Dietary silicon intake is positively associated with bone mineral density in men and premenopausal women of the framingham offspring cohort

JOURNAL OF BONE AND MINERAL RESEARCH
Volume 19, Number 2, 2004
Published online on December 16, 2003; doi: 10.1359/JBMR.0301225
2004 American Society for Bone and Mineral Research
Dietary Silicon Intake Is Positively Associated With Bone Mineral Density in Men and Premenopausal Women of the Framingham Offspring Cohort Ravin Jugdaohsingh,1,6 Katherine L Tucker,2,6 Ning Qiao,2 L Adrienne Cupples,3 Douglas P Kiel,4 and Jonathan J Powell1,5 ABSTRACT: The role of dietary silicon in bone health in humans is not known. In a cross-sectional,
population-based study (2847 participants), associations between dietary silicon intake and BMD were
investigated. Dietary silicon correlated positively and significantly with BMD at all hip sites in men and
premenopausal women, but not in postmenopausal women, suggesting that increased silicon intake is associ-
ated with increased cortical BMD in these populations.
Introduction: Osteoporosis is a burgeoning health and economic issue. Agents that promote bone formation are
widely sought. Animal and cellular data suggest that the orthosilicate anion (i.e., dietary silicon) is involved in bone
formation. The intake of silicon (Si, ϳ30 mg/day) is among the highest for trace elements in humans, but its
contribution to bone health is not known.
Materials and Methods: In a cross-sectional, population-based study, we examined the association between silicon
intake and bone mineral density (BMD) in 1251 men and 1596 pre- and postmenopausal women in the Framingham
Offspring cohort (age, 30 – 87 years) at four hip sites and lumbar spine, adjusting for all potential confounding factors
known to influence BMD and nutrient intake.
Results: Silicon intake correlated positively with adjusted BMD at four hip sites in men and premenopausal women,
but not in postmenopausal women. No significant association was observed at the lumbar spine in any group.
Categorical analysis by Si intake, or energy-adjusted Si intake, supported these findings, and showed large
differences in BMD (up to 10%) between the highest (Ͼ40 mg Si/day) and lowest (Ͻ14 mg Si/day) quintiles of
silicon intake. A significant association at the lumbar spine in men was also observed. Further analyses indicated that
some of the effects seen for moderate consumption of alcoholic beverages on BMD might be attributed to Si intake.
Conclusions: These findings suggest that higher dietary silicon intake in men and younger women may have salutary
effects on skeletal health, especially cortical bone health, that has not been previously recognized. Confirmation of
these results is being sought in a longitudinal study and by assessment of the influence of silicon intake on bone
markers in this cohort.
J Bone Miner Res 2004;19:297–307. Published online on December 16, 2003; doi: 10.1359/JBMR.0301225
Key words:
silicon, bone mineral density, bone formation, dietary intake, beer
INTRODUCTION
SILICON, AS THE soluble silicate anion [orthosilicic acid; *Preliminary results from this study were presented at the 23rd tant in bone formation in both animal and cellular Annual Meeting of the American Society for Bone and Mineral models.(1–4) In 1972, Carlisle(2) and, Schwarz and Milne(3) Research in Phoenix, Arizona, October 12–16, 2001, and an abstractwas published (Tucker KL, Kiel DP, Powell JJ, Qiao N, Hannan MT, showed in independent animal studies that silicon defi- Jugdaohsingh R 2001 Dietary silicon and bone mineral density: The ciency had profound negative influences on skeletal devel- Framingham Study. J Bone Miner Res 16:S1;S510). The final data of
opment. The development of both extracellular matrix (col- this manuscript were presented at the International Bone Mineral lagen) and bone mineral (hydroxy-apatite) was suboptimal Society meeting in Osaka, Japan, June 3–7, 2003, and an abstract wasalso published (Jugdaohsingh R, Tucker KL, Kiel DP, Qiao N, Powell, with silicon depletion.(2,3) Although silicate transporters JJ 2003 Silicon intake is a major dietary determinant of bone mineral have been identified in lower organisms with high silicon density in men and pre-menopausal women of the Framingham Off- requirements,(5) as have silicate responsive and controlling spring cohort. Bone 32:S192).
proteins,(6,7) considerably less is known about this ion in The authors have no conflict of interest.
1Gastrointestinal Laboratory, The Rayne Institute, St Thomas’ Hospital, London, United Kingdom; 2Jean Mayer U.S. Department of Agriculture Human Nutrition Research Centre on Aging, Tufts University, Boston, Massachusetts, USA; 3Department of Biostatistics,Boston University School of Public Health, Boston, Massachusetts, USA; 4Harvard Medical School Division on Aging, HRCA Researchand Training Institute, Boston, Massachusetts, USA; 5MRC Human Nutrition Research, Elsie Widdowson Laboratory, Cambridge, UnitedKingdom; 6These authors contributed equally.
JUGDAOHSINGH ET AL.
mammalian species, especially in humans. In particular, the MATERIALS AND METHODS
complexities of aqueous silicate chemistry and silicon anal- ysis have inhibited detailed mechanistic studies with phys-iological levels of silicon. Nonetheless, low levels of ortho- Subjects in this study were participants in the Framing- silicic acid, at typical plasma concentrations after ingestion ham Osteoporosis Study, drawn from the Framingham Off- of silicon-containing foods, stimulate human osteoblasts spring cohort. The original population-based Framingham and osteoblast-like cells to secrete type I collagen and other Heart Study was initiated in 1948 to examine the risk factors markers involved in bone cell maturation and bone forma- for heart disease.(18) The Original cohort constituted a two- tion.(4) Soluble silicate may stabilize aqueous hydroxy- thirds sampling of the households in Framingham, MA.(18) radical species,(8) and some have suggested silicate involve- The Offspring cohort was established in 1971 and consists of the children (and their spouses) of the Original cohort pathway(9) during type I collagen formation. Others have members. Members return every 4 years for a physicalexamination and to complete a series of questionnaires and suggested a structural role in the cross-linking and stabili- tests. In the fifth (1991–1995) and sixth (1995–1999) study zation of collagen and glycoaminoglycans.(10) Further stud- visits (or examination cycles), there were 3799 participants ies are required at the molecular and mechanistic level, but (1605 men and 1813 women, 30 – 87 years of age), of which the finding that orthosilicic acid stimulates human osteo- 1251 men and 1596 women had completed two semiquan- blasts is important and consistent with the few small studies titative food frequency questionnaires (FFQ) and had BMD in human subjects(11,12) and the numerous studies in measurements performed between 1996 and 2001. All par- ticipants with dietary intake data and BMD measurement The average daily dietary intake of silicon in the West- were included in this study; otherwise, there were no ex- ern world is about 20 –50 mg/day, although it is lower in clusion criteria (i.e., for bone diseases, other diseases, women (24 Ϯ 12 mg/day at the age of 26 –39 years) than women with premature menopause or bilateral ovariectomy, men (37 Ϯ 23 mg/day at the age of 26 –39 years), and or subjects on treatments for bone diseases or other dis- decreases with age (ϳ0.1 mg lower for each year after eases). The study was approved by the Institutional Review 26 –39 years of age).(13,14) Recently, we demonstrated Board for Human Research at Boston University (Boston, that common silicon-rich foods effectively deliver bio- MA, USA) and the Hebrew Rehabilitation Center for Aged available silicon after their ingestion by human volun- (Boston, MA, USA). Written informed consent was ob- teers.(13) Phytolithic (plant-based) silicates seem to un- dergo hydrolysis, forming orthosilicic acid, in the gastrointestinal tract, because soluble orthosilicic acid,but not polysilicate, is well absorbed in human sub- Dietary silicon intake and major food contributors to Si jects.(15) Major sources of dietary Si in the Western world intake in this population have been previously described by are cereals/grains and their products (e.g., breakfast ce- the authors.(13) Usual dietary intake, in the Offspring cohort, reals, bread, beer), some fruits and vegetables (e.g., ba- was assessed using the Willett semiquantitative 126-item nanas, raisins, beans, lentils), and unfiltered drinking FFQ.(19) This questionnaire has been validated for many water.(13) It seems likely that food preparation in the nutrients and in several populations.(19) Before the fifth Western world has reduced our silicon exposure in recent (1991–1995) and sixth (1995–1999) study visits, question- times,(16) especially due to the treatment of drinking naires were mailed to the subjects, who were asked to water, the processing of cereals, and possibly the hydro- complete them based on their pattern of intake over the ponic growth of vegetables.(17) As for all nutrients, how- previous year and to bring them to their appointments(visits). A completed FFQ was available from both study ever, individual dietary habits mostly dictate our expo- visits. The average intake from the two questionnaires was used. Completed questionnaires were excluded, as previ- We showed recently that the silicon content of foods is a ously reported,(13,20) if calculated energy intakes were be- proxy for silicon absorption in human subjects,(13) so the low 2.51 MJ/day, above 16.74 MJ/day for women and 17.57 aims of this study were, first, to determine the relationship MJ/day for men, or if more than 12 food items were left between dietary Si intake and bone mineral density (BMD) blank. Processing of the forms to obtain total daily energy (adjusting for all potential confounders known to affect intakes and food intake was carried out at Harvard Univer- BMD and nutrient intake, with and without the inclusion of alcohol intake) and to assess whether the relationship holdsacross different bone sites, gender, and menopausal status.
