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Smoking Increases Bone Loss and Decreases Intestinal Calcium Absorption
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Journal of Bone and Mineral Research, February 1999
Elizabeth A. Krall, 1,2 Bess Dawson-Hughes1
1Calcium and Bone Metabolism Laboratory, Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, Boston, Massachusetts, U.S.A.
2Department of Health Policy and Health Services Research, Boston University Goldman School of Dental Medicine, Boston, Massachusetts, U.S.A.
ABSTRACT
Cigarette use is a risk factor for increased bone mineral density (BMD) loss but the mechanisms are not well understood. The relationship of smoking to rates of BMD change at the femoral neck, spine, and total body, and to intestinal calcium absorption were examined in 402 elderly men and women (32 smokers, 370 nonsmokers) who participated in a 3-year placebo-controlled study of calcium and vitamin D supplementation. Subjects in the supplemented group took 500 mg/day of elemental calcium and 700 IU/day of cholecalciferol. Two-hour calcium absorption fraction was determined three times, at 18, 30, and 36 months, with a single isotope method utilizing45Ca in a subset of 333 subjects. Annualized rates of BMD loss (adjusted for baseline BMD, weight, age, gender, supplementation status, and dietary calcium intake) were higher in smokers than nonsmokers at the femoral neck (-0.714 ± 0.285 %/year vs. +0.038 ± 0.084 %/year, p < 0.02), and total body (-0.360 ± 0.101 %/year vs. -0.152 ± 0.030 %/year, p < 0.05). No significant difference was observed at the spine (+0.260 ± 0.252 %/year in smokers vs. +0.593 ± 0.074 %/year in nonsmokers, p = 0.21). The mean (± SEM) calcium absorption fraction was lower in smokers (12.9 ± 0.8%, n = 23) than nonsmokers (14.6 ± 0.2%, n = 310, p < 0.05) after adjustment for gender, age, supplementation status, and dietary calcium and vitamin D intakes. Smokers of at least 20 cigarettes per day (n = 15) had the lowest mean absorption fraction (12.1 ± 1.1%). With calcium and vitamin D supplementation, the proportionate increase in urinary calcium/creatinine excretion was lower in smokers (44 ± 12%) than nonsmokers (79 ± 9%, p < 0.05). These results suggest that smoking accelerates bone loss from the femoral neck and total body in the elderly and that less efficient calcium absorption may be one contributing factor.
INTRODUCTION
CIGARETTE USE HAS BEEN IDENTIFIED as a risk factor for low bone mineral density (BMD) and osteoporotic fracture.1-7 Longitudinal studies indicate that rates of bone loss are approximately one-and-a-half to two times greater if one is a current smoker.8-10 However, the biological mechanisms by which smoking, or components of cigarette smoke, influence BMD and bone loss are not well understood. They may include local and systemic toxic effects on bone collagen synthesis, alterations in metabolism of adrenal cortical and gonadal hormones,12-14 and other undetermined mechanisms.
An additional contributing factor may be decreased calcium absorption efficiency among smokers.8,15 In an earlier study, we observed a lower calcium absorption fraction among women who currently smoked compared with nonsmokers.8 Limitations of that study included the small number of smokers who had undergone the calcium absorption test and the fact that men were excluded from the study population. In the present analysis, we sought to replicate those earlier findings in a larger group of subjects that included men as well as women. Intestinal calcium absorption, urinary calcium excretion, and longitudinal rates of BMD change were examined in relation to smoking status among elderly adults participating in a nutritional supplementation trial.
DISCUSSION
The findings in this group of elderly men and women further strengthen the evidence that cigarette smoking increases the rate of bone loss. Previous studies of postmenopausal women reported associations between current cigarette use and increased rate of bone loss from the radius8 and hip.10 Greater bone loss from the radius was observed in males who smoke,2,17 particularly among those who smoke more than one pack per day.17 In the present study, there was no indication that the influence of smoking on bone loss at the femoral neck and total body differed by gender. A similar trend was observed at the spine. The apparent increase in BMD at this site can probably be attributed to vascular and other calcifications in the spine scan field. The pattern of net gain in spine BMD was reported previously in this study population in relation to calcium and vitamin D supplementation.16
We were not able to detect statistically significant differences in baseline BMD by smoking status. The strength of an association between smoking and cross-sectional BMD measurements will depend on variations in duration and dose over a long period of time and perhaps the age at which smoking began. We did not have complete information on these variables. Genetic predisposition and a large number of lifestyle factors that act throughout adulthood also influence an individual's BMD in later life. Prospective rates of bone loss offer stronger evidence for a biological association than cross-sectional BMD measurements.
Both the45Ca absorption data and urinary calcium excretion data support the hypothesis that smokers do not absorb dietary or supplemental calcium as efficiently as nonsmokers. Once supplementation began, urinary calcium excretion exhibited the sharp and sustained increase that is expected when calcium intake is suddenly increased. However, the smokers responded less efficiently than nonsmokers. At an average intake of 1200 mg/day, a 1.7% reduction in calcium absorption due to smoking would result in 20 mg/day less calcium available to the body. This absorption index used in our laboratory18 is not a measure of true absorption and can not be directly compared with other absorption methods. However, it does have excellent reproducibility and a strong linear correlation with true absorption values obtained from the more elaborate double isotope and balance methods.19,20
Lower calcium absorption in smokers may be one pathway by which smoking affects the rate of bone loss. However, the mechanism is still not clear. There is evidence from animal studies to suggest that some component of cigarette smoke damages intestinal villi.21 Nicotine is known to have vasoconstrictive action. However, the subjects did not smoke during the absorption test, and thus little or no nicotine effect on the intestinal blood supply would be expected. Nicotine metabolites such as cotinine remain in the body for 24-36 h after smoking abstinence. Although cotinine is thought to have minimal effect on certain cardiovascular measures,22,23 it is not known if it results in a modest reduction in intestinal blood flow that might explain the calcium absorption findings. Nevertheless, it is unlikely that reduced calcium absorption accounts for the total difference in bone loss rate between smokers and nonsmokers.
Cigarette smoking has widespread effects on the body that may decrease calcium absorption and independently influence bone metabolism. Smoking has been reported to alter circulating levels of adrenal cortical hormones that are precursors of estrogen and testosterone, but studies are conflicting as to whether smokers have increased or decreased levels of serum cortisol, androstenedione, dehydroepiandrosterone (DHEA), dehydroepiandrosterone sulfate (DHEAS), and sex steroids.12,14,24,25 Estrogen deficiency is associated with lower calcium absorption efficiency, which can be restored with estrogen replacement.26 Although men and postmenopausal women who smoke may have higher serum steroid levels, the expected benefit to bone tissue and calcium absorption may be offset by more rapid hyroxylation.13
Limitations of the present study include the small number of current smokers. The subjects were a healthy subset of the elderly population. Although smoking was not an exclusion for this trial, subjects with serious chronic illness were less likely to be enrolled in the trial and smokers have a higher prevalence of serious illnesses than nonsmokers. Another limitation is the lack of data on hormone levels, which might have helped to better explain the differences in bone loss and calcium absorption in smokers and nonsmokers.
In conclusion, this study found cigarette use to be a risk factor for accelerated bone loss in elderly men and women. One contributing factor appears to be lowered intestinal calcium absorption efficiency, but more research is needed to understand fully the biologic mechanisms that result in greater bone loss among smokers.
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