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1 From the Bone Metabolism Unit and the Cardiac Center, Creighton University, School of Medicine, Omaha.
See corresponding editorial on page 1073.
ABSTRACT
Background: Published reports on the effect of alcohol consumption on bone mineral density (BMD) are inconsistent.
Objective: The objective of this study was to examine the relation between alcohol intake and BMD, calcitropic hormones, calcium absorption, and other biochemical indexes of bone and mineral metabolism in elderly women.
Design: The results presented are derived from baseline observations of 489 elderly women (aged 65–77 y) recruited for an osteoporosis study. The nondrinking group comprised 297 women and the drinking group comprised 148 women. Furthermore, the effect of different alcohol intakes (28.6, >28.6 to 57.2, >57.2 to 142.9, and >142.9 g/wk) was studied.
Results: Women who consumed alcohol had significantly higher spine (10%), total body (4.5%), and midradius (6%) BMD than did nondrinkers. An alcohol intake >28.6 g/wk was associated with higher BMD; maximum effect was seen with an intake of >28.6 to 57.2 g/wk (16%, 12%, and 14% increase in spine, total body, and midradius BMD, respectively). There was a marked reduction in bone remodeling markers, serum osteocalcin, and the ratio of urinary cross-linked N-telopeptides of type 1 collagen to creatinine with alcohol consumption, suggesting that increased BMD with alcohol consumption could be due to reduced bone remodeling. Further, serum parathyroid hormone concentrations were significantly lower in alcohol drinkers than in nondrinkers and could be one of the causes of decreased bone resorption.
Conclusions: Moderate alcohol intake was associated with higher BMD in postmenopausal elderly women. The protective effect of alcohol may have been a result of lower bone remodeling due to reduced parathyroid hormone concentrations or factors such as increased estrogen concentrations.
Key Words: Alcohol • bone mineral density • BMD • bone remodeling • serum parathyroid hormone • elderly women
INTRODUCTION
Osteoporosis is a major public health problem in the elderly population of Western countries, affecting mostly women. It is the most important underlying cause of spine and hip fractures in elderly men and women. Of the various multiple risk factors, nutritional and lifestyle factors are recognized as important in the etiology of osteoporosis. Since the initial work of Saville (1, 2), alcohol consumption has been known to be a significant contributing factor to osteoporosis and osteoporotic fractures.
Several studies showed that chronic alcoholism leads to osteopenia and increased incidence of skeletal fractures (3–5). Studies carried out to understand the underlying mechanism suggested that alcohol may have a direct effect on bone cells and an indirect or modulatory effect through mineral regulatory hormones (6, 7). Alcohol has been shown to decrease the bone formation rate by decreasing the osteoblast number, osteiod formation, and osteoblast proliferation (8–10). However, the effect of alcohol consumption on bone resorption has not been established clearly. Some histomorphometric studies showed increased bone resorption in moderate and heavy drinkers (10), whereas others found no effect (11). In addition, calcitropic hormones, including serum parathyroid hormone (PTH) and vitamin D metabolites, were reported to be altered by alcohol consumption (12, 13).
There are conflicting reports in the literature regarding the effect of moderate alcohol consumption on bone. Some researchers did not find a positive association between moderate alcohol intake and bone mineral density (BMD) (14–21). However, recent studies, mostly in postmenopausal women, showed a positive correlation between BMD and moderate alcohol consumption (22–28). Holbrook and Barrett-Connor (26) reported that social drinking is associated with higher BMD in both men and women. Similar observations were made in a study by Felson et al (27), who found that elderly women with an alcohol intake of 210 mL (7 oz)/wk had higher BMD than did nondrinkers at most sites tested. Fescaniks et al (28) also showed a linear increase in spine density over increasing categories of alcohol intake in postmenopausal women.
In the present study, we examined the effect of alcohol intake on BMD at baseline in elderly women recruited for a multicenter osteoporotic longitudinal study (Sites Testing Osteoporosis Prevention/Intervention; STOP/IT). In addition, we explored the possible mechanism of the effect of alcohol consumption by studying the biochemical variables related to bone and mineral metabolism.
