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The Journal of Nutrition logoLink to The Journal of Nutrition
. 2023 May 9;153(9):2642–2650. doi: 10.1016/j.tjnut.2023.05.009

Association between a Calcium-to-Magnesium Ratio and Osteoporosis among Puerto Rican Adults

Liam E Fouhy 1,2, Kelsey M Mangano 1,2, Xiyuan Zhang 2, Bess Dawson Hughes 3, Katherine L Tucker 1,2, Sabrina E Noel 1,2,∗
PMCID: PMC10550845  PMID: 37164266

Abstract

Background

The ratio of calcium-to-magnesium intake (Ca:Mg) may be important for bone due to their competitive absorption. The Ca:Mg ratio has been related to health outcomes, but few studies have related it to bone.

Objectives

The purpose of this analysis was to examine associations between the Ca:Mg intake with bone mineral density (BMD) and osteoporosis among Puerto Rican adults.

Methods

Adults, aged 47–79 y, from the Boston Puerto Rican Osteoporosis Study, with complete BMD and dietary data (n = 955) were included. BMD was assessed with dual-energy X-ray absorptiometry and diet by a food frequency questionnaire. Calcium and magnesium intakes from food were energy adjusted, and the Ca:Mg was calculated. Adjusted linear and logistic regression models were utilized for testing associations between Ca:Mg and bone outcomes.

Results

Calcium intake was greater in the highest compared with lowest tertile, whereas magnesium intake was similar across tertiles. Mean BMD at hip sites was higher in the middle, compared with the lowest, tertile. Higher odds of osteoporosis were observed for the highest and lowest tertiles, compared with the middle tertile, after adjustment (T3 compared with T2 OR: 2.79; 95% CI: 1.47, 5.3; T1 compared with T2 OR: 2.01; 95% CI: 1.03, 3.92). Repeated analyses without supplement users (n = 432) led to stronger differences and ORs, but lost significance for some comparisons.

Conclusions

Dietary calcium and magnesium are important for bone, perhaps not independently. The Ca:Mg intake ratio appeared most protective within a range of 2.2–3.2, suggesting that a balance of these nutrients may be considered in recommendations for osteoporosis..

Keywords: osteoporosis, calcium, magnesium, health disparities, aging

Introduction

Dietary calcium and magnesium facilitate many physiological processes within the body and are important for maintaining bone health [1, 2, 3]. Calcium plays a major role in providing strength and structure to bone [4]. Magnesium impacts bone by affecting actions of PTH and 1,25 (OH)2-vitamin D, which are major regulators of calcium homeostasis [5]. Calcium and magnesium are considered “shortfall” nutrients, as many adults do not meet intake recommendations. In the United States, mean daily intakes of adults aged 20 y and older have been estimated for calcium as 1083 mg for men and 842 mg for women, relative to recommendations of 1200 mg/d; and for magnesium as 342 mg for men and 269 mg for women, relative to recommendations of 420 and 320 mg/d, respectively [6].

Many studies have shown that dietary calcium intake is protective for bone [7, 8, 9, 10]. However, a recent systematic review found that increasing the calcium intake through dietary or supplemental sources resulted in only small increases in BMD (0.6%–1.8%) over 2 y [11]. Magnesium from food and supplements has also been associated with higher BMD in epidemiologic cohort studies [12,13] and clinical trials [14,15] but, compared with calcium and vitamin D, has been understudied in bone research. Inconsistent findings across studies may be due to a lack of consideration of the complex interactions between calcium and magnesium. Calcium and magnesium compete for absorption [2,16, 17, 18, 19] such that excess calcium not only blocks entry of magnesium into gut endothelial cells but also increases excretion of magnesium through the kidneys [1,20,21]. Because of the complex interrelationship between these nutrients, several studies have investigated associations between a calcium-to-magnesium ratio (Ca:Mg) and chronic conditions such as CVD [22], metabolic syndrome [23], cancer [24,25], and cancer mortality [26,27]. These studies have included non-Hispanic White [28], non-Hispanic Black [29], Mexican American [29], native Japanese [30], and native Chinese populations [31]. Findings suggest that the optimal Ca:Mg ratio may be population- and outcome-specific [29,31,32]. To our knowledge, no studies have examined the relationship between Ca:Mg and bone outcomes, and none among Caribbean Latino adults, regardless of the outcome.

Puerto Rican men and women have been shown to have similar or higher prevalence of osteoporosis, compared with non-Hispanic White and Mexican American men and women, aged 50 y and older [33]. Despite being at an increased risk, few studies have identified risk factors for bone health that could be used to inform recommendations and future prevention strategies. Understanding relationships between dietary calcium and magnesium may be important for guiding dietary recommendations for this population. This study aimed to examine cross-sectional associations between dietary calcium, magnesium, and the Ca:Mg ratio with BMD and osteoporosis in a cohort of Puerto Rican adults residing in the Greater Boston area. To our knowledge, this is one of the first studies examining the Ca:Mg ratio in relationship to bone health. The ratio may be important for bone, given the complex physiologic relationship between calcium and magnesium.

Methods

Study design

The Boston Puerto Rican Osteoporosis Study (BPROS) is ancillary to the Boston Puerto Rican Health Study (BPRHS), a cohort of 1499 Puerto Rican adults aged 45–75 y recruited from the Greater Boston area. The study design and methodology for the parent cohort have been described elsewhere [33]. Inclusion criteria were as follows: 1) those who self-identified as Puerto Rican, 2) aged 45–75 y, and 3) lived in the Greater Boston area with no plans to move within 2 y for participation in follow-up visits. Individuals who had a Mini Mental State Examination Score ≤10 or were unable to answer questions due to a serious health condition were excluded [34]. Participants in the BPRHS completed interviews at baseline and ∼2–3 y follow-up in their homes by trained bilingual interviewers to collect data, which include sociodemographic variables, health and health behaviors, dietary intake, medication use, and anthropometric measures. Participants who completed 2–3 y follow-up (n = 1267) were invited to participate in the BPROS. A total of 973 chose to participate and completed an additional interview and BMD measures at the USDA research laboratory at Tufts Medical Center. The current analysis included participants with complete data for BMD of the lumbar spine (L2–L4) and femoral neck, anthropometric measures, sociodemographic information, health behaviors, and dietary intake (Figure 1). Those who declined participation in the BPROS were older (60.9 y compared with 58.7 y, P < 0.001) and were more likely to have type II diabetes (47.8% compared with 40.4%, P < 0.03) compared with those who participated in the ancillary follow-up. The final analytic sample included 849 participants. This study was approved by the Institutional Research Boards at Tufts University, Northeastern University, and the University of Massachusetts Lowell.

FIGURE 1.

FIGURE 1

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Participant flowchart from Boston Puerto Rican Health Study. BPROS, Boston Puerto Rican Osteoporosis Study.

Osteoporosis ascertainment

BMD of the hip and lumbar spine was measured by DXA (GE Lunar Model Prodigy scanner, GE Lunar; DXA acquisition software version 6.1 and analysis version 12.2) at the Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University (root-mean-square precision was 1.2% for BMD measures of the lumbar spine and 0.9% for femoral neck) [35]. The right hip was scanned unless the participant reported having a previous hip fracture or joint replacement. The stability of DXA measurements was assessed weekly using an external standard (aluminum spine phantom; Lunar Radiation Corp). Osteoporosis was defined as a T-score ≤−2.5 (2.5 SD or more below peak bone mass) at the femoral neck and/or lumbar spine (L2–L4) [36]. Lumbar spine T-scores were estimated using a reference group of 30 y old non-Hispanic White females from the DXA manufacturer database [37] and femoral neck T-scores from a reference group of 20–29 y old non-Hispanic White females from NHANES III [38].

Dietary assessment

Usual dietary intake over the past 12 mo was assessed during the BPRHS 2–3 y follow-up visit using a semiquantitative FFQ. The FFQ was modified from the NCI-Block FFQ for use in this population [39] and has been validated against plasma carotenoids [40], vitamin E [41], and vitamin B12 [42] in Puerto Rican adults [39]. Participants who reported energy intake <600 or >4800 kilocalories and/or failed to answer 10 or more questions from the FFQ were excluded. Nutrient analysis was completed using the Nutrient Data System for Research Software (NDS-R, Nutrition Coordinating Center, University of Minnesota) to obtain usual daily nutrient intakes. Dietary calcium and magnesium (from foods) were adjusted for the total energy intake using the residual method [43]. After adjustment, total dietary calcium from food sources was divided by total dietary magnesium from food sources to calculate a continuous ratio, which was subsequently categorized into tertiles. This ratio was calculated from food sources only, and supplement intake was later adjusted for in the models and supplement users were totally removed in supplementary reverse causation analysis.

