Increasing calcium intake does not prevent fractures

Calcium is still, contrary to the best available evidence, often recommended to reduce fracture risk. Research just published in BMJ (British Medical Journal) adds more evidence that increasing calcium intake by diet or supplementation does not prevent fractures. The authors conducted a systematic review of randomized controlled trials and observational studies...

"To examine the evidence underpinning recommendations to increase calcium intake through dietary sources or calcium supplements to prevent fractures."

Besides evaluating recommendations to increase dietary calcium intake to prevent fractures, they compared the anti-fracture effect of increasing calcium through dietary sources with the efficacy of calcium supplements by compiling data from randomized controlled trials or cohort studies of dietary calcium, milk or dairy intake, or calcium supplements (with or without vitamin D) with fracture as an outcome in subjects over 50.

No significant fracture reduction from dietary or supplemental calcium

When the data were thoroughly examined the evidence for efficacy of calcium intake vanished.

"There were only two eligible randomised controlled trials of dietary sources of calcium (n=262), but 50 reports from 44 cohort studies of relations between dietary calcium (n=37), milk (n=14), or dairy intake (n=8) and fracture outcomes. For dietary calcium, most studies reported no association between calcium intake and fracture (14/22 for total, 17/21 for hip, 7/8 for vertebral, and 5/7 for forearm fracture). For milk (25/28) and dairy intake (11/13), most studies also reported no associations. "

As for supplements...

"In randomised controlled trials at lowest risk of bias (four studies, n=44 505), there was no effect on risk of fracture at any site. Results were similar for trials of calcium monotherapy and co-administered calcium and vitamin D. Only one trial in frail elderly women in residential care with low dietary calcium intake and vitamin D concentrations showed significant reductions in risk of fracture."

Osteoporosis is not a calcium deficiency disorder

Clinicians involved in case management of osteoporosis and osteopenia know (or should know) that these disorders are due to failure to maintain the protein matrix of the bone, the component that provides resilient strength and to which the minerals attach, not a deficiency of the minerals themselves, including calcium. (Calcium deficiency, or osteomalacia, is also known as 'rickets.') The authors comment further on their findings regarding diet:

"The recommended dietary calcium intake for older adults is 1200 mg/day.Most studies, however, did not report Creduced risk of fracture in individuals with this level of calcium intake compared with lower intakes. Thus, observational research does not support a hypothesis of dietary “calcium deficiency” in which there are reductions in fracture risk from increasing dietary calcium intake across the range of intakes (<300->1200 mg/day) in studies in this review."

And...

"There was no effect of calcium supplements on any fracture outcome in the largest trials at lowest risk of bias. ...These results suggest that widespread untargeted use of calcium supplements in older individuals is unlikely to result in meaningful reductions in incidence of fracture."

As the authors note:

"...it should not be assumed that short term changes in bone density will be sustained or translate into fracture prevention."

Calcium and cardiovascular risk

Calcium supplementation has been associated with increased cardiovascular risk (see Calcium supplements increase risk of heart attack), probably by opposing the anti-inflammatory effects of magnesium. The authors comment on this and other risks:

"In our randomised controlled trial and subsequent meta-analyses, the cardiovascular risks of calcium were similar to or exceeded the benefits of calcium on fracture prevention. In addition, 10-20% of people experience gastrointestinal side effects such as constipation, which cause a considerable number to stop taking the supplements. Thus, because of the small benefits of use and unfavourable risk:benefit profile, calcium supplements should not be recommended for fracture prevention either at an individual or population level."

Regarding the one study with elderly frail women...

"...it is possible that many participants had unrecognised osteomalacia, the treatment of which might have led to the benefits observed...Our analyses highlight that the results from this study of a frail population with marked vitamin D deficiency are so different to those from other large randomised controlled trials and so influential in any pooled analysis that they should probably not be combined in pooled analyses with studies that enrolled different patient groups. Furthermore, recommendation of use of calcium and vitamin D supplements generally for older adults to prevent fracture based on results heavily influenced by this study of frail women in residential care is inappropriate."

Do not recommend calcium to patients for osteoporosis fracture risk

Medscape Medical News reports in regard to this research:

"This is not the first recent review to find a lack of evidence for calcium supplements. The US Preventive Services Task Force reached similar conclusions in 2013."The question is not so much why the guidelines were formed, but why is it, since there have been all these trials accumulated since 2000, they haven't changed," Dr Bolland [lead author] said."

The authors conclude:

"On the basis of the trial data summarised here, we do not think further randomised controlled trials of calcium supplements with or without vitamin D with fracture as the endpoint in the general population are needed...our analyses indicate that dietary calcium intake is not associated with risk of fracture, and there is no evidence currently that increasing dietary calcium intake prevents fractures....There was no risk reduction in fracture at any site in pooled analyses of the randomised controlled trials of calcium supplements at lowest risk of bias, and there was evidence of publication bias in small-moderate sized trials. Collectively, these 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."

No significant improvement through bone mineral density either

Additional research in the same issue of BMJ examined data for the effects of calcium intake on BMD (bone mineral density) and found no meaningful benefit.

"Increasing calcium intake from dietary sources increased BMD by 0.6-1.0% at the total hip and total body at one year and by 0.7-1.8% at these sites and the lumbar spine and femoral neck at two years. There was no effect on BMD in the forearm. Calcium supplements increased BMD by 0.7-1.8% at all five skeletal sites at one, two, and over two and a half years, but the size of the increase in BMD at later time points was similar to the increase at one year. Increases in BMD were similar in trials of dietary sources of calcium and calcium supplements (except at the forearm), in trials of calcium monotherapy versus co-administered calcium and vitamin D, in trials with calcium doses of ≥1000 versus <1000 mg/day and ≤500 versus >500 mg/day, and in trials where the baseline dietary calcium intake was <800 versus ≥800 mg/day."

Based on this the authors of the BMD study conclude:

"In summary, increasing calcium intake from dietary sources increases BMD by a similar amount to increases in BMD from calcium supplements. In each case, the increases are small (1-2%) and non-progressive, with little further effect on BMD after a year. Subgroup analyses do not suggest greater benefits of increasing calcium intake on BMD in any subpopulation based on clinically relevant baseline characteristics. The small effects on BMD are unlikely to translate into clinically meaningful reductions in fractures. Therefore, for most individuals concerned about their bone density, increasing calcium intake is unlikely to be beneficial."

Perverse influence of industry

In an accompanying editorial, the author comments on the use of guidelines that are contrary to the scientific evidence:

"By use of guidelines such as those by NOF and the International Osteoporosis Foundation (IOF), marketing now extends to all older people with dietary intakes below the recommended 1200 mg calcium and 800-1000 IU vitamin D daily. By this definition virtually the whole population aged over 50 is at risk.Most will not benefit from increasing their intakes and will be exposed instead to a higher risk of adverse events such as constipation, cardiovascular events, kidney stones, or admission for acute gastrointestinal symptoms.The weight of evidence against such mass medication of older people is now compelling, and it is surely time to reconsider these controversial recommendations...The profitability of the global supplements industry probably plays its part, encouraged by key opinion leaders from the academic and research communities. Manufacturers have deep pockets, and there is a tendency for research efforts to follow the money (with accompanying academic prestige), rather than a path defined only by the needs of patients and the public. The research agenda and recommendations can also be influenced by the conflicts of interest that arise when leading academics have shares or management positions in companies making and marketing supplements."

A New England Journal of Medicine Journal Watch interview with lead author Dr. Mark Bolland can be heard here.

Interview on investigation into the flawed U.S. dietary guidelines

From BMJ.com: