ORIGINAL ARTICLE
Calcium intake, bone mineral density, and fragility fractures:
evidence from an Italian outpatient population
Letizia Vannucci1&Laura Masi2&Giorgio Gronchi3&Caterina Fossi1&
Anna Maria Carossino1&Maria Luisa Brandi1
Received: 3 November 2016 / Accepted: 30 March 2017
# International Osteoporosis Foundation and National Osteoporosis Foundation 2017
Abstract
Summary This study was performed in 1000 adult Italian sub-jects to focus on the effects of dietary calcium intake on bone health. A higher fracture risk appears to be associated with a reduced calcium intake. An adequate daily calcium intake is recommended to counteract osteoporotic fractures.
Purpose The principal aim of the present study was to focus on the effects of dietary calcium intake on bone mineral den-sity (BMD) and fragility fractures in a representative sample of an adult Italian outpatient population.
Methods The study group consisted of 1000 consecutive adult Italian subjects [838 women (F) and 162 men (M)] referred to the Bone Metabolic Diseases Unit for the evaluation of their bone metabolism. Daily dietary calcium intake was assessed using a specific food frequency questionnaire (FFQ). Other evaluations included fracture risk, lumbar and femoral BMD, heel ultrasound, fragility fractures, plasma concentra-tion of parathyroid hormone ([PTH]) and 25-hydroxy-vitamin D ([25(OH)D]), and urinary calcium.
Results Only 10.4% of the subjects (n = 104; 71 F and 33 M) had a daily calcium intake adequate for adults (≥1000 mg/ day). No correlation was found between calcium intake and BMD. The transition from a daily dietary calcium intake
<400 mg/day to a daily dietary calcium intake≥400 mg/day was associated with a reduced fracture probability ratio at any site [from 42 to 21% (p < 0.05)]. Subjects with one or more vertebral fractures had a significantly lower dietary calcium intake (<400 mg/day) than did subjects without vertebral frac-tures, and they practiced physical activity only occasionally (p = 0.030).
Conclusions Daily dietary calcium intake is lower than the recommended daily intake in an Italian ambulatory popula-tion, and a higher fracture risk appears to be associated with a reduced calcium intake. An age-adequate daily calcium in-take, combined with regular physical activity, is strongly rec-ommended in order to counteract fragility fractures.
Keywords Calcium intake . Bone mineral density . Fragility fractures . Physical activity
Introduction
The inadequacy of dietary calcium intake is a global problem The daily requirement of calcium varies with age from a min-imum of 700 mg/day during the first years of life to 1000– 1200 mg/day in adults [1,2]. Particularly, in the adult popu-lation, the recommended dietary allowance (RDA) of calcium is 1000–1200 mg/day, but a daily calcium intake of 1400 mg should be considered necessary for postmenopausal women. Nevertheless, 800 mg/day of calcium intake is considered the minimal requirement in adults, as it is the limit below which bone loss is accelerated and calcium balance becomes nega-tive [2]. The estimated average requirement (EAR) of a nutri-ent indicates its average minimal requiremnutri-ent [3]; EAR is usually 200 mg lower than RDA [2]. The main sources of dietary calcium are dairy products, which supply up to 2/3 of the population’s calcium intake in Western countries [4],
* Maria Luisa Brandi marialuisa.brandi@unifi.it
1
Bone Metabolic Diseases Unit, Department of Surgery and Translational Medicine, University of Florence, Viale Pieraccini 6, 50139 Florence, Italy
2
Bone Metabolic Diseases Unit, University Hospital AOU-Careggi, Largo Palagi 1, 50139 Florence, Italy
3 Department of Neurosciences, Psychology, Drug Research, and
Child Health (section of Psychology), University of Florence, Via di San Salvi 12, 50139 Florence, Italy
and represent a source of easily absorbable calcium [5] and essential nutrients including proteins and phosphorus [6]. Some vegetables and fruits contain considerable amounts of calcium [5], even if their contribution can be sometimes lim-ited because of the small average serving size of these foods; calcium-rich water can also be useful as a supplement [5]. Calcium-rich foods are generally recommended, rather than calcium supplements [7], whose use should be limited to sub-jects who do not consume sufficient calcium through their diets and are at high risk for osteoporosis or fractures [4]. In fact, calcium supplements can cause gastrointestinal side ef-fects, and they can increase the risk of kidney stones [8]; according to a part of the literature, they may also increase cardiovascular risk, especially among postmenopausal wom-en over 80 years of age [9]. However, data from a recent meta-analysis showed the cardiovascular safety of calcium supple-ments [10].