Covariates

Sociodemographic data, including age and sex, were assessed through a questionnaire. Sex, age, and estrogen status are known risk factors for bone loss [44]. Anthropometric measures, including height and weight, were obtained using standard procedures [45], and BMI was calculated as weight (kg) divided by height (m) squared. Health behaviors, including smoking and alcohol consumption, were ascertained through a questionnaire at the 2–3 y BPRHS follow-up visit. Smoking has been inversely associated with bone health [46]. Moderate alcohol intake has been associated with higher BMD, whereas heavy drinking (>2 drinks/d for women or >3 for men) has been associated with significantly lower BMD [47]. Dietary supplement use was captured from the FFQ, as well as the over-the-counter medication section of the BPRHS questionnaire. On the basis of the distribution of magnesium and calcium supplement use in this population, magnesium supplement use was defined as a binary variable [nonsupplement users (0 mg/d) or supplement users (>0 mg/d)] and calcium supplement use as 3 categories (0, 0–300, or >300 mg/d).

The serum 25(OH)D concentration was measured by extraction followed by RIA with a 25I radioimmunoassay Packard COBRA II Gamma Counter (catalog no. 68100E; DiaSorin, Inc) with intra-assay and inter-assay CVs of 10.8% and 9.4%, respectively. For women only, the use of estrogen medication either orally or by patch (not including vaginal cream) was obtained, including Premarin, Prempro, Premphase, Estratab, Menest, Estrace, Ogen (Ortho-est), Estraderm (Vivelle), Evista, and/or other medications. Data on menopausal status (yes or no) and estrogen medication use (yes or no) were used to classify women as exposed to estrogen (premenopausal or taking estrogen medications) or not (postmenopausal and not taking estrogen medications).

Statistical analysis

All analyses were conducted using SAS software (version 9.4, SAS Institute). All variables were examined for normality. Means (SD) and frequencies for sociodemographic, and health and health behaviors, and bone outcomes were compared across tertile categories using analysis of covariance for means and chi-square for frequencies. P-trend tests were performed. Multivariable general linear models were used to calculate adjusted least squares means and SE of BMD for each anatomical site (lumbar spine, femoral neck, trochanter, and total hip) across tertiles of Ca:Mg. Tukey’s test was used to adjust for multiple comparisons. Multivariable logistic regression was used to model associations between Ca:Mg and osteoporosis (yes/no) at the femoral neck and/or lumbar spine. Models were adjusted for age (y), sex/estrogen status, height (m), BMI (kg/m2), smoking status (never, past, or current), alcohol consumption (none, moderate, or heavy), serum 25(OH)D (ng/dL), use of magnesium supplements (yes/no), and use of calcium supplements (none, 0–300, and ≥300 mg). Because of the collinearity between dietary calcium and magnesium (r = 0.82), model 2 was further adjusted only for dietary magnesium, model 3 for dietary calcium, and model 4 for dietary calcium and magnesium simultaneously; all models were a priori and based on collinearity between dietary calcium and magnesium intakes. Physical activity was originally included as a covariate but showed no association with the outcome and, therefore, was subsequently removed. Interactions between Ca:Mg and sex/estrogen status and Ca:Mg and 25(OH)D [sufficient (≥20 ng/mL) or insufficient (<20 ng/mL)] [48] were tested but were not statistically significant (both P > 0.25). In sensitivity analyses and to examine for potential reverse causation, all models examining associations between Ca:Mg and bone outcomes were repeated, excluding participants who reported using calcium and/or magnesium supplements (n = 432).

