Vitamin D Deficiency and Bone Health in Healthy Adults in Finland: Could This Be a Concern in Other Parts of Europe?

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1 JOURNAL OF BONE AND MINERAL RESEARCH Volume 16, Number 11, American Society for Bone and Mineral Research Vitamin D Deficiency and Bone Health in Healthy Adults in Finland: Could This Be a Concern in Other Parts of Europe? CHRISTEL J.E. LAMBERG-ALLARDT, 1 TERHI A. OUTILA, 1 MERJA U.M. KÄRKKÄINEN, 1 HANNU J. RITA, 2 and LIISA M. VALSTA 3 ABSTRACT A low vitamin D status could be a concern not only in children and the elderly in Europe, but also in adults. We do not know the effect of mild vitamin D deficiency on bone in this age group. The aim of this study was to detect the prevalence of low serum 25-hydroxyvitamin D [S-25(OH)D] and elevated serum intact parathyroid hormone (S-iPTH) concentrations in healthy young adults in the winter in northern Europe and to characterize the determinants of these variables. In addition, we studied the association between vitamin D status and forearm bone mineral density (BMD) in this population group. Three hundred and twenty-eight healthy adults (202 women and 126 men, years) from southern Finland (60 N) participated in this study conducted in February through March Fasting overnight blood samples were collected in the morning. Forearm BMD was measured by dual-energy X-ray absorptiometry (DXA). The mean daily vitamin D intake met the recommendations in the men ( g) and almost met it in the women ( g). The mean S-25(OH)D concentrations did not differ between genders (women, nm; men, nm; mean SD), but the women had significantly higher mean S-iPTH levels than the men (women, ng/liter; men, ng/liter; p < 0.001). Low S-25(OH)D concentrations (<25 nm) were found in 26.2% of the women (53 women) and 28.6% of the men (36 men), respectively. Based on nonlinear regression analysis between S-25(OH)D and S-iPTH concentration, the S-iPTH concentration started to increase with S-25(OH)D concentrations lower than 80 nm in the women and lower than 40 nm in the men. Based on this relation between S-25(OH)D and S-iPTH concentrations, 86% of the women and 56% of the men had an insufficient vitamin D status. In linear regression analysis, the main positive determinants of S-25(OH)D were dietary vitamin D intake (p < 0.02), the use of supplements (p < 0.005), alcohol intake (p < 0.05), and age (p < 0.005). Smoking associated negatively with the S-25(OH)D concentration (p < 0.03). The main determinants of S-iPTH were S-25(OH)D (p < 0.01), dietary calcium intake (p < 0.02), and body mass index (BMI; p < 0.01). In addition, female gender was associated with higher S-iPTH concentration. The mean daily dietary calcium intake was mg and mg, in the men and women, respectively. Significantly lower forearm BMD was found in the men (p 0.01) but not in the women (p 0.14) with higher S-iPTH concentrations. Low vitamin D status was prevalent in these young adults in northern Europe in winter, although the vitamin D intake met the recommendation. This probably is not a local problem for northern Europe, because the natural sources of vitamin D are scarce and fortification is not very common in Europe, and with the exception of the southern part of Europe, sunshine is not very abundant in this part of the world. Thus, the results of this study indicate that more attention should be focused on vitamin D status and the sources of vitamin D in these countries. (J Bone Miner Res 2001;16: ) Key words: vitamin D, parathyroid hormone, bone metabolism, young adults 1 Calcium Research Unit, Department of Applied Chemistry and Microbiology, University of Helsinki, Helsinki, Finland. 2 Department of Ecology and Systematics, Division of Population Biology, University of Helsinki, Helsinki, Finland. 3 Department of Nutrition, National Public Health Institute, Helsinki, Finland. 2066

2 VITAMIN D DEFICIENCY AND BONE IN ADULTS INTRODUCTION MANY STUDIES have shown that at high latitudes, a large percentage of the population groups studied, mainly children and the elderly, are suffering from low vitamin D status during the winter months. (1,2) In the Seneca Study (3) it was shown that low serum 25-hydroxyvitamin D [S-25(OH)D] concentrations were more common in the elderly in the southern European countries than in the northern countries that were included in the study. Decreased bone mineral density (BMD) related to vitamin D deficiency and increased serum parathyroid hormone (S-PTH) concentrations have been reported in the elderly and in middleaged women. (4,5) Earlier studies have revealed that in Finland (situated 60 N and higher) small children, (6) vegans, (7) and especially institutionalized elderly are at risk of vitamin D deficiency. (1) Recently, we