The association between calcium intake and bone mineral density (BMD) is not straightforward [11]. The regular intake of milk during childhood positively influences bone density in adults [6,12]; however, in pre- and post-menopausal women and in elderly men, calcium appears to show a threshold ef-fect; thus, a very low calcium intake correlates with a very low BMD, while an intake above the recommended amounts does not produce additional benefits [2,5].
The effect of an adequate calcium intake on the incidence of fractures remains uncertain [4,5]. Although some studies have shown that low calcium intake is associated with an increased risk of fragility fractures from the age of 80 years [13]—of hip fractures, particularly [2]—the effect of a normal or high calcium intake on fracture rate is inconsistent [11,14]. The principal aim of the present study was to evaluate the dietary calcium intake in a representative sample of an adult Italian outpatient population. A further aim of the study was to evaluate the correlations between dietary calcium intake and bone metabolic markers, densitometric parameters (BMD, heel ultrasound bone density), and on fragility fractures in a representative sample of an adult Italian outpatient population.
Subjects and methods
Study population
The study group consisted of 1000 consecutive adult Caucasian subjects [838 Italian women (F) and 162 Italian men (M)] re-ferred to the Bone Metabolic Diseases Unit for the evaluation of their bone metabolism.
The study population has been characterized by interviewing each subject regarding changeable and not-changeable fracture risk factors [11,15]. Besides age and gender, anthropometric parameters such as height, weight, and ethnicity were evaluated. Family history of fragility fractures at any skeletal site and
lifestyle features such as current smoking and consumption of alcohol (arbitrarily defined as at least one glass of wine per day), type of occupation, and physical activity (at least 2 h per week) were also investigated. Finally, current or previous chronic cor-ticosteroid (CCS) therapy and/or hormone replacement therapy (HRT) were considered. The study was approved by the local ethics committee of Careggi Hospital, and informed consent was obtained from all individual participants included in the study. Assessment of calcium intake
Daily dietary calcium intake was assessed for each subject using a specific food frequency questionnaire (FFQ) validated for Italian people [16], which was administered at the time of the densitometric measurement. A calculation procedure was per-formed to calculate daily dietary calcium intake from each FFQ. Subjects who took calcium supplements at the time of the study enrolment were excluded from the study.
Densitometric measurement and assessment of fracture Total lumbar spine and femoral neck BMD (g/cm2) was obtained using a dual-energy X-ray absorptiometry (DXA-Hologic Delphi). Heel bone density was also evaluated using a quantita-tive ultrasound (QUS-GE Achilles InSight) consisting of two ultrasound measurement techniques, velocity of sound (VOS) and broadband ultrasound attenuation (BUA).
Personal history of fragility fractures at typical skeletal sites (vertebrae, hip, and wrist) and at any other skeletal site was reported by interview and/or review of medical records and/or hospitalization review. Non-traumatic fractures or low trauma-associated fractures were considered as fragility fractures.
Laboratory parameters
Plasma concentration of parathyroid hormone ([PTH]) and 25-hydroxy-vitamin D ([25(OH)D]) and urinary calcium were evaluated for each subject. The following normal ranges were considered: [PTH] 10–65 pg/mL; urinary calcium 100– 300 mg/24 h. A value of [25(OH)D]≥30 ng/mL was consid-ered adequate [17].
Statistical analysis
Continuous data were expressed as mean ± standard deviation (SD) and as median (range). Categorical data were expressed as numbers (and percentages). The comparison of medians was performed using the Kruskal-Wallis test. A generalized linear model was used to determine a statistically significant difference between daily dietary calcium intake (<400 mg/day versus≥400 mg/day) on fragility fractures taking into account gender as a fixed effect and age as a covariate.
The association between physical activity and fractures was evaluated by a one-tail Fisher’s exact test and Mann-Whitney U test. Cases were excluded from statistical analysis for the dependents for which they had missing data. All the analyses were carried out with SPSS statistical package. The level of statistical significance was considered as p < 0.05.
Results
Complete data of the entire study population, according to gender, are summarized in Table1. The age of the study group ranged from 19 to 89 years for females and from 20 to 78 years for males.
According to the femoral neck Z-score values (standard deviations from normal-for-age BMD values), 289 subjects (243 F and 46 M) were osteoporotic, whereas 426 subjects (355 F and 71 M) were osteopenic; 285 subjects (240 F and 45 M) had normal femoral neck Z-score values.