Results

Mean dietary calcium intake was significantly higher in the highest, compared with the lowest, Ca:Mg tertile (1141 ± 296 mg compared with 704 ± 153 mg, P-trend < 0.001), whereas magnesium intake remained constant across ratio tertiles (P = 0.58) (Table 1). Participants in the highest Ca:Mg ratio tertile had a higher serum 25(OH)D concentration than those in the lowest tertile (21.0 ± 7.2 ng/dl compared with 18.1 ± 7.4 ng/dl, P-trend < 0.001). The frequency of heavy alcohol consumption was lower in the highest compared with lowest Ca:Mg tertile (2.4% compared with 7.1%, P-trend = 0.02). Calcium use and magnesium supplement use were most common in the highest compared with lowest tertile of Ca:Mg (24.3% compared with 15.9%, P-trend = 0.01 and 43.2% compared with 31.4%, P-trend = 0.01, respectively). Osteoporosis was more prevalent in both the highest and lowest Ca:Mg ratio tertiles, relative to the middle tertile (13.2% and 10.1% compared with 6.7%, respectively; P-trend = 0.03). There were no significant differences in age, height, BMI, dietary magnesium intake, BMD at spine or hip sites, smoking status, or sex/estrogen status across Ca:Mg tertiles.

TABLE 1.

Sociodemographic and descriptive data by tertile of dietary Ca:Mg ratio among Puerto Rican adults (n = 888)1

Characteristic
 Calcium-to-magnesium intake ratio (Ca:Mg)
Tertile 1 (n = 296)
 Tertile 2 (n = 296)
 Tertile 3 (n = 296)
Mean (SD)/% Mean (SD)/% Mean (SD)/% P-trend
Age (y) 59.9 (7.6) 60.3 (7.5) 59.8 (7.8) 0.89
Height (cm) 159 (8.5) 158 (8.2) 158 (8.4) 0.47
BMI (kg/m2) 32.4 (7.0) 32.2 (6.4) 32.1 (6.2) 0.19
Dietary calcium (mg) 704 (153) 890 (151) 1141 (296) <0.001
Dietary magnesium (mg) 316 (56) 317 (50) 319 (61) 0.58
Ca:Mg ratio 2.2 (0.3) 2.8 (0.1) 3.6 (0.5) <0.001
Serum vitamin D (ng/dL) 18.1 (7.4) 19.7 (7.0) 21.0 (7.2) <0.001
BMD femoral neck 0.93 (0.15) 0.95 (0.14) 0.92 (0.15) 0.38
BMD lumbar spine 1.17 (0.19) 1.18 (0.19) 1.15 (0.19) 0.14
BMD femur trochanter 0.82 (0.14) 0.84 (0.14) 0.81 (0.15) 0.51
BMD total hip 1.02 (0.16) 1.05 (0.16) 1.01 (0.16) 0.36
Years in United States 22.2 (12.0) 23.3 (12.6) 23.5 (11.6) 0.52
Osteoporosis (%) 10.1 6.7 13.2 0.03
Alcohol consumption (%)
 None in past year 64.4 65.7 70.5 0.02
 Moderate 28.5 31.6 27.2
 Heavy 7.1 2.7 2.4
Smoking status (%)
 Never (<100 cigarettes in life) 42.2 49.7 45.2 0.27
 Smoked in the past 33.7 32.8 34.7
 Current smoker 24.2 17.6 20.1
Estrogenic status (%)
 Men 32.2 23.4 26.8 0.14
 Premenopausal women or taking estrogen 11.2 10.0 10.2
 Postmenopausal women not taking estrogen 56.6 66.7 63.1
Calcium supplement use (%)
 None 55.4 48.7 42.2 0.01
 0–300 mg 28.7 28.0 33.5
 ≥300 mg 15.9 23.3 24.3
Magnesium supplement use (%)
 Yes 31.4 34.1 43.2 0.01
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Analysis of variance and chi-square analyses were conducted to examine differences in means (SD) and percentages across tertiles of Ca:Mg intake ratio. P-trends across tertiles are presented.