We also examined the association between sex-specific Silicon values per 100 g edible portion of each of the 278 quintiles of Si intake and BMD to investigate the possibility food items in the FFQ were obtained from a previous review of nonlinear relationships. Second, we determined whether by Pennington.(14) The Si contents of composite foods were or not the positive relation between the moderate ingestion calculated from the individual components of the food.
of alcoholic beverages and BMD, observed in this cohort, However, where values for reported Si levels of foods could be explained by Si intake. We hypothesized that there varied between laboratories by 3-fold or more, additional would be a positive association between silicon intake and analyses were made independently by the authors (King’s College London), and with the exception of liquor (0.13 Ϯ SILICON AND BMD
0.04 mg/100 g; range, 0.06 – 0.21 mg/100 g), beer (2.06 Ϯ of calcium (mg) and/or vitamin D supplements (IU) was 0.70 mg/100 g; range, 0.96 –3.94 mg/100 g), and orange obtained from the supplement section of the FFQ. Estrogen juice (0.01 Ϯ 0.01 mg/100 g; range, 0.0004 – 0.25 mg/100 use in women was defined as those currently receiving g), our data correlated highly (r ϭ 0.82; n ϭ 28) with those estrogen therapy at the time of BMD measurements, with of Varo (extensively cited by Pennington(14)). Therefore, as continuous use for Ն1 year.(24) Information on the use of reported previously,(13) we chiefly used the values of Varo other osteoporosis medication (e.g., bisphosphonates, selec- with our values for orange juice, beer, and liquor, in the tive estrogen receptor modulators, calcitonin) was obtained database. These values (mg Si/100 g food) were entered into during the course of the bone density measurements (1996 – a database program in the Dietary Assessment and Epide- 2001). Other drugs that may affect BMD (corticosteroids, miology Research Program at Tufts University (Boston, thyroxine) were not included in the models. Total energy MA, USA) and corrected for the weight of each food item intake in calories (converted to Joules), total protein intake reported for each individual participant. Because the Si (g), dietary calcium intake (mg), dietary vitamin D intake content of foods was recorded on a dry weight basis, levels (IU), magnesium (mg) and potassium intake (mg), and of Si in brown rice, white rice, and pasta were corrected by intake of alcohol (see above) were averaged from the two 0.30, 0.39, and 0.30, respectively, based on United States FFQs from the 1991–1995 and 1995–1999 study visits.
Department of Agriculture (USDA) published (raw to Smoking status (current, past, or nonsmoker) was obtained cooked) conversions.(21) The values (mg Si) for each food at 1995–1999 study visit. Finally, to control for potential item were summed to obtain total Si intake per person per seasonal effects on BMD measures, a categorical variable day in each of two study visits (1991–1995 and 1995–1999).
for time of BMD measurement was created.(20) July, Au- The average silicon intake (mg/day) from the two visits was gust, and September were coded as summer; October, No- vember, and December as fall; January, February, andMarch as winter; and April, May, and June as spring.
Intake (servings per day, per week, or per month) of beer, wine, and liquor were averaged from the two FFQs from the All analyses were conducted separately for men and pre- 1991–1995 and 1995–1999 study visits. One serving of beer and postmenopausal women and were performed with PC represented one 356-ml glass, bottle, or can, while one SAS for Windows (version 8.1; SAS Institute Inc., Cary, serving of wine (red or white) represented one 4-oz glass NC, USA). We initially investigated the association be- (118 ml), and one serving of liquor represented one drink or tween silicon intake and BMD (at the four hip sites and lumbar spine) using Si as a continuous variable in thegeneral linear models. Because the distribution of silicon intake was found to be skewed, the data were transformedby natural logarithm (ln). Measures of BMD at the hip sites BMD was measured between 1996 and 2001, during the and lumbar spine were regressed on the ln value of the course of the sixth and seventh examination cycles, using average silicon intake from the two exams. Adjustment was DXA (Lunar DPX-L; Lunar Radiation Corp, Madison, WI, made for potential confounders known to influence BMD USA). BMD was measured at the left hip (total hip, tro- and nutrient intake, namely age, height, BMI, physical chanter, Ward’s area, and femoral neck) and at the lumbar activity score, smoking status, calcium intake (dietary and spine (L –L ). The precision (CV) was 1.7% at the femoral supplement use), vitamin D intake (dietary and supplement neck, 2.5% at the trochanter, and 0.9% at the spine.
