5/10/17: OSTEOPOROSIS: The Association Between Calcium Intake and Cardiovascular Disease; Do Calcium Supplements Help to Prevent Fractures?

osteoporosis

Last year, an expert panel convened by the National Osteoporosis Foundation (NOF) and the American Society for Preventive Cardiology (ASPC) concluded that, in light of the available evidence to date, calcium intake from food and supplements that does not exceed “the tolerable upper level of intake”—defined as 2000 to 2500 mg per day—does not pose a risk of cardiovascular disease (CVD) in generally healthy adults.

The panel took up the issue of calcium intake and the CVD risk it poses, if any, after a prominent meta-analysis of data from randomized trials had suggested that calcium, with or without vitamin D supplementation, increases the risk of myocardial infarction and stroke. No postmenopausal woman taking calcium supplements to fortify her bones wants to increase her risk of a heart attack.

More recently, however, another meta-analysis had concluded that calcium, with or without vitamin D, has no statistically significant effects on coronary heart disease or mortality.

In the face of conflicting evidence, the NOF contracted with an “independent” evidence review team at Tufts University to update and reanalyze all existing evidence on calcium intake and cardiovascular disease risk. The NOF also funded the team’s work.

Upon receiving the Tufts team’s assessment, the NOF-ASPC panel concluded that “moderate-quality evidence (B level)” exists to establish that calcium, with or without vitamin D intake from food or supplements, “has no relationship . . . to the risk for cardiovascular and cerebrovascular disease” or “all-cause mortality” in healthy adults.

Both the quantification of the safe level of daily calcium intake and the “B level” grading of the evidence on the association between calcium and CVD risk formed a joint position statement adopted in July 2016 by the boards of directors of the NOF and ASPC.

This joint statement would seem to be a fairly big deal for those of us who have lost—or are at risk of losing—bone mass, and for the clinicians who advise us. I’m sorry to say that my gynecologist missed it.

***

Like many postmenopausal women, I have osteopenia—in spite of doing regular resistance and weight-bearing exercise for decades, as well as taking other precautions to protect my bones. Osteopenia is also known as low bone mass, which is bone loss that is abnormal, but not as severe as osteoporosis.

With age, our bones lose minerals and become less dense: They lose mass. A drop in blood-estrogen levels accelerates bone thinning in postmenopausal women, but men experience bone loss and osteoporosis, too, especially after age 70 when their testosterone diminution is significant.

Low bone mineral density (BMD), particularly at the hip (femoral neck), is a strong risk factor for fractures. A woman’s BMD is assessed by dual energy X-ray absorptiometry (DEXA) scans of her hips and spine, which produce T-scores that compare her bone density to the average bone density of young healthy women. The T-score range for normal bone mass is +1 to -1; for low bone mass, -1 to -2.5 (osteopenia); and for osteoporosis, -2.5 or lower.

In 2010, a team of governmental and academic medical researchers, including the CDC, estimated that 57 percent of adults in the United States age 50 and older had low bone mass or osteoporosis. See https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4757905/.

(There are many lifestyle-related and other significant risk factors, besides inadequate physical activity, for low bone mass and osteoporosis. In my case, a family history of osteoporosis and fractures applies. I am also a diehard coffee drinker. See my 5/10/17 Tidbit item for a list of risk factors.)

Osteoporosis, according to Georgetown Associate Professor Andrea J. Singer, an obstetrician-gynecologist who specializes in the bone disease, is a “skeletal disorder characterized by compromised bone strength predisposing to an increased risk of fracture.”

Bone strength, said Singer, whom I heard lecture at Georgetown last week, equals bone density (“quantity”) plus bone quality (“micro-architecture, etc.”). We reach our peak bone density at age 30.

I thought my gynecologist was on the cutting edge when she discouraged me last fall from taking calcium supplements and referred me to a report by researchers from Johns Hopkins Medicine and other elite U.S. academic institutions who had concluded that “excess calcium in the form of supplements may harm the heart and vascular system.”

Indeed, I cited this report, which was published in The Journal of the American Medical Assn., in a 10/19/16 Tidbit item. I even quoted the principals as suggesting that taking calcium supplements may raise the risk of plaque building up in the coronary arteries and, thus, damage the heart.  

I was eager to learn what Professor Singer, a nationally recognized expert in osteoporosis, thought about the benefits and harms of calcium intake. When she cited the NOF-ASPC joint position statement, I was surprised. I had never heard of it. I immediately asked her about the contradictory Johns Hopkins research, and she replied by faulting that study’s methodology and calling its conclusions “wrong.”

