. R. Berntsen, V. Fønnebø, and R. Joachimsen (Tromsø).
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NOTES
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Correspondence to Dr. Haakon E. Meyer, Norwegian Institute of Public Health, P.O. Box 4404 Nydalen, 0403 Oslo, Norway (e-mail: haakon.meyer{at}fhi.no). 
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