Calcium intake and risk of fracture: systematic reviewBMJ 2015; 351 doi: https://doi.org/10.1136/bmj.h4580 (Published 29 September 2015) Cite this as: BMJ 2015;351:h4580
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Despite not reducing osteoporotic fractures, Calcium supplements can increase patient risks for myocardial infarction and ischemic stroke.
Competing interests: No competing interests
Bahat and colleagues argue that the findings of our systematic review on calcium intake and fracture1 do not apply to frail older adults. No randomized controlled trial of calcium supplements with frailty as an entry criterion has been conducted. Therefore, it is incorrect to suggest that calcium supplements prevent fractures in people with frailty or that our analyses are invalid. Only one trial with fracture as the primary endpoint has been performed in people in residential care.2,3 As we discussed in our paper, the specific features of the trial population mean the results are not broadly generalizable. It should not be assumed that frail elderly people will obtain the same benefits from calcium and vitamin D as occurred in that study. In the RECORD study,4 all participants (mean age 77y) had a previous low-trauma osteoporotic fracture and about 17% died during study follow-up of 42 months indicating frailty was likely to have been common in participants. Calcium with or without vitamin D had no effect on fractures in the entire study cohort, nor in subgroups likely to have the highest level of frailty (age >80y, previous hip fracture, and body weight < 55kg).4
Bahat and colleagues unwisely dismiss concerns about side-effects of calcium supplements in frail people. Adverse events are likely to have greater impact in people with limited resilience. In a 1y trial in elderly people living in residential care, the addition of calcium supplements to sunlight exposure increased all-cause and cardiovascular mortality.5,6 Likewise, in our patient-level meta-analysis of calcium supplements, an increased risk of myocardial infarction was apparent by 1y.7 Thus, cardiovascular and other side-effects of calcium supplements are just as relevant to the frail elderly as they are to other patient groups. Bahat and colleagues state that we only commented on the cardiovascular side-effects of calcium supplements in our article. Unfortunately, they appear to have overlooked the paragraph in the Discussion that discusses other side-effects of calcium which include gastrointestinal side-effects, kidney stones, as well as increased risk of cardiovascular events.1
We are disappointed that Bahat and colleagues misrepresented our response to the Reviewers “In their author response…” They selectively highlighted one sentence while ignoring the following text, which specifically addressed the issue of observational studies on the topic and the results of the Women’s Health Initiative they cite. As stated in our response letter, we remain unaware of any paper that refutes the findings from our previous systematic reviews that calcium supplements with or without vitamin D increase the risk of myocardial infarction in randomised, placebo-controlled trials.
We agree with Bahat and colleagues that a major focus for osteoporosis management is the frail elderly, but current evidence does not support a role for calcium supplements in this population group. Drawing this conclusion is not akin to “disregarding fragile older adults”. Instead, it helps to avoid the prescription of ineffective therapies, allowing focus on treatments with efficacy. Further research would be welcome and we suggested potential topics related to calcium supplements in our recent papers.1,8
1. Bolland MJ, Leung W, Tai V, Bastin S, Gamble GD, Grey A, et al. Calcium intake and risk of fracture: systematic review. BMJ 2015;351:h4580.
2. Chapuy MC, Arlot ME, Duboeuf F, Brun J, Crouzet B, Arnaud S, et al. Vitamin D3 and calcium to prevent hip fractures in the elderly women. N Engl J Med 1992;327:1637-42.
3. Chapuy MC, Arlot ME, Delmas PD, Meunier PJ. Effect of calcium and cholecalciferol treatment for three years on hip fractures in elderly women. BMJ 1994;308:1081-2.
4. Grant AM, Avenell A, Campbell MK, McDonald AM, MacLennan GS, McPherson GC, et al. Oral vitamin D3 and calcium for secondary prevention of low-trauma fractures in elderly people (Randomised Evaluation of Calcium Or vitamin D, RECORD): a randomised placebo-controlled trial. Lancet 2005;365:1621-8.
5. Sambrook PN, Cameron ID, Chen JS, Cumming RG, Durvasula S, Herrmann M, et al. Does increased sunlight exposure work as a strategy to improve vitamin D status in the elderly: a cluster randomised controlled trial. Osteoporos Int 2012;23:615-24.
6. Reid IR, Bolland MJ, Sambrook PN, Grey A. Calcium supplementation: Balancing the cardiovascular risks. Maturitas 2011;69:289-95.
