Category Archives: Calcium

Review: Dairy for Bones

Abstract

Invited review: Dairy intake and bone health: a viewpoint from the state of the art.

The aim of this review was to focus on the complex relationships between milk and dairy products intake and bone health, with particular emphasis on osteoporosis. The literature was extensively examined to provide an objective overview of the most significant achievements on the subject. Osteoporosis can be defined as a disease characterized by low bone mass and microarchitectural deterioration of bone tissue, leading to enhanced bone fragility and a consequent increase in fracture risk. Although the major determinants of peak bone mass and strength are genetic, major factors during childhood and adolescence may affect the ability to achieve peak bone mass. These include nutrition, particularly calcium and protein intake, physical activity, endocrine status, as well as exposure to a wide variety of risk factors. The role of calcium intake in determining bone mineral mass is well recognized to be the most critical nutritional factor to achieve optimal peak bone mass. The greatest amount of dietary calcium is obtained from milk and dairy foods, which also provide the human diet with vitamin D (particularly for products fortified with vitamin D), potassium, and other macro- and micronutrients. Although studies supporting the beneficial effects of milk or calcium on bone health are predominant in the literature, perplexity or discordance on this subject was expressed by some authors. Discordant data, mainly on the risk of fractures, provided limited proof of the unfavorable effect of dairy intake. More often, discordant works indicate no effect of dairy consumption on bone safety. Some considerations can be drawn from this viewpoint. Milk and dairy products are an optimal source of calcium as well as of other limiting nutrients (e.g., potassium and magnesium), with important effects on bone health. Bioactive components occurring in milk and dairy products may play an essential role on bone metabolism, as shown by in vivo and in vitro studies on colostrum acidic proteins and milk basic proteins. Calcium intake positively affects bone mass and is crucial in childhood and youth for correct bone development. In elderly people, calcium intake as well as vitamin D availability should be carefully checked. As a general conclusion, calcium is essential for bone health, although it will not prevent bone loss due to other factors; in this context, milk and dairy foods are bioavailable, relatively inexpensive sources of calcium for the human diet.

Caroli A, Poli A, Ricotta D, Banfi G…
J. Dairy Sci. Nov 2011
PMID: 22032348 | Free Full Text

This article reviews some of the negative studies on dairy for bones. Including this study. The article concludes with:

In any case, some general conclusions can be drawn. First, milk and dairy products are an optimal source of calcium as well as other limiting nutrients (e.g., potassium and magnesium), with important effects on bone health. Bioactive components occurring in milk and dairy products may play an essential role in bone metabolism, as shown by colostrum acidic proteins and MBP. Calcium intake positively affects bone mass and is crucial in childhood and youth for correct bone development. In elderly people, calcium intake as well as vitamin D availability should be carefully checked. The literature reporting favorable effects of milk and dairy products on bone is highly predominant compared with contradictory papers, including discordant and perplexing works. Discordant data, mainly on the risk of fractures, provided limited proof of the unfavorable effects of dairy intake. The majority of the contradictory papers indicate that dairy consumption does not alter bone safety. The best conclusion comes from Lindsay and Nieves (1994):

“Calcium will not prevent the bone loss due to other factors . . . nonetheless, milk is a bioavailable, relatively inexpensive source of calcium for those who can ingest it.”

Milk Increases Risk of Fracture in Women

Abstract

Milk, dietary calcium, and bone fractures in women: a 12-year prospective study.

This study examined whether higher intakes of milk and other calcium-rich foods during adult years can reduce the risk of osteoporotic fractures.
This was a 12-year prospective study among 77761 women, aged 34 through 59 years in 1980, who had never used calcium supplements. Dietary intake was assessed with a food-frequency questionnaire in 1980, 1984, and 1986. Fractures of the proximal femur (n = 133) and distal radius (n = 1046) from low or moderate trauma were self-reported on biennial questionnaires.
We found no evidence that higher intakes of milk or calcium from food sources reduce fracture incidence. Women who drank two or more glasses of milk per day had relative risks of 1.45 for hip fracture (95% confidence interval [CI] = 0.87, 2.43) and 1.05 for forearm fracture (95% CI = 0.88, 1.25) when compared with women consuming one glass or less per week. Likewise, higher intakes of total dietary calcium or calcium from dairy foods were not associated with decreased risk of hip or forearm fracture.
These data do not support the hypothesis that higher consumption of milk or other food sources of calcium by adult women protects against hip or forearm fractures.