have shown a high prevalence of low 25(OH)D concentrations in pubertal girls in southern Finland, which associated with increased S-PTH concentrations. (8) In the European countries, vitamin D deficiency in the adult population could be more prominent than formerly recognized because sun is not very abundant in a large part of Europe during winter and the dietary sources of vitamin D are scarce. In addition, fortification of food with vitamin D is not very common and the legislation differs among the countries. For instance, in Finland only margarine and soft spreads are vitaminized to a level that has an effect on vitamin D intake, whereas in Denmark no foodstuff is vitaminized. In contrast, vitamin D deficiency may not be so common in the United States because fortification with vitamin D is more common than in Europe. Recently, in several studies done mainly among the elderly, attention has been focused on the importance of the association between S-25(OH)D and S-PTH concentration in the definition of vitamin D deficiency. A reevaluation of this definition has been requested because it seems that S-25(OH)D concentrations as high as nm should be needed to achieve a plateau in the S-PTH concentration. (9 12) However, this definition cannot be used in other age groups because S-PTH could be regulated differently at different ages. To prevent fractures later in life, bone loss should be minimized also in adulthood. The prevalence of low vitamin D status in relation to elevated S-PTH status has not been evaluated in young adults in any previous cross-sectional study. Thus, it is important to study the role and associations between vitamin D status and S-PTH concentrations as well as lifestyle factors with calcium and bone metabolism also among young adults and not only in the elderly. In this study, we investigated the prevalence of low S-25(OH)D and increased S-PTH concentrations in healthy young Finnish adults, both females and males, in the winter when vitamin D status is expected to be at its lowest. The association between vitamin D status on BMD was studied, and the various determinants of S-25(OH)D and S-PTH concentrations as well as the predictors of forearm BMD were evaluated in regression models. Subjects MATERIALS AND METHODS The study was conducted in the capital area (Helsinki- Vantaa, 60 N) and Turku-Loimaa area ( 60 N) during February through March The invited subjects had participated in the National FINRISK Study 1997 Survey, organized by the National Public Health Institute in spring 1997 to which the participants were randomly selected. (13) Subjects (age group, years) that had participated in the FINRISK Study (n 877) were invited to this additional study. Of these invited, 40% (n 350) responded and adequate data were obtained from 328 healthy young adults (202 women and 126 men, aged years). Only 6 of the 202 (3.0%) women had no menstruation (in menopause), 4 (2.0%) had irregular cycles, and 55 (27.2%) used estrogen-containing contraceptives. Laboratory measurements Fasting blood samples were taken between 7:30 and 9:15 a.m. Serum samples were stored at 20 C until analyzed. The serum 25(OH)D concentration was measured by a radioimmunoassay (Incstar Corp., Stillwater, MN, USA). The intra- and interassay CVs were 10.1% and 14.9%, respectively. The reference range for 25(OH)D was nm. The serum intact PTH (S-iPTH) concentration was measured using an immunoradiometric method (Nichols Institute, Juan San Capistrano, CA, USA) with ng/ liter as a reference range. Intra- and interassay CVs for ipth were 3.7% and 1%, respectively. Serum calcium (S-Ca) and serum phosphate (S-P) concentrations were measured by routine laboratory methods. Nutrient intakes and other background data The dietary vitamin D and Ca intakes were estimated by semiquantitative food frequency questionnaires (FFQ) previously used in dietary studies. (14) Each FFQ was checked by a nutritionist together with the subject. A questionnaire was used to collect information on weight, height, physical activity, smoking habits, and alcohol consumption of the subjects during the last 2 weeks. The use of supplements and sunlight exposure in sunny places abroad during the last 3 months also was asked. Physical activity was calculated in minutes per day. Measurement of forearm BMD 2067 Distal forearm total BMD (g/cm 2 ) was measured by a PIXI 1.34 portable densitometer with dual-energy X-ray absorptiometry (DXA) technique with 0.4% precision (Lunar Corp., Madison, WI, USA). The quality control of measurements was made daily with a phantom provided by the manufacturer. When analyzing forearm BMD, the women in menopause (6 of 202 women) were excluded from statistical analysis. Additionally, BMD data were missing from 2 of 126 men.

