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Guys Need Strong Bones Too: Calcium Is Not Just for Women Anymore
Abstract & Commentary
By David Kiefer, MD. Dr. Kiefer is a Clinical Instructor, Family Medicine, University of Washington, Seattle; Clinical Assistant Professor of Medicine, University of Arizona, Tucson; and Adjunct Faculty at Bastyr University, Seattle; he reports no financial relationship to this field of study.
Synopsis: This well-designed two-year trial shows that 1,200 mg daily of calcium citrate in healthy middle-aged men translates into higher bone mineral density and fewer falls, expanding on a body of evidence that had been focused primarily on the use of calcium in women and osteoporosis.
Source: Reid IR, et al. Randomized controlled trial of calcium supplementation in healthy, nonosteoporotic, older men. Arch Intern Med 2008;168:2276-2282.
This was a randomized, double-blind trial comparing lumbar spine bone mineral density (BMD), the primary endpoint, in 323 healthy, community-dwelling men (average age of 56 years) given two dosages of calcium citrate (600 mg daily or 600 mg twice daily) with placebo over two years. At six-month intervals, a DEXA scan was used to estimate lumbar spine, hip, and total body BMD, and other parameters were measured including number of falls and fractures, grip strength, serum 25-hydroxyvitamin D, serum parathyroid hormone, serum alkaline phosphatase, serum P1NP, urinary calcium, and dietary calcium intake. There was good compliance over the two years, and even though 14 study participants did not complete the clinical trial, all of the data underwent an intention-to-treat analysis.
The study results showed a 1% increase in lumbar spine BMD at six months in the group supplemented with 1,200 mg of calcium daily when compared with placebo, an increase that was sustained over the rest of the study period (P = 0.005). The group receiving only 600 mg daily did not show any improvement in lumbar spine BMD compared to placebo. The 1,200 mg group also showed an increase in hip BMD, and, unlike for the lumbar BMD, this increase continued throughout the two years (0.9% increase in year 1; 0.5% increase in year 2; P < 0.001). Again, the 600 mg group did not show any difference in hip BMD when compared to placebo. Total body BMD increased 1.2% during the first six months, ending at 1.5% above baseline, in the 1,200 mg group (P < 0.001); there was no improvement over baseline for either the 600 mg group or the placebo group. All of these results were unchanged when the groups were statistically analyzed as either above or below the median dietary calcium intake of 790 mg daily.
The expected physiological responses to calcium supplementation were seen in the biochemical analyses: There were dosage-related decreases in serum parathyroid hormone, and two markers for bone turnover, serum P1NP and alkaline phosphatase, over the two years of the study. Only in the 1,200 mg group was a statistically significant increase in urinary calcium seen. Of note, the mean level of serum 25-hydroxyvitamin D for all research subjects was 32.05 ng/mL.
Adverse effects occurred with similar frequency for the three groups (P = 0.16), including clinical fractures (P = 0.43). Following up on concerns about a possible connection between calcium supplementation and serious cardiovascular events in women, the researchers found no significant difference between the treatment and placebo groups for angina (P = 0.37), myocardial infarction (P = 0.37), or sudden death (P = 0.61). The men in the 1,200 mg group had significantly fewer falls when compared to the 600 mg (P = 0.005) and placebo (P = 0.45) groups.
The authors' conclusion was that supplementation with 1,200 mg of calcium citrate daily in healthy men benefits BMD throughout the body and decreases the incidence of falls, effects that were independent of dietary calcium intake.
The prevention and treatment of osteoporosis in women is a well-established topic in medical research and clinical medicine, with dozens of clinical trials and years of experience guiding recommendations for lifestyle (i.e., weight-bearing exercise), pharmaceuticals, and dietary interventions such as calcium supplementation. The use of calcium in older men is a more recent but arguably much needed expansion of this topic.
What falls out of this clinical trial (no pun intended) are a few important lessons about the clinical use of calcium in this demographic. Although some physiological changes are seen with 600 mg of calcium citrate daily, the clinical endpoints of changes in BMD and fall rates are only seen at 1,200 mg daily doses; 1,200 mg may in fact be a threshold below which minimal, if any, benefit is seen in healthy older men. In addition, despite concerns about increased nephrolithiasis or cardiovascular events with calcium supplementation, no increased rates of adverse effects were seen in either of the calcium treatment groups. The lack of obvious risk with calcium supplementation in this well-designed trial is an important part of the risk-benefit analysis that accompanies the decision about whether to incorporate calcium, as with any possible medical intervention, into clinical practice.
There is, however, some epidemiological evidence that calcium can increase the incidence of prostate cancer. The Physicians' Health Study (a cohort of 20,885 male U.S. physicians) demonstrated a trend toward increased prostate cancer risk with increased calcium intake as estimated from five dairy foods; the high calcium intake group (> 600 mg/d) had a 32% higher risk of prostate cancer than did the low calcium intake group (< 150 mg/d).1 This result agrees with other epidemiological studies as well as with observations that countries with higher per capita dairy consumption also seem to have higher prostate cancer rates. The mechanism of this effect seems to be that a high calcium intake suppresses the formation of 1,25 dihydroxyvitamin D3 levels, a vitamin that otherwise inhibits the proliferation of cells in the prostate. Results of the current study are compelling, but further delineation between optimal calcium dosage and long-term safety is required.
There are a few reasons to have confidence in the results of this clinical trial, despite the fact that previous research on the topic of calcium supplementation in men was mostly equivocal, usually showing no difference in BMD nor fracture rates between treatment and placebo groups. In the current trial, the authors argue that the higher dose of calcium used, the more accurate means of detecting changes in BMD (by using the DEXA scan), and the larger numbers of subjects and therefore increased statistical power, all could have accounted for the observed statistically significant results.
More work is needed on this topic. Many people, such as the elderly, especially if they are in nursing homes, are vitamin D-deficient, which compromises their ability to utilize calcium and improve BMD. The subjects in this trial were relatively vitamin D-replete, so it is difficult to generalize to the effect of calcium supplementation in people who are vitamin D-deficient. In the current trial, while the subjects' mean vitamin D level was in the normal range it was low-normal, and higher levels are currently thought by many to confer optimal bone health benefits. Studies addressing this issue will also be welcome. Furthermore, though information was collected about the dietary intake of calcium, other aspects of people's lives that are relevant to fracture and fall rates and BMD, such as exercise, were not taken into account. It will be interesting to see what comes out of research into calcium supplementation in people of other demographics and when used as part of an integrative treatment approach.
1. Chan JM, et al. Dairy products, calcium and prostate cancer risk in the Physician's Health Study. Am J Clin Nutr 2001;74:549-554.