In models adjusted for dietary magnesium (Figure 2, Table 2, model 2), mean BMD at all hip sites was higher in the middle than the lowest tertile of the Ca:Mg intake ratio (femoral neck: 0.972 ± 0.01 g/cm2 compared with 0.940 ± 0.01 g/cm2; trochanter: 0.859 ± 0.01 g/cm2 compared with 0.830 ± 0.01 g/cm2; and total hip: 1.063 ± 0.012 g/cm2 compared with 1.026 ± 0.01 g/cm2, respectively). Mean BMD was also higher in the middle Ca:Mg tertile than that in the highest tertile for the trochanter (0.859 ± 0.010 g/cm2 compared with 0.833 ± 0.010 g/cm2) and total hip (1.063 ± 0.012 g/cm2 compared with 1.031 ± 0.012 g/cm2). Similarly, in models adjusted for dietary calcium (Table 2, model 3), mean BMD was highest in the middle tertile compared with the lowest Ca:Mg tertile for the femoral neck (0.972 ± 0.01 g/cm2 compared with 0.943 ± 0.012 g/cm2, P = 0.03) and total hip (1.063 ± 0.012 g/cm2 compared with 1.032 ± 0.013 g/cm2, P = 0.03). Mean BMD was also significantly higher in the middle tertile compared with the highest tertile of the Ca:Mg ratio for all hip and spine sites (femoral neck: 0.972 ± 0.011 g/cm2 compared with 0.936 ± 0.012 g/cm2, P = 0.01; lumbar spine: 1.21 ± 0.015 g/cm2 compared with 1.19 ± 0.016 g/cm2, P = 0.05; trochanter: 0.86 ± 0.011 g/cm2 compared with 0.827 ± 0.011 g/cm2, P = 0.01; and total hip: 1.063 ± 0.012 g/cm2 compared with 1.02 ± 0.013 g/cm2, P = 0.003). Similar associations were noted when models were adjusted for both calcium and magnesium (Table 2, model 4). After adjustment for Ca:Mg, dietary magnesium intake was associated with higher BMD at the trochanter (B: 0.02 g/cm2 ± 0.008, P = 0.008) and the total hip (B:0.02 g/cm2 ± 0.009, P = 0.009), but not at the femoral neck (P = 0.27), but approached significance at the lumbar spine (P = 0.07). Dietary calcium was not associated with BMD at any of the sites (range of P values: 0.34–0.61).

FIGURE 2.

FIGURE 2

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Mean (±SE) BMD at hip and lumbar spine sites by tertile of Ca:Mg ratio. Means with different superscript letters are significantly different at α < 0.05. Model was adjusted for age, estrogen status, height, BMI, smoking status, alcohol intake, use of calcium supplements, use of magnesium supplements, and dietary magnesium. Red indicates tertile 1, blue indicates tertile 2, and green indicates tertile 3. Ca:Mg, calcium-to-magnesium ratio.

TABLE 2.

Adjusted mean BMD at hip and spine sites across dietary Ca:Mg tertiles among Puerto Rican adults (n = 888)1

BMD at spine and hip sites Calcium-to-magnesium intake ratio (Ca:Mg)
Tertile 1 (n = 296)
 Tertile 2 (n = 296)
 Tertile 3 (n = 296)
Mean ± SD Mean ± SD Mean ± SD
Lumbar spine (L2–L4) BMD (g/cm2)
 Model 1 1.180 ± 0.015 1.204 ± 0.015 1.172 ± 0.015
 Model 2 1.180 ± 0.015 1.210 ± 0.015 1.172 ± 0.015
 Model 3 1.190 ± 0.016 1.211 ± 0.0151 1.170 ± 0.0162
 Model 4 1.170 ± 0.018 1.204 ± 0.015 1.180 ± 0.018
Femoral neck BMD (g/cm2)
 Model 1 0.940 ± 0.011 0.971 ± 0.0112 0.938 ± 0.0111
 Model 2 0.940 ± 0.011 0.972 ± 0.0112 0.939 ± 0.011
 Model 3 0.943 ± 0.0121 0.972 ± 0.0112 0.936 ± 0.0121
 Model 4 0.936 ± 0.0131 0.971 ± 0.0112 0.943 ± 0.013
Trochanter BMD (g/cm2)
 Model 1 0.830 ± 0.011 0.858 ± 0.0112 0.833 ± 0.0111
 Model 2 0.830 ± 0.011 0.859 ± 0.0112 0.833 ± 0.0111
 Model 3 0.836 ± 0.011 0.86 ± 0.0112 0.827 ± 0.0111
 Model 4 0.825 ± 0.0131 0.858 ± 0.0112 0.838 ± 0.013
Total hip BMD (g/cm2)
 Model 1 1.025 ± 0.0111 1.062 ± 0.0122 1.025 ± 0.0121
 Model 2 1.026 ± 0.0111 1.063 ± 0.0122 1.031 ± 0.0121
 Model 3 1.032 ± 0.0131 1.063 ± 0.0122 1.020 ± 0.0131
 Model 4 1.017 ± 0.0141 1.061 ± 0.0122 1.033 ± 0.014
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Means with different superscript numbers are significantly different. Model 1 was adjusted for age, sex/estrogen status, height, BMI, smoking status, serum vitamin D concentration, alcohol intake, use of calcium supplements, and use of magnesium supplements. Model 2 was adjusted for model 1 plus dietary magnesium. Model 3 was adjusted for model 1 plus dietary calcium. Model 4 was adjusted for model 1 plus dietary calcium and dietary magnesium.