Dietary calcium intake
In our study group, daily calcium intake derived from foods ranged from a minimum of 106 mg/day to a maximum of
1250 mg/day, with a mean value of 620.7 ± 256.5 mg/day. As RDA for calcium is set at 1000–1200 mg/day in adults [1,2], a daily intake of 1000 mg can be considered adequate in the adult population. Therefore, the mean value of daily calcium intake of our study group was well below the level of recommended daily intake, as well as below the level of EAR, which is usually set 200 mg lower than RDA [2]. As shown in Fig.1, only 10.4% of the subjects (n = 104; 71 F and 33 M) had a daily dietary calcium intake adequate for adults (≥1000 mg/day), whereas the remaining 89.6% (n = 896; 767 F and 129 M) had a daily calcium intake not adequate for adults (<1000 mg/day) [1,2]. Particularly, 3.4% (n = 34; 28 F and 6 M) had a daily calcium intake between 800 and 999 mg, thus not achieving RDA, but at least achieving the average minimal required calcium intake which is considered to be 800 mg/day [1,2]; 86.2% (n = 862; 739 F and 123 M) had a daily calcium intake <800 mg (Fig.1). Of the subjects, 10.5% (n = 105; 75 F and 30 M) had a markedly low daily dietary calcium intake (<400 mg/day).
Calcium intake, lifestyle, and fragility fractures
There was a significant effect of daily dietary calcium intake (<400 versus ≥400 mg/day) on fragility fractures
Table 1 Main features of the
study group (n = 1000) FEMALES (n = 838) MALES (n = 162)
White race, n (%) 838 (100) 162 (100) Age (years) 62.0 ± 14.0 53.7 ± 13.1 Weight (kg) 61.2 ± 14.6 80.7 ± 10.1 Height (cm) 159.6 ± 9.6 174.5 ± 6.3 Daily dietary calcium intake (mg/day) 620.7 ± 253.4 621.5 ± 268.5 Lumbar BMD (g/cm2) 0.9 ± 0.1 1.0 ± 0.2
Femoral neck BMD (g/cm2) 0.7 ± 0.1 0.8 ± 0.1
BUA 60.2 ± 8.4 58.8 ± 6.6
VOS 1496.1 ± 65.9 1479.8 ± 78.0 Subjects with at least one fragility fracture at
any skeletal site, n (%)
116 (13.8) 84 (51.8) Subjects with vertebral fracture/s, n (%) 68 (8.1) 5 (3) Subjects with hip fracture, n (%) 29 (3.4) 3 (1.8) Subjects with wrist fracture, n (%) 28 (3.3) 7 (4.3) [25(OH)D] (ng/mL) 25.1 ± 8.0 33.6 ± 10.9 [PTH] (pg/mL) 51.2 ± 24.9 40.2 ± 23.6 Urinary calcium (mg/24 h) 121.5 ± 60.9 150.5 ± 61. Parental fracture history, n (%) 68 (8.1) 13 (8.0) Alcohol, n (%) 110 (13.1) 21 (12.9) Current smoking, n (%) 46 (5.4) 8 (4.9) Active occupation, n (%) 30 (3.5) 5 (3.0) Outdoor occupation, n (%) 43 (5.1) 6 (3.7) Physical activity for at least 2 h per
week, n (%)
98 (11.6) 116 (71.6) CCS for at least 3 months, n (%) 9 (1.0) 4 (2.4)
HRT n (%) 118 (14.0) 0 (0)
Continuous data were expressed as mean ± standard deviation (SD). Categorical data were expressed as numbers (and percentages)
kg kilograms, cm centimeters, mg milligrams, g grams, ng nanograms, pg picograms, h hours, BMD bone mineral density, BUA broadband ultrasound attenuation, VOS velocity of sound, 25(OH)D 25-hydroxy-vitaminD, PTH parathyroid hormone, CCS corticosteroid therapy, HRT hormone replacement therapy
(F(1952)= 5.51, p < 0.05). Indeed, the group of subjects with a very low calcium intake (<400 mg/day) had an observed frac-ture probability ratio of 42%, and it fell to 21% in the group with a daily calcium intake≥400 mg/day. Therefore, a daily dietary calcium intake > or equal to 400 mg reduced the fracture probability ratio at any site by 50% (Fig.2). There was also a significant effect of the gender (F(1952)= 83.17, p < 0.001). The assumption of the independence between the covariate and the fixed effect (calcium intake) was fulfilled (p = n.s.). The covariate, age, was significantly related to fragility fractures (F(1952) = 32.85, p < 0.001); the adjusted model was evaluated at a value of age of 59.87. All interaction effects were statistically non-significant.