7. Bolland MJ, Avenell A, Baron JA, Grey A, Maclennan GS, Gamble GD, et al. Effect of calcium supplements on risk of myocardial infarction and cardiovascular events: meta-analysis. BMJ 2010;341:c3691.
8. Tai V, Leung W, Grey A, Reid IR, Bolland MJ. Calcium intake and bone mineral density: systematic review and meta-analysis. BMJ 2015;351:h4183.
Competing interests: No competing interests
Conclusions not recommending increasing calcium intake for fracture prevention should be handled cautiously: They are not valid for the fragile older population
We read the study and their accompanying letter on the calcium intake and risk of fracture1,2 by Bolland et al., with great interest, in which they performed systematic review of randomized controlled trials and observational studies of calcium intake with fracture as an endpoint.
In this study, the authors analyzed calcium supplementation trials in the general population including mostly healthy participants. They also noted that the trials were generally carried out in healthy populations or those at risk of osteoporosis. They did not include the “specific” joint analysis of the studies performed only in fragile older adults in the study design nor in their corresponding discussion. This causes their some lack of data in the real osteoporotic fragile older population expected to have hazardous consequences of osteoporosis. The osteoporotic fracture risk is especially prevalent with very significant consequences in this sub-population. Of course, the probability of a fracture - hence the effect of a given treatment modality to the rate of fractures - would be higher and more significant in this older sub-population. The data suggesting calcium and vitamin D administered to people living in residential care but not in the community prevents fractures, is very notable in this context.3
Furthermore, they stated as a “major” conclusion that calcium supplements have small inconsistent benefits on fracture reduction but probably have an unfavourable risk: benefit profile. This is also questionable as fragile adults would have limited life expectancy, limiting the possibility of unfavourable outcomes related to such complications but be affected by osteoporotic fractures. As another “major” conclusion they stated that their results suggest that clinicians, advocacy organisations, and health policymakers should not recommend increasing calcium intake for fracture prevention, either with calcium supplements or through dietary sources. They repeated this in their letter to their own article. We suggest that this very assertive conclusion - disregarding fragile older adults - may have very hazardous consequences. The related media reports may prevent older fragile people receiving calcium which could be a malpractice affecting that significant population.
On the other hand, they reported in the decision letter that in their analysis, the results for calcium monotherapy did not differ substantially from those for calcium with vitamin D, except at the hip, which is due to the influence of the Chapuy trials4, as discussed in detail in the text. However, hip fractures are the major fractures resulting in disability which affect the – currently incompletely analysed - fragile older population. The authors suggested that based on the average low vitamin D concentrations in the Chapuy study, it is possible that many participants had unrecognised osteomalacia, the treatment of which might have led to the benefits observed. They concluded that – therefore - the benefits of calcium and vitamin D in this study should not be expected to be reproduced in cohorts with higher vitamin D concentrations. However, as the authors also noted in the study, the influence of Chapuy trail5 is the feature of previous meta-analysis that concluded that co-administered calcium and vitamin D but not vitamin D prevents fractures6 signifying the beneficial effect of calcium alone. Furthermore, post-fracture prescribed calcium and vitamin D supplements is reported to be associated with lower mortality in elderly hip fracture patients in a prospective analysis.7
Another point is that as the authors mentioned many of the RCTs were of short duration - which are therefore inadequate to suggest that their insignificant result for beneficial fracture risk reduction in longer follow-ups. This is an important issue in real-life and is not included in their “major” conclusions.
Additionally, the authors only commented on the risks associated with calcium supplements and CVD in the article. In their author response document4, the authors stated that they are not aware of any publication that refutes that calcium supplements with or without vitamin D increase the risk of myocardial infarction. However, there are significant publications that refute this hypothesis.8-10
In conclusion, we suggest that the reports commenting on osteoporotic fractures – including this one - should include a major emphasis on fragile older adults in their conclusions since they are the most significant population suffering from fracture consequences.
1. Bolland MJ, Leung W, Tai V, Bastin S, Gamble GD, Grey A, Reid IR. Calcium intake and risk of fracture: systematic review. BMJ 2015;351:h4580.
3. Avenell A, Gillespie WJ, Gillespie LD, O’Connell D. Vitamin D and vitamin D analogues for preventing fractures associated with involutional and post-menopausal osteoporosis. Cochrane Database Syst Rev 2009:2;CD000227.
5. Chapuy MC, Arlot ME, Duboeuf F, et al. Vitamin D3 and calcium to prevent hip fractures in the elderly women. N Engl J Med 1992;327:1637-42.
6. Boonen S, Lips P, Bouillon R, Bischoff-Ferrari HA, Vanderschueren D, Haentjens P. Need for additional calcium to reduce the risk of hip fracture with vitamin D supplementation: evidence from a comparative metaanalysis of randomized controlled trials. J Clin Endocrinol Metab 2007;92:1415-23.
7. Nurmi-Lüthje I, Lüthje P, Kaukonen JP, Kataja M, Kuurne S, Naboulsi H, Karjalainen K. Post-fracture prescribed calcium and vitamin D supplements alone or, in females, with concomitant anti-osteoporotic drugs is associated with lower mortality in elderly hip fracture patients: a prospective analysis. Drugs Aging 2009;26:409-21.
8. Shah SM, Carey IM, Harris T, DeWilde S, Cook DG. Calcium supplementation, cardiovascular disease and mortality in older women. Pharmacoepidemiol Drug Saf 2010;19:59-64.
9. Bhattacharya RK. Does widespread calcium supplementation pose cardiovascular risk? No: concerns are unwarranted. Am Fam Physician 2013;87(3):Online.
10. Hsia J, Heiss G, Ren H, et al. Women's Health Initiative Investigators. Calcium/vitamin D supplementation and cardiovascular events. Circulation 2007;115:846-54.
Competing interests: No competing interests
Several major osteoporosis advocacy groups have responded in statements on their websites to our systematic reviews of calcium intake on bone density and fracture.1,2 Their responses largely contradict the research findings and continue to recommend high calcium intake for bone health, despite the evidence that this is ineffective. All the groups have scientific committees but despite some making criticisms of our work in their website statements, none has formally responded to our publications with a letter to the editor.
One statement claims that media reports about the research are wrong and should be ignored, and implies that the research findings are incorrect.3 Two statements claim that achieving the recommended intake of calcium is necessary for optimum bone health, and that low calcium intake causes poor bone health or osteoporosis.3,4 Three statements recommend at least 1000 mg/day of calcium.4-6 Four statements recommend dietary intake as the primary source of calcium and the use of calcium supplements if the recommended levels cannot be achieved.3-6 One statement recommended high calcium intake only for those people taking osteoporosis medications.7 Despite the large number of trials and cohort studies already conducted, one statement called for more studies.5 None of these recommendations are supported by the findings of our systematic reviews.
All of the osteoporosis advocacy groups’ websites emphasize the importance of calcium for bone health. None of the websites or recent statements about calcium intake suggests that increasing dietary calcium intake or taking calcium supplements might have very small, if any, effects on bone density or fractures. Only the UK National Osteoporosis Society suggests that the majority of people have an adequate calcium intake from a standard diet.8
We are concerned that major osteoporosis advocacy groups continue to make recommendations about calcium intake and bone health in older people that are not supported by available evidence. Previously, we noted that advocacy groups and professional societies that most strongly advocate for increasing calcium intake receive financial support from companies with vested interests, and fail to declare this information in their statements and correspondence.9 Given their purported focus on improving care for patients with or at risk of osteoporosis, we think that osteoporosis advocacy organisations should provide accurate, evidence-based recommendations about the lack of efficacy of increasing calcium intake in osteoporosis prevention and management.
1. Tai V, Leung W, Grey A, Reid IR, Bolland MJ. Calcium intake and bone mineral density: systematic review and meta-analysis. BMJ 2015;351:h4183.
2. Bolland MJ, Leung W, Tai V, Bastin S, Gamble GD, Grey A, et al. Calcium intake and risk of fracture: systematic review. BMJ 2015;351:h4580.
3. http://www.iofbonehealth.org/news/scientific-evidence-supports-role-calc... (accessed16.11.2015)
4. http://nof.org/files/nof/public/content/file/5814/upload/1252.pdf (accessed16.11.2015)
5. http://www.osteoporosis.ca/how-does-calcium-affect-bone-health-and-fract... (accessed16.11.2015)
6. http://www.osteoporosis.org.au/osteoporosis-australias-statement-regardi... (accessed16.11.2015)
7. https://www.nos.org.uk/about-us/news (accessed16.11.2015)
8. https://www.nos.org.uk/healthy-bones-and-risks/healthy-bones (accessed16.11.2015)
9. Grey A, Bolland M. Web of industry, advocacy, and academia in the management of osteoporosis. BMJ 2015;351:h3170.
Competing interests: No competing interests