After excluding supplement users, the middle Ca:Mg tertile, compared with the lowest, was associated with higher mean BMD (1.236 g/cm2 compared with 1.167 g/cm2) only in the fully adjusted model (Supplemental Table 1). At the femoral neck and trochanter, BMD was significant higher for the middle Ca:Mg tertile compared with the lowest tertile in all models. At the total hip, BMD was higher for the middle compared with lowest and the lowest and highest tertiles in models 1 and 2, but after adjustment for total calcium intake, the highest tertile was no longer significant.

In models adjusted for dietary magnesium, the highest and lowest Ca:Mg tertiles, compared with the middle (reference group), were associated with a higher likelihood of osteoporosis [Q3 compared with Q2 (ref) OR: 2.79; 95% CI: 1.47, 5.3; and Q1 compared with Q2 (ref) OR: 2.01; 95% CI: 1.03, 3.92 respectively, Figure 3, Table 3, model 2]. Similar results were observed for models adjusted for dietary calcium or dietary calcium and dietary magnesium; however, associations between the lowest and middle Ca:Mg tertiles were no longer statistically significant (Table 3, models 3 and 4).

FIGURE 3.

FIGURE 3

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OR and 95% CIs for the association between lowest compared with. middle (reference group) and highest compared with. middle (reference group) Ca:Mg intake ratio and osteoporosis. Model 1 was adjusted for age, estrogen status, height, BMI, smoking status, alcohol intake, use of calcium supplements, and use of magnesium supplements. Model 2 was adjusted for model 1 plus dietary magnesium. Model 3 was adjusted for model 1 plus dietary calcium. Model 4 was adjusted for model 1 plus dietary calcium and dietary magnesium. Ca:Mg, calcium-to-magnesium ratio; Ref, reference.

TABLE 3.

OR and 95% CI of osteoporosis for the lowest compared with middle (reference) and highest compared with middle (reference) tertile of Ca:Mg intake ratio among Puerto Rican adults (n = 888)1

Ca:Mg tertile OR 95% CI
Model 1
 Tertile 0 vs. 1 1.93 1.00, 3.74
 Tertile 2 vs. 1 2.58 1.36, 4.87
Model 2
 Tertile 0 vs. 1 2.01 1.03, 3.92
 Tertile 2 vs. 1 2.79 1.47, 5.30
Model 3
 Tertile 0 vs. 1 1.59 0.80, 3.20
 Tertile 2 vs. 1 3.59 1.75, 7.37
Model 4
 Tertile 0 vs. 1 2.02 0.96, 4.25
 Tertile 2 vs. 1 2.78 1.26, 6.12
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Model 1 was adjusted for age, sex/estrogen status, BMI, height, serum vitamin D concentration, alcohol consumption, smoking status, and calcium supplement and magnesium supplement use. Model 2 was adjusted for model 1 plus dietary magnesium. Model 3 was adjusted for model 1 plus dietary calcium. Model 4 was adjusted for model 1 and dietary calcium and magnesium intake.

After excluding supplement users, the ORs for the relationship between Ca:Mg and osteoporosis were stronger [lowest compared with middle tertile (OR: 3.26; 95% CI: 1.00, 10.6) and highest compared with middle tertile (OR: 3.60; 95% CI: 1.08, 11.9)] (Supplemental Table 2, model 1). In model 2, which included adjustment for total dietary magnesium intake, the highest, compared with middle, tertile of Ca:Mg was associated with higher odds of osteoporosis (OR: 3.67; 95% CI: 1.10, 12.2) (Supplemental Table 2, model 2). In model 4, additionally adjusted for dietary calcium and magnesium intake, the lowest Ca:Mg compared with the middle tertile was associated with a higher likelihood of osteoporosis (OR: 3.76; 95% CI: 1.04, 13.7).

