Introduction
Calcium and vitamin D play important roles in bone health as essential nutrients. Calcium is the most abundant mineral in the body and is involved in many biological processes [
1]. Emphasized by the guidelines, calcium supplementation is commonly taken among the older individuals for the prevention and treatment of osteoporosis [
2‐
4]. However, the association between serum calcium and bone mineral density (BMD) is largely unclear [
5,
6]. Moreover, evidence from previous studies indicated that increased serum calcium correlated with an increased risk of other diseases, such as coronary artery disease and stroke [
7‐
10]. Thus, there is a need to understand the potential effects of serum calcium on bone health and balance potential risks against potential benefits.
On the other hand, vitamin D promotes calcium absorption in the gut and resorption in the kidney and stimulates bone formation and remodeling [
11]. Vitamin D deficiency is associated with decreased calcium absorption [
12]. The relationship of serum 25(OH)D and BMD has been studied extensively over the past decades, but there is still no consensus that higher serum 25(OH)D has positive effects on bone health [
13‐
20].
Worldwide, prevention and treatment of osteoporosis have been two increasingly important public health issues with increasing life expectancy, implying the great need to find more effective ways to reduce the related financial burden [
21,
22]. As a clinically relevant measurement, BMD is commonly used for the diagnosis of osteoporosis and osteopenia. Here, we conducted a cross-sectional study to estimate the associations between serum calcium, 25(OH)D level and lumbar BMD in older adults using a large-scale database from National Health and Nutrition Examination Survey (NHANES).
Discussion
In this study, we used these representative samples of NHANES 2001–2006 to evaluate the associations between serum calcium, 25(OH)D and lumbar BMD in older adults. The results revealed a negative association between serum calcium and lumbar BMD, and a positive association between serum 25(OH)D and lumbar BMD. Specifically, the association between serum calcium and lumbar BMD in males followed a U-shaped curve. For males, lumbar BMD increased with serum calcium up to the turning point (9.6 mg/dL).
Despite the fact that calcium is the primary nutrient of interest in bone health, the information from previous studies linking serum calcium and BMD is limited. Recently, Cerani et al. [
5] conducted a Mendelian randomization study, their data suggested that increased serum calcium levels did not increase BMD or provide clinically relevant protection against fracture. In a longitudinal cohort study consisting of 381 participants conducted by Dalemo et al. [
6], the results revealed there was no correlation between baseline calcium and BMD at follow-up. Their data also showed patients with elevated serum calcium levels at baseline had osteoporosis more often than controls 10 years later. In the present study, we found a negative association between serum calcium and lumbar BMD. According to the STROBE statement [
26], we use subgroup analysis to make better use of the data. In the subgroup analysis, this association was no longer significant among males and other race/ethnicity.
In the NHANES III study (1988–1994), Heike et al. [
19] found the serum 25(OH)D positively correlated with the total hip BMD in older adults, and this association was strongest in whites. Some other cross-sectional studies supported this positive association of 25(OH)D with BMD [
18‐
20]. Recently, Sun et al. [
13] performed a Mendelian randomization study to investigate the association between vitamin D levels and total BMD, and their data showed increased vitamin D could not improve BMD in the general population. Our finding was consistent with the NHANES III study [
19]. The strongest association between 25(OH)D and lumbar BMD was in whites, and this association followed a U-shaped curve in Mexican Americans. Therefore, the reasons for these different conclusions may be the heterogeneity among studies, including study size, study design, and differences in participant selection, such as age, sex, and race/ethnicity. Nevertheless, our results supported that increased 25(OH)D level would be beneficial to bone health in the population with 25(OH)D deficiency.
The representative samples of the multiracial population are included in this study to better generalize of the US population, and this large sample size allowed us to perform further subgroup analyses. This is the biggest strength of this study. There are some limitations. First, due to the nature of the cross-sectional study, we cannot determine whether higher vitamin D levels or lower serum calcium influence change in BMD over time, and the causality cannot be assessed. Second, we excluded participants with cancer or malignancy because these special populations have a great influence on serum calcium and BMD. Thus, the conclusions in this study cannot be used for them. Third, we did not adjust other variables. Therefore, the bias caused by other potential confounding factors is not excluded.
Conclusions
In conclusion, our results suggested that serum calcium negatively correlated with lumbar BMD, and serum 25(OH)D positively correlated with lumbar BMD in older adults. However, the association between serum calcium and lumbar BMD in males followed a U-shaped curve.
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