SUBJECTS AND METHODS
The cross-sectional data presented here were derived from the baseline information collected at the Omaha site for 489 women aged 65–77 y who entered STOP/IT. All subjects were volunteers who responded to advertisements in local newspapers or to a mass mailing of letters inviting them to participate in a 3-y study. The recruitment and enrollment period was from November 1992 to February 1994. The subjects included 472 white women, 11 black women, 4 Hispanic women, 1 Asian woman, and 1 woman of mixed race. Subjects were excluded if they were taking medications or had diseases known to influence calcium or phosphorus metabolism. Data for 43 women taking thiazide diuretics and 1 woman with suspected Paget disease were excluded from the analysis. All subjects had normal liver and kidney function for entry into the study. They were free living and had a normal score for activities of daily living. The protocol was approved by the Creighton University Institutional Review Board.
Dietary intake, alcohol consumption, and smoking history
Dietary intake data were collected with use of 7-d food diaries. Plastic food models (NASCO, Fort Artinson, WI) were used to help participants better estimate the quantities consumed. Average daily calcium, vitamin D, and caffeine intakes were calculated by using FOOD PROCESSOR II PLUS (version 5.1; Esha Research, Salem, OR).
The information on alcohol consumption and smoking history was obtained by a self-administered questionnaire. The information on frequency of smoking (ie, number of cigarettes/wk) and the quantity of beer, wine, and mixed drinks (or undiluted spirits) consumed per week was obtained. Total alcohol consumption was computed by multiplying the average amounts of actual alcohol content in the beer, wine, and mixed drinks by the amount drunk with use of the following conversion formula (27):
RESULTS
Characteristics of the study population
A comparison of the characteristics of the study population between nondrinkers and between nondrinkers and subjects in the different categories of alcohol intake are shown in Table 1. The drinkers and nondrinkers were not significantly different with respect to age, height, and dietary calcium, vitamin D, protein, and energy intakes. Compared with the nondrinkers, the drinkers weighed significantly less and had significantly higher caffeine intakes. When compared by the amount of alcohol intake, drinkers with an alcohol intake of >57.2 to 142.9 g/wk had significantly lower body weights than did nondrinkers. Although caffeine intake was marginally higher in all categories of drinkers than in nondrinkers, the values were not significantly different. The mean (±SEM) age at menopause was also significantly higher in drinkers (49.2 ± 0.79 y) than in nondrinkers (47.4 ± 0.42 y). When consumers of different categories of alcohol intake were compared with nondrinkers, none of them were significantly different from nondrinkers with regard to the age at menopause. Subjects in all the categories of alcohol intake were also not significantly different from nondrinkers with regard to age, height, or dietary calcium, vitamin D, protein, and energy intakes; 11.5% of nondrinkers and 18.2% of drinkers were current smokers. The percentage of current smokers in the alcohol intake categories of >57.2 to142.9 and >142.9 g/wk was higher: 23% and 30% of women in these categories, respectively, were current smokers. Eighteen percent of both alcohol drinkers and nondrinkers gave a history of estrogen use of >1 y. The distribution of percentage of past estrogen users was not significantly different between various categories of alcohol intake. Forty-seven percent of nondrinkers and 48% of drinkers had a history of fractures. The rate of history of fractures of consumers of various categories of alcohol intake was not significantly different from that of nondrinkers (nondrinkers, 47.3%; 28.6 g/wk, 44.3%; >28.6 to 57.2 g/wk, 51.5%; >57.2 to 142.9 g/wk, 42.3%; and >142.9 g/wk, 55%; Pearson's chi-square, P < 0.87).