Feskanich D, Willett WC, Stampfer MJ, Colditz GA
Am J Public Health Jun 1997
PMID: 9224182 | Free Full Text

Calcium More or Less Than 800mg Increases Heart Risk, More or Less Than 900mg Increases All-Cause Mortality

Abstract

Dietary calcium intake and mortality risk from cardiovascular disease and all causes: a meta-analysis of prospective cohort studies.

Considerable controversy exists regarding the association between dietary calcium intake and risk of mortality from cardiovascular disease and all causes. Therefore, we performed a meta-analysis of prospective cohort studies to examine the controversy.
We identified relevant studies by searching MEDLINE, Embase, and the Cochrane Library databases between 1 September 2013 and 30 December 2013. Reference lists of relevant articles were also reviewed. Observational prospective studies that reported relative risks and 95% confidence intervals for the association of calcium intake with cardiovascular and all-cause mortality were eligible. Study-specific relative risks were pooled using a random-effects model.
In this meta-analysis, 11 prospective studies with 12 independent cohorts, involving 757,304 participants, were eligible. There was evidence of a non-linear association between dietary calcium intake and risk of mortality from cardiovascular disease (P for non-linearity <0.01) and all causes (P for non-linearity <0.01). A dose-response analysis showed a U-shaped relationship between dietary calcium intake and cardiovascular mortality. Intakes that were lower and higher than around 800 mg/day were gradually associated with a higher risk of cardiovascular mortality. For all-cause mortality, we also observed a threshold effect at intakes around 900 mg/day. The risk of all-cause mortality did not decrease further at intakes above 900 mg/day.
This meta-analysis of prospective cohort studies suggests that dietary calcium intake is associated with cardiovascular mortality in a U-shaped manner and that high dietary calcium intake (>900 mg/day) is not associated with a decreased risk of all-cause mortality.

Wang X, Chen H, Ouyang Y, Liu J…
BMC Med 2014
PMID: 25252963 | Free Full Text

From the full text:

Fig3

Calcium Supplements Associated with Increased Fracture Risk In Women

Abstract

Calcium intake and fracture risk: results from the study of osteoporotic fractures.

The relation between dietary calcium, calcium, and vitamin D supplements and the risk of fractures of the hip (n = 332), ankle (n = 210), proximal humerus (n = 241), wrist (n = 467), and vertebrae (n = 389) was investigated in a cohort study involving 9,704 US white women aged 65 years or older. Baseline assessments took place in 1986-1988 in four US metropolitan areas. Dietary calcium intake was assessed at baseline with a validated food frequency questionnaire. Data on new nonvertebral fractures were collected every 4 months during a mean of 6.6 years of follow-up; identification of new vertebral fractures was based on comparison of baseline and follow-up radiographs of the spine done a mean of 3.7 years apart. Results were adjusted for numerous potential confounders, including weight, physical activity, estrogen use, protein intake, and history of falls, osteoporosis, and fractures. There were no important associations between dietary calcium intake and the risk of any of the fractures studied. Current use of calcium supplements was associated with increased risk of hip (relative risk = 1.5, 95% confidence interval 1.1-2.0) and vertebral (relative risk = 1.4, 95% confidence interval 1.1-1.9) fractures; current use of Tums antacid tablets was associated with increased risk of fractures of the proximal humerus (relative risk = 1.7, 95% confidence interval 1.3-2.4). There was no evidence of a protective effect of vitamin D supplements. Although a true adverse effect of calcium supplements on fracture risk cannot be ruled out, it is more likely that our findings are due to inadequately controlled confounding by indications for use of supplements. In conclusion, this study did not find a substantial beneficial effect of calcium on fracture risk.