A statistically significant relation was found between the pres-ence of vertebral fractures and physical exercise only in the sub-sample of women older than 70 years. Indeed, a statistically significant difference was found between the number of subjects with one or more vertebral fractures (n = 0) in the group of subjects who practiced physical exercise for at least 2 h per week (n = 11) and the number of subjects with vertebral fractures
(n = 44) in the group who practiced physical activity only occa-sionally (n = 156). Particularly, 28% of subjects who practiced occasional physical activity had vertebral fractures, which were not present in the subjects who practiced physical exercise at least 2 h per week (p = 0.031) (Table2). Thus, in old women, vertebral fractures were significantly less frequent in subjects who practiced physical exercise compared to subjects who exercised only occasionally. Conversely, no association was ob-served between physical activity and presence of fractures at any other site.
Moreover, with regard to the whole sample, when introducing daily dietary calcium intake as an adjunctive parameter in the comparative analysis of subjects with and without vertebral frac-tures, a significant difference in the level of daily calcium intake as well as in the attitude toward physical activity could be ob-served between the two groups. Subjects with one or more ver-tebral fractures had a significantly lower daily dietary calcium intake (<400 mg/day) than did subjects without vertebral frac-tures, and they practiced physical activity only occasionally, whereas subjects without vertebral fractures had a daily dietary ≥1000 mg/day 800-999 mg/day <800 mg/day 86.2% 10.4% 3.4% Fig. 1 Daily dietary calcium
intake (mg/day) in the whole study population
42%
p<0.05
Daily dietary calcium intake (mg/day)
Fracture probability
ratio
21%
Fig. 2 Association between daily dietary calcium intake and fragility fractures
calcium intake≥400 mg/day and practiced regular physical ex-ercise for at least 2 h per week (U = 27389; p = 0.030) (data not shown).
Calcium intake and densitometric and laboratory parameters
No correlation was observed between daily dietary calcium intake and bone densitometric parameters. We found no sig-nificant difference in the median values of total lumbar BMD, femoral neck BMD, BUA, and VOS between groups with different daily calcium intake, whatever value of calcium in-take was considered as a threshold (data not shown).
Similarly, whatever threshold of calcium intake was con-sidered, no significant difference was observed in the median values of [PTH], [25(OH)D], and urinary calcium between groups with different daily dietary calcium intake (data not shown).
Discussion
Our study indicates that daily dietary calcium intake was in-sufficient in our representative sample of an adult Italian out-patient population, with average values, shown in Table 1, much lower than both RDA for the adult population (1000– 1200 mg/day) [1,2] and the average minimal requirement, which is usually set at 800 mg/day for adults [2]. Almost the whole study population (89.6%) had a daily dietary calcium intake below 1000 mg/day, and only a minority of subjects presented a calcium intake adequate for adults, considering RDA values for this element [1,2]. Even when considering the minimal requirement to define a level of sufficiency of daily calcium intake [2], only a minority of subjects showed a sufficient dietary calcium intake, as most of the study pop-ulation (86.2%) had a daily calcium intake below 800 mg, indeed.
In accordance with other limited published data [2,18], our study shows a significant association between calcium intake and fragility fractures. Subjects who consumed a small
amount of calcium from foods (<400 mg/day) had an age-and gender-adjusted higher fracture probability ratio than those with a daily dietary calcium intake ≥400 mg/day; in particular, a calcium intake≥400 mg/day halved the fracture probability ratio from 42 to 21% (p < 0.05), although 400 mg could not be considered a sufficient level of daily calcium intake for adults [1,2].
Moreover, in agreement with a part of the literature [19, 20], our study also demonstrates that the combination of die-tary calcium intake and physical activity significantly influ-enced bone health. The presence of one or more vertebral fractures was significantly associated with a very low dietary calcium intake and physical inactivity, whereas a daily dietary calcium intake of 400 mg/day or more and regular physical activity of at least 2 h per week were significantly associated with the absence of vertebral fractures (p = 0.030).
The important role of physical activity in women older than 70 years arose from our study. Age-adequate regular physical exercise was significantly associated with lower prevalence of vertebral fractures in older women. Although the result did not have a clear unique interpretation, it could be speculated that women with a positive attitude toward physical exercise throughout life were protected from fragility vertebral frac-tures, thus suggesting a hypothetical protective role of physi-cal activity.
It is well known that 400 mg/day does not represent a limit of sufficiency for daily calcium intake in adults [1,2]; how-ever, in our study, this value appeared to be the threshold below which the calcium content was so deficient that the physiological functions that calcium usually exerts in the skel-eton could not be ensured. Thus, a calcium intake of 400 mg/ day or more appeared to allow a partial restoration of such functions, with consequent decline of fracture probability ratio from 42 to 21%. It could be hypothesized that in presence of daily calcium intake dramatically lower than both RDA and the minimal requirement, such as 400 mg/day [1,2], even minimal increases of calcium intake could be able to deter-mine significant physiological effects on bone health.