use), estrogen use (in women), use of other osteoporosismedication, season of BMD measurement, energy intake, protein intake, magnesium and potassium intakes, and with Potentially confounding variables, known to influence and without the inclusion of total alcohol intake. Because BMD and nutrient intake that are routinely used in this type beer is a major source of Si and alcohol intake has been of study, measured at the time of bone density measure- previously associated with BMD in the original Framing- ments (in the sixth examination cycle [1995–1999]), were ham cohort,(25) analyses were repeated with the adjustment obtained for each participant, along with overall medical for alcohol based on non-beer alcohol. Non-beer alcohol history. Potential confounding factor(s) that may influence was defined as all alcoholic beverages other than those Si intake are still not clear, although the usual adjustments classed as beer (i.e., wine and liquor).
were made for energy and potentially colinear nutrients.
A number of dietary components do not adhere to linear Age (years), height in inches (converted to meters), and relationships, such as alcohol (hyperbolic)(25) and many weight in pounds (converted to kilograms) were measured, nutrients (threshold),(26) so in addition to treating silicon and body mass index (BMI) was calculated (kg/m2). BMI intake as a continuous variable, and to avoid assumption of (relative weight considering height) and height were in- linearity between intake and BMD measures, sex-specific cluded in the statistical models, instead of weight and quintiles of silicon intake were created, and adjusted BMD height, which generally are too highly correlated (colinear) means (including adjustment for alcohol based on non-beer for appropriate inclusion in the same model.(22) Results in alcohol) were compared across these categories. To confirm this study differed negligibly using either of these combi- that these associations were caused by Si and not a factor nations. Physical activity was examined using the Physical colinear with Si or because of inadequate adjustment of a Activity Scale for the Elderly (PASE) questionnaire.(23) Use confounder, we investigated by Pearson correlations poten- JUGDAOHSINGH ET AL.
TABLE 1. CHARACTERISTICS OF THE STUDY POPULATION WITH BMD MEASURES* * Means Ϯ SD.
† Bisphosphonates (FOSAMAX and DIDRONEL), selective estrogen receptor modulator (EVISTA), and calcitonin (CALC-SPR).
tial colinearity between silicon intake and a number of physical and dietary variables, namely age, height, weight, BMI, physical activity score, estrogen use in women, smok-ing status, total energy intake, protein intake, total alcohol Characteristics of men and pre- and postmenopausal intake, non-beer alcohol intake, and beer intake. The anal- women in the study sample are shown in Table 1. There yses between sex-specific quintiles of silicon intake and were 306 premenopausal women, 1295 men, and 1325 adjusted BMD were repeated for energy-adjusted silicon postmenopausal women in the study sample. Premeno- intake, computed using the residual method, as described by pausal women had the lowest mean age and BMI of the three groups and the highest physical activity score. Post- Finally, associations between BMD and beer intake, and menopausal women had the lowest mean weight, height, BMD and non-beer alcohol intake, were assessed in the and physical activity score. A higher percentage of men general linear models with all the adjustments above (in- (66%) were beer drinkers (i.e., drank some beer) compared cluding intake of other alcoholic beverages), with and with- with pre- (37%) and postmenopausal (24%) women, and this was reflected in their mean silicon intakes (see below).
Results are expressed as mean Ϯ SE, unless otherwise For all groups, 39 –53% drank some liquor, and 59 –73% stated. Multiple linear regression (equivalently, analysis ofcovariance) was used to calculate adjusted least-squares drank some wine. Energy intake was highest in men and means for BMD at each bone site according to sex-specific lowest in postmenopausal women. Protein intake was sim- quintiles of silicon intake. The p value for a test for trend in ilar in the three groups (Table 1). Silicon intake and major increasing BMD with increasing quintile of silicon intake sources of intake in this cohort are shown in Tables 1 and 2, was also obtained from multivariable linear regression mod- respectively, and are similar to those reported in the same els. Adjusted least-squares means were also compared be- cohort at just one examination (1991–1995).(13) Calcium tween quintiles using post hoc t-tests. All analyses were and vitamin D supplement use was highest in postmeno- conducted separately for pre- and postmenopausal women pausal women (35% and 4%, respectively), and this group and men using the GLM procedure in SAS.