***  

One chief problem, Singer said, was that the Johns Hopkins data were culled from a 10-year study of atherosclerosis, not osteoporosis. The Hopkins analysis did not examine how people with osteoporosis—which is a chronic systemic disease—fared with or without varying levels of calcium supplementation. In fact, the Georgetown professor emphasized, cardiovascular outcomes have not been the “primary end point” of any trial investigating calcium or calcium and vitamin D supplementation. Until such time as such a study is done, the benefits and harms of calcium intake on the cardiovascular and cerebrovascular systems will not be truly known.

Dr. Singer is clinical director of the NOF and was one of the nine members of the advisory expert panel. What, if any, horse she might have in the osteoporosis research stakes, I couldn’t tell you. She is a consultant to a number of pharmaceutical companies and is aware of the R&D status of experimental new osteoporosis drugs. She also stands by her review of the Tufts team’s conclusions.

The Tufts team came up with the recommended tolerable upper intake range of calcium (2000 to 2500 mg/d), and the other positions that the panel accepted, after assessing the “internal validity, precision of risk estimates, and consistency of results from [available] randomized trials and prospective cohort studies.” You may read about its review at http://annals.org/aim/article/2571713/calcium-intake-cardiovascular-disease-risk-updated-systematic-review-meta-analysis.

Conflicting conclusions across several meta-analyses—which statistically combine data from multiple studies—can cause uncertainty in the healthcare community and confusion among the public, especially for those of us with, or at risk of, the condition being addressed.

The bottom line here is that there is currently no established biological mechanism to support an association between calcium and cardiovascular disease.

***

Besides the question of calcium’s association with heart disease, there is the more fundamental question of whether calcium supplementation provides any benefit to older adults who are concerned about their bone mass. Systematic reviews of existing evidence have been inconsistent about whether calcium and vitamin D supplementation reduces the risk for fracture in older adults. In fact, the question of whether calcium and vitamin D intake, especially through supplements, is efficacious in increasing bone-mineral density or in preventing osteoporotic fractures has long been a controversial one.

Bone is a living tissue that continuously renews itself by replacing old and damaged bone with new bone. Calcium constitutes some of the material of the “matrix” that surrounds widely separated bone cells and is an essential nutrient for maintaining bone health.

As the Tufts researchers explain: “A small proportion of total body calcium [less than 1 percent] also regulates vascular contraction and vasodilation, muscle function, nerve transmission, intracellular signaling, and hormonal secretion. Vitamin D promotes calcium absorption in the gut and maintains adequate serum calcium and phosphate concentrations, enabling normal bone mineralization and preventing hypocalcemic tetany.”

(Hypocalcemic tetany is a disease caused by an abnormally low level of calcium in the blood. It is characterized by hyperexcitability of the neuromuscular system and results in painful muscular spasms, often in the hands and feet. A common cause of this disease is a deficiency in parathyroid hormone secretion.)

Despite the known importance of calcium and vitamin D in bone health, the role of their supplementation in older adults, the Tufts team and Dr. Singer agree, “is unclear.” So, why are so many older adults, especially women, popping calcium pills every day?

I think the answer is: To cover all of the bases.

In a 2/4/16 Tidbit item, I passed along what I thought was useful information about osteoporosis from two epidemiologists, Drs. Dennis M. Black and Clifford J. Rosen, who had published an overview of postmenopausal osteoporosis in The New England Journal of Medicine. Black and Rosen advised postmenopausal women with osteoporosis to take 1000 to 1500 mg of calcium per day.

This dosage turns out to be essentially the recommended calcium intake for all women and men, regardless of their age and bone density and quality, according to the Institute of Medicine, as reported by Dr. Singer.

The IOM recommends that women age 50 and younger consume 1000 mg daily of calcium and that women age 51 and older consume 1200 mg daily. As for men, the age dividing line is 70, but the numbers are the same: 1000 mg daily for men age 70 and younger and 1200 mg for men age 71 and older. In all cases, calcium intake includes dietary sources, plus supplements, and the IOM recommends that the intake be in divided doses.

The NOF-ASPC position statement further advises that:

+It is preferable to obtain calcium from food sources.

+Supplemental calcium can be safely used to make up any shortfall in dietary intake.

+Discontinuation of supplemental calcium for safety reasons is not necessary and may be detrimental to bone health in situations where intake from food is suboptimal.

+People should aim to reach, but not exceed, recommended intakes.

About 75 to 80 percent of calcium in American diets comes from dairy products, such as milk, cheese, and yogurt. Leafy green vegetables and some nuts, such as almonds, are other good sources.

I’m still banking on exercise.

Ann, 5/10/17 

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