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TABLE 1. Characteristics of the study population1
Bone mineral density
The adjusted mean BMDs at lumbar spine (1.047 ± 0.020 compared with 0.951 ± 0.016 g/cm2, P < 0.000, 10% difference), total body (1.029 ± 0.011 compared with 0.986 ± 0.008 g/cm2, P < 0.001, 4.4% difference), and midradius (0.706 ± 0.013 compared with 0.666 ± 0.010 g/cm2, P < 0.014, 6% difference) were significantly higher in drinkers than in nondrinkers. BMD at the femoral neck (0.776 ± 0.011 compared with 0.756 ± 0.008 g/cm2, P < 0.141) also tended to be higher (2.6%) in drinkers than in nondrinkers. Adjusted mean BMDs at lumbar spine, femoral neck, total body, and midradius according to the category of alcohol intake are presented in Figure 1. When compared by the amount of alcohol intake, subjects in all categories of alcohol intake had higher BMDs than did nondrinkers at lumbar spine, total body, and midradius, though not significantly so at all levels. Of the various categories of alcohol intake, women with an intake of >28.6 to 57.2 g/wk had the highest lumbar spine, total body, and midradius BMD compared with nondrinkers; the differences (all significant) were 16%, 12%, and 14%, respectively, between the 2 groups. Even at the femoral neck, this group of women tended to have higher BMD (6%), but this difference was not significant. Consumption of >57.2 to 142.9 and >142.9 g/wk also tended to increase the BMD at all the sites measured. However, only lumbar spine density (15%) and total body density (5.5%) of subjects in the category of >142.9 g/wk were significantly higher than that of nondrinkers.
FIGURE 1. . Adjusted mean (±SEM) lumbar spine, femoral neck, total body, and midradius bone mineral densities (BMDs) for various alcohol intakes, compared by analysis of covariance adjusted for smoking, past estrogen use, and other significant covariates (spine BMD was adjusted for smoking status, past estrogen use, height, and weight; femoral neck BMD was adjusted for smoking status, past estrogen use, age, height, and weight; total body BMD was adjusted for smoking status, past estrogen use, height, weight, dietary calcium, and dietary caffeine intakes; midradius BMD was adjusted for smoking status, past estrogen use, age, weight, dietary calcium, and dietary caffeine intakes). *, **Significantly different from nondrinkers (Bonferroni multiple-comparison test): *P < 0.05, **P < 0.01.
Biochemical variables
Calcium absorption and serum variables
Data on calcium absorption, serum variables, and calcitropic hormones of drinkers, nondrinkers, and subjects in various categories of alcohol intake are given in Table 2. Calcium absorption was not significantly different between drinkers and nondrinkers, and the amount of alcohol consumed had no significant effect on calcium absorption. Serum calcium, ionized calcium, phosphorus, alkaline phosphatase, and albumin of drinkers were also not significantly different from those of nondrinkers. Serum ionized calcium was significantly higher in women with an alcohol intake of >28.6 to 57.2 g/wk than in nondrinkers, whereas in other categories of alcohol intake the values were not significantly different from those of nondrinkers. Serum calcium, phosphorus, alkaline phosphatase, and albumin were not significantly different between consumers of different categories of alcohol intake and nondrinkers, except for alkaline phosphatase, which was significantly higher in subjects with an alcohol intake 28.6 g/wk than in nondrinkers. The liver enzyme ALT was not significantly different between the alcohol drinkers and the nondrinkers (0.5 ± 0.03 compared with 0.47 ± 0.01 µkat/L) and between the consumers of different categories of alcohol intake and the nondrinkers (nondrinkers, 0.47 ± 0.01; 28.6 g/wk, 0.49 ± 0.03; >28.6 to 57.2 g/wk, 0.45 ± 0.02; >57.2 to 142.9 g/wk, 0.49 ± 0.03; and >142.9 g/wk, 0.54 ± 0.04 µkat/L).
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TABLE 2. Biochemical variables in drinkers, nondrinkers, and consumers of different categories of alcohol intake1
Calcitropic hormones
Serum 25(OH)D (Table 2) tended to be slightly lower in alcohol consumers than in nondrinkers, but this difference was not significant. On the other hand, serum PTH was significantly lower in alcohol drinkers than in nondrinkers.
When the subjects were categorized into different levels of alcohol intake, serum 25(OH)D tended to be lower in subjects with an alcohol intake of >57.2 to 142.9 g/wk than in nondrinkers (Table 2). Serum 25(OH)D in other categories of alcohol intake was not significantly different from that of nondrinkers. Women with alcohol intakes of >28.6 to 57.2, >57.2 to 142.9, and >142.9 g/wk had lower serum PTH concentrations than did nondrinkers, but only in women with an alcohol intake >28.6 to 57.2 g/wk were the values significantly lower (Figure 2). Serum 1,25(OH)2D concentrations were not significantly different between drinkers and nondrinkers (Table 2) and the amount of alcohol consumed did not significantly influence the serum 1,25(OH)2D concentrations.