had the highest estrogen use (34%) as well as other osteo- SILICON AND BMD
TABLE 2. TOP 10 CONTRIBUTING FOODS TO TOTAL SILICON INTAKES IN THE STUDY POPULATION* porosis medications (4%). BMD, at all sites, was lowest in pausal women than for men (Fig. 1). However, because of the large differences in numbers (n ϭ 306 and 1295 forpremenopausal women and men, respectively), this was not Linear association between Si intake and BMD: effect always reflected in the significance levels.
Because nutritional effects are most marked and com- Silicon intake was positively associated with BMD at all monly reported between the lowest and highest percentiles hip sites for men and for premenopausal women, but not for of nutrient intake,(26) we investigated differences in BMD postmenopausal women (Table 3), after adjusting for all between those in the highest versus the lowest quintiles of potential confounders except the intake of alcohol. The Si intake. The results indicated marked significant differ- mean Ϯ SD difference in BMD at the four hip sites per ln ences in BMD at the hip sites for both premenopausal unit difference in Si intake was 0.085 Ϯ 0.010 g/cm2 (or women (average, 9.9 Ϯ 2.0%; p Յ 0.02, except Ward’s 9.6 Ϯ 2.0%) for premenopausal women (p Յ 0.04), 0.040 Ϯ area, p ϭ 0.07) and men (5.1 Ϯ 0.8%; p Յ 0.03), with little 0.003 g/cm2 (or 4.3 Ϯ 0.4%) for men (p Յ 0.05), and overlap between the groups (i.e., the highest and lowest Ϫ0.010 Ϯ 0.007 g/cm2 (or Ϫ1.3 Ϯ 0.9%) for postmeno- quintiles; Fig. 1), but not for postmenopausal women pausal women (p Ն 0.23). There was no significant associ- (Ϫ0.15 Ϯ 0.57%; p Ն 0.7). Similarly, differences in BMD ation between Si intake and BMD of the lumbar spine in any between the highest and lowest quintiles were suggestive at group (Table 3). The ␤ coefficients were largely unchanged the lumbar spine for premenopausal women (5.1%; p ϭ after additional adjustments for the intake of beer and/or 0.16) and men (4.5%; p ϭ 0.039), but not for postmeno- non-beer alcohol, although significance was sometimes pausal women (Ϫ0.41%; p ϭ 0.86).
weaker with these additional adjustments (Table 3).
There was no correlation between silicon intake and any potentially confounding variable except total energy intake,protein intake, total alcohol, and beer, which were positively To investigate the possibility of nonlinear relationships correlated as shown in Table 4; only energy intake had a and threshold effects, we also examined BMD across sex- correlation in the range of colinearity with silicon intake specific quintiles of Si intake. The groupings (quintiles) (r ϭ 0.67 and 0.62 for women and men, respectively). As revealed silicon intakes (per day) of 7.1–16.7, 16.7–20.7, may be expected, energy and nutrient intakes commonly 20.7–24.6, 24.6 –30.2, and 30.2– 63.2 mg for premenopausal show some degree of colinearity, and energy-adjusted nu- women, 7.6 –18.8, 18.8 –23.9, 23.9 –28.5, 28.5–34.4, and34.4 –118.0 mg for men, and 5.9 –16.4, 16.4 –20.4, 20.4 – trient intakes may be used to correct for this.(20,26,27) Here 24.1, 24.1–29.9, and 29.9 – 83.5 mg for postmenopausal we used the residual method to remove the variation in Si women (Fig. 1). The majority of silicon intakes were within intake caused by greater energy intake. After adjustment, a relatively narrow range (23.6 Ϯ 8.9 mg/day for women energy intakes did not significantly differ across sex- and 27.5 Ϯ 10.7 mg/day for men), and along with the specific quintiles of Si intake, but adjusted BMD and corresponding BMDs, were especially similar in the middle energy-adjusted silicon intake remained positively associ- three quintiles (Fig. 1). Again, however, even when BMD ated for both premenopausal women and men (Fig. 2).
was adjusted for all potential confounders including the Differences between the lowest and highest quintiles of intake of alcohol, significant positive associations were seen energy-adjusted silicon intake were, however, reduced by between sex-specific quintiles of silicon intake and BMD for premenopausal women and men, but not for postmeno- unadjusted silicon intakes, whereas the middle three quin- pausal women (Fig. 1). We observed a more marked asso- tiles became more similar in magnitude to the first quintiles ciation between Si intake and adjusted BMD for premeno- for both adjusted BMD and Si intakes (Fig. 1 versus Fig. 2).