We then investigated the link between daily dietary calcium intake and fragility fractures; in particular, we investigated which physiological functions may be recovered by a daily calcium intake≥400 mg/day.
As no correlation between daily calcium intake and lumbar and femoral neck BMD was found in our study, nor between calcium intake and heel bone density measured by QUS, it could be speculated that calcium intake affected fragility frac-tures independently of BMD.
According to a part of the literature which shows the com-plexity and the non-linearity of the relationship between cal-cium intake and bone density [5,14,21], and despite the well-known effects of calcium on bone health, which are supposed to be mediated by an increase in BMD [18,22], and despite the bone loss that is associated with inadequate calcium intake
Table 2 Association between physical activity and vertebral fractures in women older than 70 years
Physical activity for at least 2 h per week (n = 11) Only occasional physical activity (n = 156) Subjects without vertebral fractures, n (%) 11 (100) 112 (71.8) Subjects with vertebral fracture/s, n (%) 0 (0) 44 (28.2) p = 0.031
through the mobilization of calcium from bone [23], our study shows that current calcium intake did not affect BMD in the study population.
BMD is a complex parameter, with wide variation among individuals, which depends on genetic factors [1], body weight and composition [24], physical exercise and lifestyle [25], and hormonal status [26]. Such factors play a significant role in adults [23], but they are crucial during childhood and adolescence for the achievement of an adequate peak bone mass [1]. Thus, the influence of factors other than calcium on BMD could partly explain the lack of correlation between current calcium intake and BMD at any skeletal site arising from our study. Moreover, it may be speculated that correla-tion between BMD and calcium intake could become evident in a larger study group and in presence of simpler statistical outcomes.
It should also be remembered that our study evaluated cur-rent calcium intake in an adult population without considering the subjects’ dietary calcium intake earlier in their lives. As dietary calcium intake during childhood positively influences BMD values in adults [12], such a factor could have contrib-uted to the discrepancy between current calcium intake and BMD observed in our study. Given the physiological correla-tion between absorbed and excreted calcium, and since PTH is considered to be an indicator of calcium nutritional status [23], the lack of correlation between daily calcium intake and uri-nary calcium, [PTH] and [25(OH)D] observed in our study could be justified by abnormalities of intestinal absorption of calcium in some of the enrolled subjects.
Moreover, circulating levels of [25(OH)D], influenced by the season during which they were measured [1], which did not reach values of sufficiency in the female subjects of the study group, could have negatively affected intestinal absorp-tion of calcium.
The consequent discrepancy between ingested and absorbed calcium, not evaluated in the present study, could partly explain the failure of the association between calcium intake and BMD.
Therefore, it could be speculated that the association be-tween calcium intake and fragility fractures observed in our study was mediated by bone qualitative aspects rather than bone quantitative features. In fact, fragility fracture risk de-pends not only on loss of BMD but also on alterations of bone quality [27–29] and calcium, 99% of which is included in the skeleton, predominantly affects bone mineralization [2]. A very low daily dietary calcium intake (<400 mg/day) probably leads to a depletion in body calcium content which could compromise good bone mineralization, thus increasing frac-ture risk.
Our study has some limitations. It is a cross-sectional study, not a randomized controlled trial, so its level of evidence is weaker. Moreover, when observing features of the study pop-ulation, summarized in Table1, it could be noted that men
were younger than women but surprisingly, they had a higher prevalence of fragility fractures. These specific differences between sex, which could be attributed to the greater self-healthcare of women, highlight the fact that men enrolled in our study might be considered as a partially representative sample of the male general population.
The strength of our study is that, to our knowledge, it is the first one reporting a descriptive analysis of daily dietary cal-cium intake in the adult Italian population.
In conclusion, our study shows that daily dietary calcium intake is lower than the recommended level in a representative sample of an adult Italian outpatient population.
The study highlights the importance of an adequate dietary calcium intake that is in accordance with calcium RDA for adults (1000–1200 mg/day), as low calcium intake (<400 mg/ day) increases fracture probability and is significantly associ-ated with vertebral fractures. It also suggests a protective role of physical exercise on fragility vertebral fractures, which ap-pears to be particularly important in older women. An age-adequate daily calcium intake, combined with regular physical activity, is strongly recommended in order to counteract fra-gility fractures, especially at the spinal site.
Acknowledgements This study was supported by an unrestricted grant from F.I.R.M.O. (Fondazione Raffaella Becagli) to M. L. Brandi.
Compliance with ethical standards
Ethical approval All procedures performed in studies involving hu-man participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.
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