FIGURE 2. . Adjusted mean (±SEM) bone marker (osteocalcin and N-telopeptide) and serum parathyroid hormone (PTH) data for alcohol intakes, compared by analysis of covariance adjusted for smoking status, past estrogen use, and other significant covariates (serum osteocalcin and urine N-telopeptides were adjusted for smoking status, past estrogen use, and body weight; serum PTH was adjusted for smoking status, past estrogen use, body weight, dietary calcium, and vitamin D intakes). *Significantly different from nondrinkers, P < 0.05 (Bonferroni multiple-comparison test). NTX:Cr, ratio of urinary cross-linked N-telopeptides of type 1 collagen to creatinine.
Bone markers
Serum osteocalcin, a bone formation marker, was significantly lower in alcohol drinkers than in nondrinkers (3.43 ± 0.160 compared with 4.14 ± 0.126 µg/L, P < 0.001). The bone resorption marker ratio of urinary cross-linked N-telopeptides of type 1 collagen to creatinine (NTX:Cr) was not significantly different between drinkers and nondrinkers (49.14 ± 3.45 compared with 54.35 ± 2.70 nmol BCE/nmol Cr). The bone marker data for various categories of alcohol intake are shown in Figure 2. Women with an alcohol intake of >28.6 to 57.2 g/wk or an intake of >57.2 to 142.9 g/wk had significantly lower serum osteocalcin concentrations (31% and 33%, respectively) than did nondrinkers. Women in alcohol intake categories of >28.6 to 57.2, >57.2 to 142.9, and >142.9 g/wk had lower NTX:Cr (38%, 27%, and 19%, respectively) than did nondrinkers, although not significantly so.
Correlations were run between bone markers, serum PTH, and BMD for the entire study population. A significant positive correlation (although not a very strong one) was observed between PTH and bone remodeling markers (PTH and serum osteocalcin, r = 0.211, P < 0.001; PTH and NTX:Cr, r = 0.11, P < 0.05). There were significant negative correlations (albeit weak) between bone remodeling markers and BMD (total body BMD and serum osteocalcin, r = -0.30, P < 0.001; total body BMD and NTX:Cr, r = -0.32, P < 0.001; spine BMD and serum osteocalcin, r = -0.141, P < 0.01; spine BMD and NTX:Cr, r = -0.140, P < 0.01).
The fasting ratio of urinary calcium to creatinine (Ca:Cr) (Table 2) was not significantly different between drinkers and nondrinkers. However, women with an alcohol intake of >28.6 to 57.2 g/wk had significantly higher excretion of calcium in urine than did nondrinkers (Table 2). Fasting Ca:Cr in other categories of alcohol intake was not significantly different from that of nondrinkers.
DISCUSSION
The results presented in this article provide further evidence for a positive association between BMD and moderate alcohol consumption in elderly postmenopausal women, which is consistent with other published reports (22–25). In addition, we also present evidence that the effect of alcohol can be attributed to reduced bone remodeling.
Laitinen et al (22) first reported a positive correlation between alcohol intake and BMD, with a 12%, 15%, and 9% increase at lumbar spine, Ward's triangle, and femoral neck, respectively, in alcohol drinkers; spine and Ward's triangle values were significant. Feskanich et al (28) observed that women who consumed 75 g alcohol/wk had significantly higher lumbar spine BMD (12%) than did nondrinking women. They also observed a linear increase in spinal BMD over increasing alcohol intakes. However, a similar effect was not found at femoral neck and total hip. Holbrook and Barrett-Connor (26), in a prospective study of men and women, observed that alcohol consumption was associated with an increase in BMD. They reported significant increases in BMD at femur in men and at spine and midradius in women with increasing alcohol intakes (10% increase with alcohol intake of 120 g/wk). In the Framingham study, Felson et al (27) observed that women who drank 200 g alcohol/wk had higher BMD than did those who drank <200 g. They reported 7.5%, 6%, and 4% higher spine, radius, and femoral neck BMD, respectively, in alcohol drinkers; only spine and radius BMD changes were significant. These authors made similar observations in men with high alcohol intakes, although the results were not significant.