JUGDAOHSINGH ET AL.
TABLE 3. LINEAR REGRESSION ANALYSIS OF SILICON INTAKE (LOG-TRANSFORMED) AND ADJUSTED BMD* AT THE FOUR HIP SITES AND THE LUMBAR SPINE WITH AND WITHOUT ADJUSTMENT FOR TOTAL ALCOHOL AND NON-BEER ALCOHOL INTAKE * Adjusted for age, height, BMI, physical activity score, smoking status, calcium intake (diet and from supplement use), vitamin D intake (diet and supplement use), estrogen use (in women), use of other osteoporosis medications, season of BMD measurement, energy intake, protein intake, magnesiumand potassium intakes, and alcohol intake as indicated.
† N ϭ 299; ‡N ϭ 300; §N ϭ 1220; ¶N ϭ 1221; **N ϭ 1260; ††N ϭ 1270.
0.06 ϫ 10Ϫ4 g/cm2 per serving). Using this model, theassociation between intake of alcoholic beverages and BMD Similar regression coefficients between BMD and silicon was not significant in premenopausal women; however, intake were seen in drinkers and non-drinkers (whether correcting for silicon intake attenuated the magnitude and/or beer, non-beer alcohol, or total alcohol; data not shown), direction of the ␤ coefficients for BMD and beer (by confirming that the above model adequately adjusted for 11.78 Ϯ 1.58 ϫ 10Ϫ4 g/cm2 per serving; mean Ϯ SD of the alcohol intakes. However, we also considered the reversescenario, namely the possibility that silicon intake may four hip sites) but had little effect on BMD and non-beer affect the association between BMD and alcohol in- alcohol (increased by 1.15 Ϯ 0.15 ϫ 10Ϫ4 g/cm2 per serv- take.(25,28) We investigated, using the simple linear model, ing), again suggesting that the effect is either from Si or at whether adjustment for silicon intake would modulate the ␤ least a component strongly colinear with silicon.
coefficients when BMD was regressed on alcohol intake inmen and premenopausal women. This analysis was not DISCUSSION
aimed at studying the effect of alcohol intake on BMD,which is nonlinear, but to see if adjustment using a global To our knowledge, this is the first population-based model for silicon would attenuate the ␤ coefficient for BMD (cross-sectional) study to examine the specific association and beer (a high contributor to dietary silicon) but not for between dietary silicon intake and BMD in men and BMD and non-beer alcohol (a low contributor to dietary women. These findings indicate significant positive associ- silicon). In men, adjustment for silicon intake reduced the ations between silicon intake and BMD at the hip sites for positive association by 2.34 Ϯ 0.45 ϫ 10Ϫ4 g/cm2 per men and premenopausal women, but not for postmeno- serving (mean Ϯ SD of the four hip sites) and negated the pausal women. No significant correlation was found at the significance between beer intake and BMD, but had little lumbar spine except in men, and only then in one of the effect on non-beer alcohol and BMD (increased by 0.32 Ϯ SILICON AND BMD
Associations between silicon intake and mean Ϯ SE adjusted BMD at the four hip sites and lumbar spine for premenopausal women, men, and postmenopausal women. BMD was adjusted for all known potential confounding factors known to influence BMD and nutrient intake,and alcohol, based on non-beer alcohol. Silicon intake is shown as quintiles, and the adjusted BMD is plotted against the mean silicon intake foreach quintile. Test for linearity/trend across quintiles of silicon intake was significant at the total hip (p ϭ 0.04) and trochanter (p ϭ 0.004) forpremenopausal women and at the all hip sites except Ward’s area for men (p ϭ 0.04, 0.01, and 0.03 for total hip, femoral neck, and trochanter,respectively). Difference in BMD between the lowest and highest quintile of silicon intake was also significant at all bone sites except for Ward’sarea and lumbar spine in premenopausal women (p ϭ 0.02, 0.02, and 0.003 for total hip, femoral neck, and trochanter, respectively) and at allbone sites for men (p ϭ 0.02, 0.007, 0.02, 0.03, and 0.04 for total hip, femoral neck, trochanter, Ward’s area, and lumbar spine, respectively).
Axes (x and y) are the same magnitude for ease of comparison between BMD sites and subject groups.