3 2068 LAMBERG-ALLARDT ET AL. TABLE 1. CHARACTERISTICS OF THE STUDY GROUPS (MEAN SD) Variable Females (n 202) Males (n 126) p Value* Age (year) NS Height (cm) Weight (kg) BMI (kg/m 2 ) S-25(OH)D (nmol/liter) NS S-iPTH (ng/liter) S-Ca (mmol/liter) S-P (mmol/liter) NS Dietary intake Vitamin D ( g/day) Ca (mg/day) NS Sampling time (a.m.) NS Exercise (minutes/day) Using vitamin D supplements (%) Smoking (%) cigarettes per day Using alcohol (%) grams per day Having sunlight (%) NS * Based on t-test except for percentages where 2 -test was used. During last 3 months. During last 2 weeks. Statistics The variables were checked for normality and natural logarithm (ln) transformations were used for skewed variables. Differences between genders in background variables (characteristics of the study groups Table 1) were tested using Student s t-test (numerical variables) and 2 test (dichotomic variables). The association between S-25(OH)D and S-iPTH concentrations was studied both by linear and nonlinear regression models. The determinants of S-25(OH)D and S-iPTH concentrations and forearm total BMD were studied also in the regression models. Based on the relation between S-25(OH)D and S-iPTH concentration, the association of S-25(OH)D and S-iPTH with forearm BMD was studied by the Mann-Whitney U test and analysis of covariance (ANCOVA). Statistical analyses were performed using the BMDP software (BMDP Statistical Software, Inc., Los Angeles, CA, USA). (15) RESULTS Serum 25(OH)D and ipth concentrations The women had significantly higher mean S-iPTH concentrations than the men (p 0.000), but the S-25(OH)D concentration did not differ between genders (Table 1). The percentage having S-25(OH)D concentrations lower than 25 nm, which often is used as a cut point value for vitamin D deficiency, were 26.2% in the women (53 women) and 28.6% in the men (36 men), respectively. In linear regression analysis 1 U increase in S-25(OH)D concentration on the ln-scale decreased S-iPTH concentration on the ln-scale by U (p 0.001) in the women and U (p 0.02) in the men. In addition to the linear model, a nonlinear regression model was fitted between the variables. Based on the relationship between S-25(OH)D and S-iPTH concentration, the plateau for S-iPTH concentration was reached at 26 ng/liter in the women [25.5 ng/liter 24.9 ng/liter 22.4 exp( nm)] and 23 ng/liter [22.9 ng/ liter 22.5 ng/liter 32.2 exp( nm)] in the men (Figs. 1A and 1B). As presented in Figs. 1A and 1B, the S-iPTH concentration started to increase with S-25(OH)D concentrations lower than 80 nm in the women and lower than 40 nm in the men, respectively. The S-25(OH)D concentration was lower than 80 nm in 173 (86%) of 202 women, and lower than 40 nm for 71 (56%) of 126 men (Figs. 1A and 1B). Secondary hyperparathyroidism (S-iPTH 65 ng/liter) was found only in 1 woman and in 1 man. S-25(OH)D concentrations higher than the reference limit of 120 nm was found in 15 of 328 subjects (4.6%); 10 of these subjects used vitamin D supplements regularly and 3 recently had been in sunny areas abroad. Variables associated with S-25(OH)D concentration The dietary vitamin D intake met the recommendations (5 g/day) (16) in the men and almost met them in the women (Table 1). To study the determinants of S-25(OH)D concentration, the following variables were used in the regression models: gender, age, body mass index (BMI), use of vitamin D supplements, sunlight exposure, dietary vitamin D intake, exercise, alcohol consumption, and smoking frequency (Table 2). This model explained 13% of the variance on the S-25(OH)D concentration. Dietary vitamin D intake and the use of vitamin D containing supplements as well as

4 VITAMIN D DEFICIENCY AND BONE IN ADULTS 2069 TABLE 2. THE DETERMINANTS OF THE S-25(OH)D CONCENTRATION ANALYZED IN A LINEAR REGRESSION MODEL. S-25(OH)D AND VITAMIN D INTAKE ARE ln-transformed IN THE ANALYSIS Variable p Gender Age (years) BMI (kg/m 2 ) Vitamin D intake ( g/day) Sunshine Supplements Smoking Alcohol Exercise Model r p Gender, 0 male and 1 female; sunshine exposure (during last 3 months), 0 no and 1 yes; use of vitamin D supplements (during last 3 months), 0 no and 1 yes; smoking, 0 no and 1 yes; alcohol, daily intake in 5-g intervals; exercise, daily amount in 20-minute intervals. TABLE 3. THE DETERMINANTS OF THE S-iPTH CONCENTRATION IN A LINEAR REGRESSION MODEL. S-25(OH)D, CA INTAKE, AND S-iPTH ARE ln-transformed IN THE ANALYSIS Variable p FIG. 1. (A) Association between S-25(OH)D and S-iPTH concentrations in nonlinear regression