Discussion

Our findings indicate that the middle tertile of Ca:Mg (ratio: 2.8) was associated with a lower likelihood of osteoporosis and higher BMD, compared with the highest or lowest Ca:Mg tertiles among Puerto Rican adults. These findings suggest that there may be an optimal ratio for dietary calcium in relation to magnesium intake to optimize bone health. Specifically, when calcium intake is below 2.2 times or exceeds 3.2 times that of magnesium, it appears to be associated with poorer bone outcomes. This may be because of issues with absorption of these key nutrients impacting bone turnover [49].

Our findings are consistent with studies of other chronic conditions such as colorectal cancer [50], prostate cancer [25], breast cancer [26], CVD [51], and all-cause mortality [31], indicating that a balance between calcium and magnesium is important for health outcomes. The majority of these studies suggested that Ca:Mg between 1.7 and 3.0 may be protective of colorectal cancer [24], prostate cancer [28], all-cause mortality [31], and CVD mortality [30]. Interestingly, for CVD mortality [30] and breast cancer mortality [26], the Ca:Mg was more important than meeting the RDA for either nutrient. In a case-control study, a higher intake of magnesium was associated with a reduced risk of colorectal adenoma, but this was only the case for those with a Ca:Mg ratio ≤2.78, suggesting that excess calcium in relation to magnesium may be detrimental [50]. Similarly, a population-based study in China found that a Ca:Mg ratio above 1.7 was associated with an increased risk of total mortality for men, but for women, with a ratio ≤1.7, intake of magnesium was associated with an increased risk of total mortality and mortality due to colorectal cancer [31]. The inconsistencies across studies may be due to differences in dietary intakes by geographic locations and cultural dietary behaviors. For example, the beneficial range of Ca:Mg for an East Asian population was relatively low (1.7) likely because of the fact that typical dietary patterns for Chinese and Japanese populations contain fewer dairy products. Conversely, studies of Ca:Mg in the United States typically had higher ratios (2.6–3.0) as protective of certain health conditions [30]. Several studies have speculated that the significantly higher Ca:Mg ratios seen in western diets are attributable to firstly the rise in total calories consumed in the United States and secondly the rising content of calcium in foods due to postproduction enrichment [52].

Although several studies have shown that calcium is important for bone health and prevention of osteoporosis [7, 8, 9], not all have reported protective associations [11,53,54]. For example, a meta-analysis of 59 randomized controlled trials reported that increasing dietary calcium intake only slightly increased BMD (0.6%–1.0%) at the femur and the spine (0.7%–1.8%) over 2 y [11]. Another meta-analysis, of 42 observational cohort studies, found no association between dietary calcium intake and risk of fracture and, among individual studies that did show an association between calcium and fracture, associations were weak [54]. Inconsistent findings on the relationship between calcium and bone health may be, in part, due to a lack of consideration of the complex interactions between calcium and other nutrients that are important for bone health, such as magnesium. Most dietary recommendations for bone health have focused on calcium and vitamin D, as vitamin D plays a critical role in bone turnover and calcium absorption through regulation of PTH. Magnesium plays a vital role in the conversion of inactive 25(OH)D into active 1,25(OH) vitamin D through activation of the 1α-hydroxylase enzyme [55]. Specifically, in states of a suboptimal magnesium concentration, 25(OH)D is stored in the tissues rather than activated, decreasing the response of PTH, which, in part, regulates the absorption of calcium [56]. Data from a recent randomized controlled trial suggest that optimizing the magnesium status, through supplementation, may also be important for optimizing the vitamin D status, particularly as 25(OH)D increased [57]. Ionized calcium and magnesium also share a common method of homeostatic regulation through absorption in the gut and reabsorption in the kidneys [57]. It is proposed that these shared mechanisms of absorption and reabsorption are controlled via calcium sensors on cells in blood and in the lumen of the colon [57]. When the sensors detect an elevated concentration of circulating calcium, absorption of both calcium and magnesium is decreased, whereas urinary excretion via the kidneys is increased for both nutrients [58]. These homeostatic mechanisms may explain the nonlinear relationships observed in this study between Ca:Mg and BMD. In states of suboptimal magnesium status, low calcium absorption will also be present due to the reductions in the activation of vitamin D and PTH. Furthermore, in states of elevated calcium intake and average-to-suboptimal magnesium intake, an elevated luminal calcium concentration will shut down channels in the small intestine and kidney responsible for absorption/reabsorption of both nutrients, further supporting the need to balance magnesium and calcium intake. In murine models, alterations in the balance of calcium to magnesium have been shown to impact inflammatory response [59] and oxidative stress [60], both of which are involved in the pathogenesis of bone loss [61,62].