TABLE 4. CORRELATION COEFFICIENTS* BETWEEN SILICON INTAKE AND A NUMBER OF PHYSICAL AND DIETARY VARIABLES The average difference in BMD between individuals with premenopausal women. Other nutrients associated with in- the lowest and highest quintile of silicon intake was 0.047– creases in BMD of the femoral neck (e.g., calcium,(26,29,30) 0.082 g/cm2 (or 5.0 – 8.9%) in the femoral neck for men and magnesium,(20,26) potassium,(20,26) and vitamins C(26) and JUGDAOHSINGH ET AL.
Associations between energy-adjusted silicon intake and mean Ϯ SE adjusted BMD at the four hip sites and lumbar spine for premenopausal women, men, and postmenopausal women. BMD was adjusted for all known potential confounding factors known to influenceBMD and nutrient intake, and non-beer alcohol. Energy-adjusted silicon intake is shown as quintiles, and the adjusted BMD is plotted against themean energy-adjusted silicon intake for each quintile. Test for linearity/trend across quintiles of energy-adjusted silicon intake was significant atall bone sites except Ward’s area and lumbar spine for premenopausal women (p ϭ 0.04, 0.03, and 0.004 for total hip, femoral neck, andtrochanter, respectively) and at all bone sites except Ward’s area for men (p ϭ 0.02, 0.006, 0.004, and 0.04 for total hip, femoral neck, trochanter,and lumbar spine, respectively). Difference in BMD between the lowest and highest quintile of silicon intake was also significant at all bone sitesexcept for Ward’s area and lumbar spine in premenopausal women (p ϭ 0.03, 0.03, and 0.003 for total hip, femoral neck, and trochanter,respectively) and at all bone sites for men (p ϭ 0.03, 0.01, 0.01, 0.04, and 0.03 for total hip, femoral neck, trochanter, Ward’s area, and lumbarspine, respectively). Axes (x and y) are the same magnitude for ease of comparison between BMD sites and subject groups.
K(31)) generally show maximum differences between the The striking difference in silicon effects between post- high and low nutrient intake groups of 0.025– 0.04 g/cm2, menopausal women and either men or premenopausal one-half that observed for silicon. Even controlling for total women may have a plausible, biological explanation.
energy intake (Fig. 2), which correlated with Si intake, the From a biological perspective, these and previous effects of Si were at least comparable with those of other results(1– 4) point toward the role of orthosilicic acid in bone formation but not in bone resorption. In postmeno- Because this is the first study of the associations be- pausal women, BMD is driven by resorptive process- tween silicon intake and BMD, comparison of our results es,(32,33) and silicon would be expected to have no role in with others cannot readily be made. However, recent ameliorating this effect. However, it is interesting that studies in cultured human osteoblasts(4) and in animal dietary Si had no effect on the BMD of postmenopausal models(1–3) support the finding that Si promotes bone women, suggesting that hormonal factors may over- formation. Longitudinal analysis and correlation between whelm any nutrient effects on bone. It is possible that the dietary silicon intake and bone markers, which are to bone-promoting effects of dietary silicon are attenuated follow in this cohort, will address the consistency of postmenopausally. For example, in the postmenopausal state, circulating estradiol levels are markedly reduced, SILICON AND BMD
and expression of estrogen receptors are downregulated cross-sectional; therefore, whereas a relation between Si in bone.(34,35) In contrast, in older men, there is little intake and BMD is indicated, caution must be exercised change in the expression of estrogen receptors in bone when drawing conclusions about the influence of Si on while aromatization of testosterone contributes to tissue bone health.(26) Second, BMD was adjusted for all po- tential confounders including energy intake, alcohol in- Estrogen receptors are potent transcription factors for a take, and BMI, but we cannot rule out the possibility of number of genes, and recently, certain transport and tissue- some imperfect adjustment(s). Mean BMI was above 25 specific activities of zinc have been shown to be regulated kg/m2 in all three groups, so a proportion of the subjects by estrogen levels and expression of estrogen receptors.(37) were overweight (BMI ϳ 25–29.9 kg/m2) or obese Whether the same may be true for Si in bone remains to be (BMI Ն 30 kg/m2), and the influence of body weight on determined, but it is of interest to note that the absorption BMD is well established.(42– 44) However, the use of and tissue distribution of silicon is reportedly affected by energy-adjusted silicon intakes should additionally cor- sex hormone levels.(38) Finally, it should be noted that pre- rect for this, while any confounding effects would have to and postmenopausal dietary habits may differ, making past explain the markedly different results between the three nutrient exposure difficult to gauge from current intakes groups. Finally, some unmeasured factor may be respon- rather than suggesting that earlier, premenopausal effects of sible for the observed relationship between Si and BMD, dietary silicon on BMD are lost over time.