model in the women (n 202) and (B) in the men (n 126). vacationing in a sunny region during the last 3 months were associated positively with the S-25(OH)D concentration. Smoking was associated negatively and alcohol intake positively with the S-25(OH)D concentration. In addition, age was a significant positive determinant of the S-25(OH)D concentration. In an additional univariate analysis we found a significant correlation (p 0.03) between age and traveling to sunny places. Variables associated with serum ipth concentration To study the determinants of S-iPTH concentration, the following variables were used in the regression models: age, BMI, dietary Ca intake, sampling time, S-25(OH)D, S-Ca and S-P concentrations, exercise, alcohol consumption, and smoking frequency (Table 3). This model explained 13% of the variance in the S-iPTH concentration. Ca intake and S-25(OH)D associated negatively with the S-iPTH concentration and the S-Ca concentration tended to do so also. BMI associated positively with the S-iPTH concentration. Sampling time did not associate with the S-iPTH concentration. However, gender was a strong determinant of the S-iPTH concentration, and consequently we performed the same Gender Age (years) BMI (kg/m 2 ) Ca intake (mg/day) S-25(OH)D (nmol/liter) Sampling S-Ca (mmol/liter) S-P (mmol/liter) Smoking Alcohol (5 g/day) Exercise (20 minutes/day) Model r p Gender, 0 male and 1 female; sampling: time in 15-minute intervals between 7:30 and 9:15 a.m.; smoking, 0 no and 1 yes. analysis for the women and men separately. In the females 1-U increase in S-25(OH)D concentration (p 0.001) and 1-U increase in S-Ca concentration on the ln-scale (p 0.08) decreased S-iPTH concentration on the ln-scale by U and U, respectively, whereas dietary Ca intake did not associate with the ipth concentration. However, in the men dietary Ca intake was found to be a stronger determinant of the S-iPTH concentration than any other tested variable, and 1-U increase in daily Ca intake on the ln-scale decreased S-iPTH concentration on the ln-scale by U (p 0.04). In both the women (p 0.02) and the

5 2070 LAMBERG-ALLARDT ET AL. TABLE 4. DETERMINANTS OF FOREARM BMD (g/cm 2 ) IN THE WOMEN AND IN THE MEN ANALYZED WITH A REGRESSION MODEL Women (n 196) Men (n 124) Variable p p S-25(OH)D* (nmol/liter) S-iPTH* (ng/liter) Ca intake* (mg/day) Height (cm) BMI (kg/m 2 ) Age (year) Exercise (every 20 minutes/day) Smoking (yes/no) Alcohol (every 5 g/day) Model r r p p 0.92 * ln-transformed. men (p 0.02) an increase in1uinbmiincreased S-iPTH concentration on the ln-scale by U and U. All variables together explained 14% (p model 0.001) of the variance in the S-iPTH concentration in the women and 14% (p model 0.05) in the men. In addition, in the women, a simple linear regression analysis revealed that the use of estrogen-containing supplements decreased S-iPTH concentration on the ln-scale by U (p 0.04), but the correlation became insignificant (p 0.14) when tested together with other variables. It is noteworthy that the mean dietary Ca intake (Table 1) was practically adequate in both the women and the men, meeting the recommendation of 1000 mg/day. (16) Predictors of forearm BMD In the simple linear regression models, S-25(OH)D or S-iPTH concentrations did not correlate with forearm BMD in either gender (p values ). In the multiple regression models, age, BMI, height, Ca intake, S-25(OH)D and S-iPTH concentrations, smoking frequency, alcohol consumption, and daily exercise were used as independent variables (Table 4). In these regression models the explanation of the variation in forearm was 15% (p model 0.001) in the women and 3% (p model 0.917) in the men. A 1-U increase in BMI significantly increased forearm BMD by U (p 0.001) in the women, and current smoking decreased it by U (p 0.05). Based on the relation between S-25(OH)D and S-iPTH concentrations, the association between low vitamin D or high S-iPTH concentration and forearm BMD were studied in both genders. The mean values of measured BMD did not differ between the groups categorized by a low vitamin D status or a good vitamin D status [S-25(OH)D concentration lower (n 173) or higher (n 23) than 80 nm for women or lower (n 71) or higher (n 53) than 40 nm for men, respectively] in either gender. None of the other variables (age, BMI, PTH, exercise, alcohol intake, or smoking) that were analyzed differed between the groups. Additionally, as the plateau for women was reached at S-25(OH)D concentrations higher than 80 nm, we analyzed the differences