The RDA for calcium is 1000–1200 mg/d for men and women, and for magnesium, it is 300–320 mg/d for women and 400–420 mg/d for men [63,64]. Puerto Rican adults have been shown to have mean calcium and magnesium intakes similar to the RDA or slightly below, depending on sex and age group [34]. To our knowledge, this is 1 of the first studies to examine the relationship between Ca:Mg and bone health outcomes. In this study, individuals in the highest tertile of Ca:Mg had mean intakes that most closely adhered to the RDAs for calcium and magnesium (calcium: 1141 mg/d, magnesium: 319 mg/d), yet they did not show the highest BMD, suggesting that magnesium intake may need to be higher in relation to the RDA for calcium for optimizing bone health. However, these findings could be due to reverse causation in that those who have been told they have low bone mass are more likely to take supplemental calcium. To this point, after excluding those who reported calcium and/or magnesium supplement use, associations between Ca:Mg and osteoporosis were numerically strengthened, although some lost statistical significance, particularly when comparing the highest to the middle Ca:Mg tertile. The smaller sample size among nonsupplement users likely contributed to the loss of statistical significance in some of the groups. Thus, meeting an optimal ratio of Ca:Mg may be more important than meeting the RDA for each nutrient. Our results suggest that a Ca:Mg ratio of 2.2–3.2 is related to the highest hip BMD and lowest prevalence of osteoporosis. In that group, the mean calcium intake was 890 mg/d and that of magnesium was 317 mg/d. Future studies should evaluate: 1) whether this Ca:Mg is optimal for other populations, with differing dietary and lifestyle patterns; and 2) whether meeting this ratio is most beneficial among people meeting the RDA for these nutrients.

Strengths of this study include a large sample size of Puerto Rican adults living on the United States mainland. The study includes comprehensive information on participants’ sociodemographic, lifestyle, and health factors. Limitations include its cross-sectional nature, which leaves it open to possible reverse causation. Furthermore, the cut-offs were made based on the sample distribution and not prior analysis; therefore, it lacks clinical relevance. Future studies are needed to examine the association of changes in Ca:Mg over time in relation to bone loss and osteoporosis.

In conclusion, balanced intakes of both dietary calcium and magnesium are important for maintaining BMD and preventing osteoporosis in a population of older Puerto Rican adults. We found that the middle tertile of Ca:Mg (2.2–3.2) was associated with higher BMD at all 4 anatomical sites and with lower odds of osteoporosis. Our findings may help to improve dietary recommendations around the management and prevention of osteoporosis.

Author contribution

The authors’ responsibilities were as follows—LEF, SEN, and KLT: study design; SEN, KLT, and BDH: study conduct; KLT and BDH: data collection; LEF, SEN, and XZ: data analysis; SEN, KMM, BDH, KLT, and XZ: data interpretation; LEF, SEN, KMM, and KLT: manuscript preparation; SEN, KMM, KLT, BDH, and XZ: approving final version of the manuscript; LEF, SEN, and XZ: took the responsibility for the integrity of the data analysis; and all authors: read and approved the final manuscript.

Data availability

Data described in the manuscript, code book, and analytic code will be made available upon request pending approval of a manuscript proposal found at https://www.uml.edu/Research/UML-CPH/Research/bprhs/.

Funding

This research was funded by the NIH (P01 AG023394, P50 HL105185, and R01 AG027087).

Author disclosures

LEF, KMM, XZ, BDH, KLT, and SEN, no conflicts of interest.

Acknowledgments

We thank our skilled research team for their dedication to this project.

Footnotes

Appendix A

Supplementary data to this article can be found online at https://doi.org/10.1016/j.tjnut.2023.05.009.

Appendix A. Supplementary data

The following is the Supplementary data to this article:

mmc1.docx (26.6KB, docx)

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Associated Data

This section collects any data citations, data availability statements, or supplementary materials included in this article.

Supplementary Materials

mmc1.docx (26.6KB, docx)

Data Availability Statement

Data described in the manuscript, code book, and analytic code will be made available upon request pending approval of a manuscript proposal found at https://www.uml.edu/Research/UML-CPH/Research/bprhs/.

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