although this would have to be highly colinear with Si For many nutrients, intake and BMD do not correlate intake. Overall, however, the positive relationship be- in a simple linear fashion.(26) As seen here for silicon, tween dietary silicon and BMD in men and premeno- differences in BMD are often most clearly observed when pausal women, the reproducibility of these effects across comparing groups with high and low intakes of a specific the different hip sites, and the consistency of these find- nutrient or food group.(20,26) It is possible that silicon ings with other biological models suggest that dietary deficiency is more apparent in individuals in the lowest silicon may be important for bone health in men and quintile of silicon intake, explaining a dramatically lower premenopausal women. Confirmation of these findings is BMD compared with other quintiles. In contrast, those in the highest quintile of silicon intake could experience a Finally, it is noteworthy that, in the Western world, one promoting, rather than maintenance, effect of silicon on major potential source of bioavailable and bioactive sil- BMD. Indeed, in ovariectomized rats, a model mimicking icon is from beer ingestion, at least for men (Table the postmenopausal state, very high levels of dietary 2).(13,14) The positive effect of moderate alcohol con- silicon completely abrogate bone mineral loss and in- sumption on BMD has been well reported and seems to crease bone mineral content (BMC).(1) Thus, whether be relatively consistent for men and pre- and postmeno- pharmacologic levels of silicon can overcome the lack of pausal women.(28) This may be primarily because of a responsiveness to dietary silicon in postmenopausal direct or indirect effect of alcohol on bone resorp- women needs to be established. Two previous pilot stud- tion.(45,46) However, based on our findings, the additional ies using organosilicon compounds suggests that this is “silicon effect” adds a further dimension with moderate beer consumption, which is likely to act on bone forma- It is not known why the association between Si intake and tion. We therefore also provide the first evidence to lumbar spine BMD was much weaker compared with the support the view that not all the effects of alcoholic hip sites, because cancellous (or trabecular) bone is often beverages on BMD, and perhaps other outcome mea- more affected by metabolic factors than cortical bone be- sures, are attributable to ethanol. The other sources of cause of its higher rate of turnover. However, if the affect of dietary Si such as whole grains, rice, certain vegetables silicon is anabolic (i.e., promoting bone formation rather and fruits, and natural waters would suggest that micro- than inhibiting resorption), one clue may be provided by nutrients in whole foods and untreated water may con- recent work with parathyroid hormone, where, at least in tribute importantly to bone health in men and premeno- mice, its anabolic action is significantly greater on cortical bone than it is on cancellous bone.(39) In support of this, aprevious study in osteoporotic women reported a much ACKNOWLEDGMENTS
larger increase in BMD at the hip compared with the spineafter supplementation with a pharmacologic dose of Si, The authors thank Janice Maras of Tufts University whereas in contrast, the other factors tested (etidronate, (Boston, MA, USA) for database development and anal- fluoride, and magnesium) affected the spine much more ysis of silicon intake in the Framingham study, Dr Eliz- greatly than the hip, suggesting that Si may indeed prefer- abeth Samelson (HRCA Research and Training Institute, entially affect cortical bone.(12) In addition, the lumbar spine Boston, MA, USA) and Dr Henk Hendriks (TNO Nutri- is also the site of artifactual calcifications such as degener- tion and Food Research, The Netherlands) for useful ative spine changes and vascular calcification, and these discussions, and Prof Sir Richard Thompson (St Thomas’ could mask and thus weaken the association between Si Hospital, UK) for continuous support. Funding for this work was provided by the U.S. Department of Agricul- This study sought a single a priori hypothesis in a ture (contract 53-3K06-5-10), National Institutes of large, well-described population. However, the limita- Health (RO1 AR/AG 41398), and the Framingham Heart tions of this study are recognized. First, the data are Study (supported by National Institutes of Health/NHLBI JUGDAOHSINGH ET AL.
contract NO1-HC-38038). The sponsors had no involve- 22. Michels K, Greenland S, Rosner BA 1998 Does body mass index ment in this study (i.e., in the design, collection, analysis, adequately capture the relation of body composition and body size
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Received in original form April 24, 2003; in revised form August 11, 2003; accepted September 10, 2003.

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