Cumming RG, Cummings SR, Nevitt MC, Scott J…
Am. J. Epidemiol. May 1997
PMID: 9149664 | Free Full Text

Calcium Intake of 903mg to 1025mg Associated with Lowest Fracture Risk, More and Less Increases Risk

Abstract

Dietary calcium intake and risk of fracture and osteoporosis: prospective longitudinal cohort study.

To investigate associations between long term dietary intake of calcium and risk of fracture of any type, hip fractures, and osteoporosis.
A longitudinal and prospective cohort study, based on the Swedish Mammography Cohort, including a subcohort, the Swedish Mammography Cohort Clinical.
A population based cohort in Sweden established in 1987.
61,433 women (born between 1914 and 1948) were followed up for 19 years. 5022 of these women participated in the subcohort.
Primary outcome measures were incident fractures of any type and hip fractures, which were identified from registry data. Secondary outcome was osteoporosis diagnosed by dual energy x ray absorptiometry in the subcohort. Diet was assessed by repeated food frequency questionnaires.
During follow-up, 14,738 women (24%) experienced a first fracture of any type and among them 3871 (6%) a first hip fracture. Of the 5022 women in the subcohort, 1012 (20%) were measured as osteoporotic. The risk patterns with dietary calcium were non-linear. The crude rate of a first fracture of any type was 17.2/1000 person years at risk in the lowest quintile of calcium intake, and 14.0/1000 person years at risk in the third quintile, corresponding to a multivariable adjusted hazard ratio of 1.18 (95% confidence interval 1.12 to 1.25). The hazard ratio for a first hip fracture was 1.29 (1.17 to 1.43) and the odds ratio for osteoporosis was 1.47 (1.09 to 2.00). With a low vitamin D intake, the rate of fracture in the first calcium quintile was more pronounced. The highest quintile of calcium intake did not further reduce the risk of fractures of any type, or of osteoporosis, but was associated with a higher rate of hip fracture, hazard ratio 1.19 (1.06 to 1.32).
Gradual increases in dietary calcium intake above the first quintile in our female population were not associated with further reductions in fracture risk or osteoporosis.

Warensjö E, Byberg L, Melhus H, Gedeborg R…
BMJ 2011
PMID: 21610048 | Free Full Text

From the full text:

• Dietary calcium intakes below approximately 700 mg per day in women were associated with an increased risk of hip fracture, any fracture, and of osteoporosis

• The highest reported calcium intake did not further reduce the risk of fractures of any type, or of osteoporosis, but was associated with a higher rate of hip fracture

fig2

Calcium Alone Increases Hip Fractures but Lowers Total Fractures

Abstract

Effect of calcium supplementation on hip fractures.

There have been numerous studies of the effects of calcium supplementation, with or without vitamin D, on fractures. Individually, they have not provided clarity regarding calcium’s anti-fracture efficacy, though they have established that calcium does have beneficial effects on bone density throughout the skeleton in women. Meta-analysis of these data suggests that total fracture numbers are diminished. However, the data from the 5,500 women involved in trials of calcium monotherapy show consistent adverse trends in numbers of hip fractures (relative risk 1.50, 95% CI 1.06-2.12). Observational data from the Study of Osteoporotic Fractures show a similar increase in risk of hip fracture associated with calcium use. We hypothesize that reduced periosteal expansion in women using calcium supplementation might account for the differences in anti-fracture efficacy of calcium at the hip, in comparison with other sites. Until there are further trial results to clarify this area, the present findings suggest that reliance on high calcium intakes to reduce the risk of hip fracture in older women is not appropriate. In addition, those at risk should be looking to other agents with a proven capacity to prevent hip fractures, such as bisphosphonates.