In the present study, we observed a significant positive effect of alcohol consumption >28.6 g/wk, which is lower than that reported by earlier researchers. Maximum benefit of alcohol consumption was noted at an intake of >28.6 to 57.2 g/wk. Intakes of >57.2 to 142.9 and >142.9 g/wk also increased BMD but the effect was less than that seen with an intake of >28.6 to 57.2 g/wk. As observed by others, the effect of alcohol was seen primarily at the lumbar spine (ranging from 7% to 16% for various alcohol intakes). In addition, in our study, increasing alcohol intakes increased BMD significantly at the midradius (8–14% for various alcohol intakes) and total body (5–12% at different alcohol intakes). Although femur density was increased by alcohol intake, the effect was not significant, as seen by earlier researchers.
The higher BMD seen in alcohol drinkers in our study could be due mainly to reduction in bone remodeling, as evidenced by the decrease in bone resorption markers, NTX:Cr (19–38% for various alcohol intake categories) and serum osteocalcin (22–31% for various alcohol intake categories). This is the first study that provides direct evidence of decreased bone remodeling markers with moderate alcohol consumption in postmenopausal elderly women.
Although serum osteocalcin is secreted by osteoblasts and is a marker of bone formation, it correlates highly with resorption because formation and resorption are coupled. Serum osteocalcin is increased in diseases with accelerated bone turnover rate (35, 36). In fact, in our study we observed a significant positive correlation between serum osteocalcin and urinary N-telopeptides.
We observed decreased serum PTH concentrations with intakes of alcohol >28.6 g/wk, which could be a cause of the reduced bone resorption. Decreased secretion of PTH hormone was observed with short-term alcohol consumption (37). In addition, Diez et al (38) reported decreased PTH after adjustment for age and sex in 20 men and 6 women with daily intakes of 150 g alcohol for 8 y. In our study, we observed a significant positive correlation between serum PTH and bone markers. The bone markers were in turn negatively correlated with BMD. This further corroborates our notion that the reduced bone remodeling may be due to decreased PTH concentrations.
Other causes of increases in BMD with alcohol consumption that have been suggested are increased serum calcitonin concentrations and increased estrogen concentration. Alcohol is known to stimulate calcitonin production (13), which increases the vertebral BMD without much effect on femoral sites (39, 40). Alternatively, elevation of estrogen concentrations by moderate alcohol consumption may help protect the skeleton. Higher estrogen concentrations have been found in postmenopausal women who consume alcohol (41–43). Thus, the effect of alcohol could also be explained by hormonal factors. The age at menopause in our study subjects was significantly higher in alcohol drinkers than in nondrinkers. Early menopause in women is associated with quantitatively higher bone loss than in women with late-onset menopause (44). It could be argued that the late menopause in alcohol consumers is one of the reasons for the higher BMD observed in these women. However, even after adjustment for age at menopause, alcohol consumption was associated with higher BMD, suggesting that the effect of alcohol was not due to delayed menopause.
In the present study, serum 25(OH)D was found to be marginally lower in subjects consuming >57.2 to 142.9 g alcohol/wk. However, serum 1,25(OH)2D concentrations remained normal in these subjects. A decreased concentration of total 25(OH)D with normal free 25(OH)D has been reported in chronic alcoholism (45). The effect of alcohol intakes of >28.6 to 57.2 g/wk, which is a moderate range, on calcitropic hormones tends to be similar to that seen in chronic alcoholism, although it is marginal. The reason for this observation is not clear. To our knowledge there are no reports of the effect of moderate alcohol consumption on calcitropic hormones in postmenopausal women.
In conclusion, we report a positive association between alcohol consumption and BMD. We also provide substantial evidence indicating that the increase in BMD by alcohol in our elderly population was due mainly to a decrease in bone remodeling. The decreased remodeling may have been due to lowered serum PTH concentrations or may have been mediated through hormonal effects such as higher serum calcitonin concentrations or estrogen concentrations. Although mild to moderate alcohol intake has a protective effect on bone, these results should be viewed with caution because alcohol abuse has apparent untoward effects on bone mineral metabolism.
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