in BMD of the women using the S-25(OH)D concentration of 40 nm, which was found in the men as a cut-point value, but the means did not differ significantly between the groups (p values ). When the subjects were divided into women having S-iPTH concentrations higher (n 118, ng/liter) or lower (n 78; 18 6 ng/liter) than the plateau concentration (26 ng/liter) and men having S-iPTH concentrations higher (n 61; ng/liter) or lower (n 63; 14 5 ng/liter) than the plateau (23 ng/liter), significantly lower forearm BMD mean values were found in the men having higher PTH values (0.548 g/cm g/cm 2 and g/cm g/cm 2, respectively; p 0.01). However, in the women the difference in forearm BMD between the groups did not reach significance (0.440 g/cm g/cm 2 and g/cm g/cm 2, respectively; p 0.14). In the women, there was a significant difference (p 0.01) in the S-25(OH)D concentration between the groups, and Ca intake tended to differ (p 0.06), being lower in the group with high ipth concentrations, as it did also in the men (p 0.06).These results indicate that both S-25(OH)D concentration and Ca intake affect S-iPTH concentration. There were no differences in BMI, age, exercise, alcohol consumption, or smoking in either gender between the groups. DISCUSSION In this study we showed that one-third of a young adult Finnish population was vitamin D deficient during winter ( 25 nm). However, based on the relation between S-25(OH)D and S-iPTH concentrations, the situation was even more alarming: 86% of the women and 56% of the men had an insufficient vitamin D status. This study was performed at the end of the winter; when there was no vitamin D synthesis in the skin it was many

6 VITAMIN D DEFICIENCY AND BONE IN ADULTS months since vitamin D was synthesized and stored. Thus, dietary and supplemental vitamin D as well as occasional traveling to sunny places during winter holidays should be of utmost importance in maintaining an appropriate vitamin D status. The mean dietary vitamin D intake practically met recent recommendations (16) in both genders. Of the determinants studied, both dietary vitamin D intake and vitamin D containing supplements associated positively with S-25(OH)D concentration, and traveling to a sunny place tended to do so also. Among the persons having the highest S-25(OH)D concentration, a large part used supplements or had been to some sunny place during the last 3 months. In line with an earlier study, (17) smoking inversely tended to associate with S-25(OH)D concentration in the women. This could be because of the fact that on an average, women smokers used less vitamin D supplements and had a lower dietary vitamin D intake, sunshine exposure during the last 3 months, or summertime outdoor exercise. However, this association also could be caused by the effect of smoking on vitamin D metabolism. In addition, alcohol intake associated positively. The reason for this is obscure, but the alcohol intake was moderate and could reflect some other lifestyle factor. There also was a significant positive association between age and the S-25(OH)D concentration. The reason for this could be that the older persons traveled abroad more than the younger ones. Vitamin D deficiency could lead to secondary hyperparathyroidism. In elderly postmenopausal women seasonal variation in the S-25(OH)D concentration has been associated with seasonal changes seen in S-iPTH concentrations and BMD. (18,19) In this group of healthy adults with adequate mean dietary Ca intake, only 1 of 202 women and 1 of 126 men had S-iPTH higher than the upper reference limit, regardless of the fact that in the subjects with low S-25(OH)D concentrations S-PTH was increased. It is well known that the S-PTH concentration often reaches above the upper reference limit in the elderly, which is in contrast with the results on our young adults, indicating that the regulation of the S-iPTH concentration is better-controlled in younger adults than in the elderly. Recent studies among the elderly have reported that S-25(OH)D concentrations from 30 to 100 nm are needed to keep the S-iPTH concentration at adequate levels. (10,11,18,20) In this study, the results clearly showed that the S-iPTH concentrations started to increase with S-25(OH)D concentrations lower than 80 nm in the women and lower than 40 nm in the men. Thus, our results show that as compared with men, higher S-25(OH)D concentrations are needed to keep S-iPTH concentrations low during winter among healthy young women. This could have deleterious effects especially on