Reid IR, Bolland MJ, Grey A
Osteoporos Int Aug 2008
PMID: 18286218 | Free Full Text

Furthermore, our own recent trial of calcium monotherapy suggested that there might be heterogeneity between the responses of hip and other fractures to calcium supplementation [2], with downward trends in vertebral, forearm, and total osteoporotic fractures, but a significant increase in hip fractures.

[…]

Observational studies have also assessed the relationship between calcium use and fractures. While there is a potential problem of confounding by indication, it is noteworthy that the Study of Osteoporotic Fractures reported an increase in hip fracture risk in postmenopausal women taking calcium supplements of almost identical magnitude to that found in the present meta-analysis (relative risk 1.5; 95%CI, 1.1–2.0) [18]. This consistency across the available intervention studies and a large observational study raises doubts regarding the safety of calcium monotherapy in elderly postmenopausal women, though we cannot completely preclude the possibility that these results are a chance finding arising from the smaller numbers of this particular fracture type.

The adverse effect of calcium monotherapy on hip fractures poses the question of how this could occur when the same intervention has the opposite effect on total fracture numbers.

Review: Calcium Safety and New Recommendations

Abstract

Calcium builds strong bones, and more is better–correct? Well, maybe not.

Calcium supplementation has been considered the gold standard therapy for osteoporosis in the general population. It is given in both the placebo and treatment groups of trials evaluating antifracture efficacy of new therapies. Similarly, calcium-based phosphate binders have been considered the gold standard comparator for all new phosphate binders. However, large randomized trials demonstrate conflicting data on the antifracture efficacy of calcium supplementation, particularly in high doses, in patients with osteoporosis without CKD. In addition, recent data suggest an increased risk for cardiovascular events. These new studies raise safety concerns for the general approach with calcium supplementation and binders. This review describes recent data on the adverse effects of calcium supplementation for osteoporosis and how these new data should affect the strategy for phosphate binder use in CKD.

Jamal SA, Moe SM
Clin J Am Soc Nephrol Nov 2012
PMID: 22837272 | Free Full Text

It is important to note that some clinical practice guidelines have been modified on the basis of this new literature suggesting potential risk. For example, in its recently published evidence-based guidelines, Osteoporosis Canada recommended a total intake of calcium (from diet and supplement) of 1200 mg per day, a decrease from the previous recommendation of 1500 mg in supplements (32). The American Society for Bone and Mineral Research issued a statement regarding the potential risks of calcium supplements and suggested, among other points, that “the beneficial effects of calcium are found with relatively low doses. More is not necessarily better. Individuals should discuss the amount of their calcium intake with their healthcare provider” (33). The Institute of Medicine now recommends a daily dietary reference allowance of calcium of 1000–1200 mg per day in the form of diet and supplements (34,35). Finally, the draft United States Preventive Services Task Force statement, pending public comment (http://www.uspreventiveservicestaskforce.org/draftrec3.htm), currently states “the current evidence is insufficient to assess the balance of the benefits and harms of combined vitamin D and calcium supplementation for the primary prevention of fractures in premenopausal women or in men.” Thus, these authorities acknowledge that although some calcium supplements may be beneficial for bone health, too much calcium may be harmful.

Vitamin K2 (MK-4) + D + Calcium Reduces Lifetime Probability of Fracture by 25%

Abstract

Vitamin K supplementation for the primary prevention of osteoporotic fractures: is it cost-effective and is future research warranted?

