Discussion
In this large, prospective cohort study of middle-aged and older Swedish women, we did not observe an association between coffee consumption and fracture risk. Previous studies on consumption of coffee or intake of caffeine and fracture risk in women have shown discrepant results. Some demonstrate increased risk of fractures with high intakes, whereas others were unable to demonstrate such an association. In contrast to our present results, we have previously observed an increased rate of osteoporotic fractures in women consuming at least 4 cups of coffee per day in a subset of the present cohort. Limitations of our previous analysis, some of which were shared with other studies, were a shorter maximum follow-up time (13 vs. 21 years), a lower number of fracture cases, and, most importantly, incomplete case ascertainment (because we were able to identify only fractures that occurred in the county in which the study was performed). In the present study, we have complete case ascertainment by matching to nationwide inpatient and outpatient registers that include a large number of fractures. Furthermore, we previously were not able to adequately control for lifestyle habits and comorbidity, which could potentially influence the association, although adjustments in our present study did not confer major changes on the estimates.
In our prior analysis, we found that the higher risk of fracture with high coffee intake was concentrated in women with a modest calcium intake. This effect modification was not confirmed in the present analysis. In the SMCC we estimated the associations by vitamin D status. Unexpectedly, we found a somewhat stronger association between coffee intake and BMD among women with vitamin D values higher than 50 nmol/L. A low vitamin D level might reflect frailty, and in the subgroup with low vitamin D values, the association between coffee consumption and bone density might have been overshadowed by factors related to frailty that more strongly influence BMD.
In the majority of studies investigating associations between coffee/caffeine consumption or intake and BMD in women, no association could be demonstrated, whereas such associations have been observed in some studies. Several explanations are possible for the absence of association in these studies, including small study size, low consumption of coffee, or lack of separate assessment of tea and coffee consumption. The small differences in BMD associated with coffee consumption in the present study do not seem to impact the risk of osteoporosis or incident fractures. Importantly, earlier research has shown that the influence of BMD, versus accidental fall–related factors, on fracture rate is more modest in the oldest-old than in young-old individuals. Theoretically, the small decrease in BMD associated with high coffee consumption might be counteracted by a reduced likelihood of hypotension and comorbidities, leading to a lower propensity for injurious falls. The net effect could therefore be no substantial excess risk of fracture. No association between coffee consumption and fall risk was observed in our study, but self-reported falls might not accurately reflect actual injurious falls.
Strengths and Limitations
Several strengths of the study deserve consideration. Because of the high incidence of fractures in our setting, together with a long follow-up, we were able to identify a large number of incident fractures with high accuracy and complete coverage. We were also able to study BMD as a secondary outcome in a large subcohort. The use of repeated FFQs is likely to have reduced measurement error in exposure information. A generally high consumption level in combination with considerable range in the consumption of coffee in this cohort constitutes an additional major strength. Finally, tea consumption is low in this cohort, which might be another advantage in that, for example, the flavonoid compounds in tea could have estrogen-like positive effects on bone.
The study has some weaknesses that should be addressed. Although conclusions about causality cannot be drawn, the prospective design limits the potential for participants to provide selective information because of recall bias or changes in dietary habits due to the fracture event. It might not be possible to generalize the results to women of different ethnic origins or to men. The self-administered questionnaires did not include reference to the size of a cup of coffee, which could have led to misclassification because the volume of a cup can range from 150 to 250 mL (or even larger). Nevertheless, a validation study indicated that the reported coffee consumption seems to be a reasonable estimate of the exposure. Information on caffeinated soft drinks was not available. Consumption of soft drinks (any kind) was low, with 1.4% of the women consuming 1 can of soda or more each day. We did not exclude fractures that were due to high trauma because there are indications of a comparable increased risk of both low- and high-trauma fracture with decreasing bone density in the elderly and because cause-of-injury coding can be inaccurate. However, we were able to analyze time to a second fracture, which theoretically would be a better measure of osteoporotic fracture risk than a single fracture, but no increased risk of fracture was observed.
Although we were able to adjust our associations for several potential covariates, including comorbidities, there still could be residual confounding. Information on smoking and physical activity was available from only the second questionnaire, and data for these variables were imputed for the baseline investigation. However, imputation is less likely to introduce bias than is performance of complete-subject analysis, and our sensitivity analyses without time-updated covariates did not change our conclusions. Finally, a genetic variant of the vitamin D receptor might render carriers more susceptible to the effects of caffeine on bone. Genetically determined differences in the metabolism of caffeine might also be of relevance in this context, but genotyping was not done in the present study.
The lack of increased risk of fractures in our study, even among women consuming high amounts of coffee, is important. This ends a long-running debate about coffee as a potential risk factor for osteoporotic fractures, at least in women.