the BMD of the women in the end. When talking about the association between S-PTH and S-25(OH)D, it should be remembered that there is no biological evidence that 25(OH)D directly could regulate the synthesis or secretion of PTH in the parathyroid gland. However, the serum concentration of 1,25-dihydroxyvitamin D, the biologically active form of vitamin D, usually is not low in mild vitamin D deficiency and does not correlate with S-PTH concentrations, though it physiologically is an important down-regulator of PTH synthesis. It 2071 also should be remembered that the main regulators of S-PTH are the S-Ca and S-P concentrations, the former decreasing the S-iPTH concentration and the latter increasing it. In addition, other factors such as exercise could affect indirectly the S-iPTH concentration. (21) Thus, we wanted to study the determinants of S-iPTH more closely and to look at the role of S-25(OH)D in a multiple regression analysis. In the whole study group, the main determinants of S-iPTH were S-25(OH)D, dietary Ca intake, gender, and BMI. On an average, the women had significantly higher mean S-iPTH and lower S-Ca concentrations than the men. In the women multiple regression analysis revealed that lower S-25(OH)D predicted higher S-iPTH concentration and lower S-Ca tended to do so also. Interestingly, in the men, dietary Ca intake was a stronger determinant of S-iPTH than any other tested variable. In addition, in both genders higher S-iPTH concentrations were found in subjects with greater BMI. This is in line with the study by Landin-Wilhelmsen and coworkers (22) who reported that BMI correlated positively with S-iPTH concentration in 24- to 64-year-old adults, suggesting that increased musculoskeletal load in subjects with higher BMI could stimulate PTH secretion. Lifestyle factors, including smoking, alcohol consumption, and daily exercise, did not have significant effects on the S-iPTH concentration in either gender. The use of estrogencontaining contraceptives inversely correlated with S-iPTH concentration in the women, but after all other determinants were included in the regression model, the relationship disappeared. Because it has been shown earlier that there is a circadian rhythm in the S-iPTH concentration and a nadir in S-iPTH secretion at 9:30 a.m., (23) we took the fasting blood samples between 7:30 and 9:15 a.m. The results show that this narrow sampling time did not affect the S-iPTH concentration. One aim of this investigation was to study the association between S-25(OH)D as well as S-iPTH concentrations and forearm BMD, including other potential variables in the analysis. Forearm BMD measured with DXA correlates with DXA measurements at other sites (24) and discriminates between osteoporotic and normal women, but measurements at the lumbar spine and femoral neck are superior. (25) The mean forearm BMD measured did not differ significantly among the groups categorized by the serum 25(OH)D concentration, but higher S-iPTH concentrations predicted lower distal forearm BMD in the men and tended to predict it in the women. However, because sex hormones are important regulators of bone metabolism in the adult, the influence of vitamin D deficiency and PTH may be of less importance in this age group than in postmenopausal women and in the elderly. Interestingly, an association between S-PTH concentration and forearm BMD has been reported in patients with celiac disease. (26) The negative effect of smoking on BMD has been reported earlier (27) and also was seen in our study in the women but not in the men, which may be caused by the fact that smoking could affect the estrogen levels. (28) Exercise has been shown previously to affect positively both the growing and the mature skeleton. (29,30) In this study exercise did not associate with forearm BMD in either gender. This could be caused by the site