Lifetime supplementation with vitamin K, vitamin D(3), and calcium is likely to reduce fractures and increase survival in postmenopausal women. It would be a cost-effective intervention at commonly used thresholds, but high uncertainty around the cost-effectiveness estimates persists. Further research on the effect of vitamin K on fractures is warranted.
Vitamin K might have a role in the primary prevention of fractures, but uncertainties about its effectiveness and cost-effectiveness persist.
We developed a state-transition probabilistic microsimulation model to quantify the cost-effectiveness of various interventions to prevent fractures in 50-year-old postmenopausal women without osteoporosis. We compared no supplementation, vitamin D(3) (800 IU/day) with calcium (1,200 mg/day), and vitamin K(2) (45 mg/day) with vitamin D(3) and calcium (at the same doses). An additional analysis explored replacing vitamin K(2) with vitamin K(1) (5 mg/day).
Adding vitamin K(2) to vitamin D(3) with calcium reduced the lifetime probability of at least one fracture by 25%, increased discounted survival by 0.7 quality-adjusted life-years (QALYs) (95% credible interval (CrI) 0.2; 1.3) and discounted costs by $8,956, yielding an incremental cost-effectiveness ratio (ICER) of $12,268/QALY. At a $50,000/QALY threshold, the probability of cost-effectiveness was 95% and the population expected value of perfect information (EVPI) was $28.9 billion. Adding vitamin K(1) to vitamin D and calcium reduced the lifetime probability of at least one fracture by 20%, increased discounted survival by 0.4 QALYs (95% CrI -1.9; 1.4) and discounted costs by $4,014, yielding an ICER of $9,557/QALY. At a $50,000/QALY threshold, the probability of cost-effectiveness was 80% while the EVPI was $414.9 billion. The efficacy of vitamin K was the most important parameter in sensitivity analyses.
Lifetime supplementation with vitamin K, vitamin D(3), and calcium is likely to reduce fractures and increase survival in postmenopausal women. Given high uncertainty around the cost-effectiveness estimates, further research on the efficacy of vitamin K on fractures is warranted.

Gajic-Veljanoski O, Bayoumi AM, Tomlinson G, Khan K…
Osteoporos Int Nov 2012
PMID: 22398856

Bisphosphonates Showed the Smallest Increase In Fracture Rate Over 10 Years

Abstract

Ten-year fracture risk in the assessment of osteoporosis management efficacy in postmenopausal women: a pilot study.

The aim of the reported longitudinal, retrospective pilot study was to establish changes in 10-year fracture risk in postmenopausal women with respect to applied fracture management.
A group of 191 postmenopausal women with a mean age of 68.76± 6.72 years was divided into subgroups. The subgroups were made up of untreated patients (n = 41), patients treated with vitamin D plus calcium (n = 46), and patients treated with bisphosphonates, vitamin D and calcium (n = 104). Repeated densitometric measurements and clinical data were taken into consideration (both baseline and follow-up). Ten-year fracture risk was established, using FRAX(TM) and Garvan nomograms. The mean follow-up period was 2.01±1.87 years.
Generally, the mean fracture probability increased in the studied women over the observation period. Patients on bisphosphonate therapy demonstrated the smallest increase in fracture probability. The probability rate for either any fractures or hip fractures decreased when the T-score increased. A diminished number of falls non-significantly decreased the probability for hip fractures and any fractures.
Ten-year fracture risk increased irrespective of applied management, while a decreased risk was observed only in women with improved bone status.

Pluskiewicz W, Drozdzowska B, Adamczyk P
Climacteric Feb 2013
PMID: 22335356

Review: Exercise Only Beneficial with Calcium > 1000mg per Day

Abstract

Evidence for an interaction between calcium intake and physical activity on changes in bone mineral density.

Results of trials on the effects of physical activity on bone mineral density (BMD) are conflicting. The current hypothesis was that calcium intake modifies the bone response to physical activity. Published trials on physical activity and bone density were reviewed, and the results of 17 trials are summarized. Physical activity has beneficial effects on BMD at high calcium intakes, with no effect at mean calcium intakes less than a mean of 1000 mg/day. The modifying effect of calcium intake on BMD among exercise groups is more pronounced in the lumbar spine than in the radius. This analysis may explain conflicting results of trials on physical activity and calcium effects on bone. Controlled trials designed to test adequately this hypothesis are needed.

Specker BL
J. Bone Miner. Res. Oct 1996
PMID: 8889855