7 2072 LAMBERG-ALLARDT ET AL. of BMD measurement and the way we have calculated exercise. In conclusion, the results showed that vitamin D deficiency was common in this normal adult population, and that vitamin D status affected the S-iPTH concentration in both men and women but that dietary Ca intake was a more important determinant of S-iPTH than 25(OH)D in the men in regression analysis. In addition, we found that the S-25(OH)D concentration at which S-iPTH reached a plateau differed between the men and women and that there was an association between forearm BMD and S-iPTH concentration but not between forearm BMD and S-25(OH)D. Thus, keeping the S-PTH concentration low, for example, by an optimal vitamin D status, could be of importance for bone health also in this age group. However, the effect of a sufficient vitamin D status on S-PTH concentrations and on bone should be studied in an intervention study also in this age group. Second, although the mean dietary intake of vitamin D met the current recommendation in the men and almost met the recommendation in the women, we found a high prevalence of low S-25(OH)D concentrations at the end of the winter season, which also was reflected in the S-iPTH concentrations. This indicates that even in a normal, healthy adult population the vitamin D stores that have been built up during summer are not enough to guarantee an optimal vitamin D status. However, more importantly, the results show that dietary vitamin D intake that meets the current recommendations is not enough to combat vitamin D deficiency if there is no sunshine. Although this study was performed only in a limited number of persons in two regions in southern Finland, one could presume that this is not only a local problem for Finland but for the whole of northern Europe. The sources of vitamin D are few, fortification of foods with vitamin D in Europe is scarce, and sun is not abundant in a large part of Europe. We strongly recommend that this study should be repeated in other northern European countries. The results of this study also indicate that more attention should be focused on the sources of vitamin D in these countries. ACKNOWLEDGMENTS This work was supported by grants from the Academy of Finland, Sigrid Juselius Foundation, Ministry for Education, and the Liv och Hälsa Foundation. REFERENCES 1. Lamberg-Allardt C 1984 Vitamin D intake, sunlight exposure and 25-hydroxyvitamin D levels in the elderly during one year. Ann Nutr Metab 28: Webb AR, Pilbeam C, Hanafin N, Holick MF 1990 An evaluation of the relative contributions of exposure to sunlight and of diet to the circulating concentrations of 25-hydroxyvitamin D in an elderly nursing home population in Boston. 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8 VITAMIN D DEFICIENCY AND BONE IN ADULTS 21. Thorsen K, Kristoffersson A, Hultdin J, Lorentzon R 1997 Effects of moderate endurance exercise on calcium, parathyroid hormone, and markers of bone metabolism in young women. Calcif Tissue Int 60: Landin-Wilhelmsen K, Wilhelmsen L, Lappas G, Rosen T, Lindstedt G, Lundberg PA, Wilske J, Bengtsson BA 1995 Serum intact parathyroid hormone in a random population sample of men and women: Relationship to anthropometry, lifestyle factors, blood pressure, and vitamin D. Calcif Tissue Int 56: Herfarth K, Schmidt-Gayk H, Graf S, Maier A 1992 Circadian rhythm and pulsatility of parathyroid hormone secretion in man. Clin Endocrinol (Oxf) 37: Formica CA, Nieves JW, Cosman F, Garrett P, Linsay R 1998 Comparative assessment of bone mineral measurements using dual X-ray absorptiometry and peripheral quantitative computed tomography. Osteoporos Int 8: Ryan PJ, Blake GM, Herd R, Parker J, Fogelman I 1994 Postmenopausal vertebral osteoporosis: Can dual energy X-ray absorptiometry forearm bone density substitute for axial measurements? Br J Rheumatol 33: Selby PL, Davies M, Adams JE, Mawer EB 1999 Bone loss in celiac disease is related to secondary hyperparathyroidism. J Bone Miner Res 14: Krall EA, Dawson-Hughes B 1999 Smoking increases bone loss and decreases intestinal calcium absorption. J Bone Miner Res 14: de Valk-de Roo GW, Netelenbos JC, Peters-Muller IR, Voetberg GA, van de Weijer PH, Bouman AA, Popp-Snijders C, Kenemans P 1997 Continuously combined hormone replacement therapy and bone turnover: The influence of dydrogesterone dose, smoking and initial degree of bone turnover. Maturitas 28: Välimäki M, Kärkkäinen M, Lamberg-Allardt C, Laitinen K, Alhava E, Heikkinen J, Impivaara O, Makela P, Palmgren J, Seppanen R 1994 Exercise, smoking, and calcium intake during adolescence and early adulthood as determinants of peak bone mass. BMJ 309: Heinonen A, Kannus P, Sievänen H, Oja P, Pasanen M, Rinne M, Uusi-Rasi K, Vuori I 1996 Randomised controlled trial of effect of high-impact exercise on selected risk factors for osteoporotic fractures. Lancet 348: Address reprint requests to: Christel Lamberg-Allardt, Ph.D. Department of Applied Chemistry and Microbiology Division of Nutrition, Calcium Research Unit Latokartanonkaari 11, P.O. Box 27 University of Helsinki FIN Helsinki, Finland Received in original form September 8, 2000; in revised form March 7, 2001; accepted May 9, 2001.