Higher Calcium Intake May Not Lower Risk for Fractures and Osteoporosis

 Gradual increases in dietary calcium intake above the first quintile in a large female cohort are not associated with further reductions in fracture risk or osteoporosis, according to the results of a prospective longitudinal cohort study reported in the May 24 issue of the BMJ.

"It is problematic to make recommendations regarding calcium intake based on the results from clinical trials and previous cohort studies," write Eva Warensjö, from Uppsala University in Uppsala, Sweden, and colleagues. "Meta-analyses of randomised trials found that supplemental calcium gave modest or no reduction in risk of fracture. Both the habitual dietary intake of calcium and vitamin D status may affect the outcome and are rarely accounted for in the design of calcium supplementation trials."
The goal of the study was to evaluate associations between long-term dietary calcium intake and the risk for any type of fractures, hip fractures, and osteoporosis. The study cohort consisted of 5022 women who participated in a subcohort of the Swedish Mammography Cohort of 61,433 women in Sweden who were born between 1914 and 1948. This population-based cohort was established in 1987, and participants were followed up for 19 years for primary outcomes of incident fractures of any type and hip fractures, which were identified from registry data.
A secondary outcome in the subcohort was osteoporosis diagnosed by dual energy x-ray absorptiometry. Repeated food frequency questionnaires allowed determination of dietary consumption.
Of 14,738 women (24%) who had a first fracture of any type during follow-up, 3871 (6%) had a first hip fracture. Osteoporosis was diagnosed in 1012 (20%) of the subcohort. For dietary calcium, the risk patterns were nonlinear. In the lowest quintile of calcium intake, the crude rate of a first fracture of any type was 17.2/1000 person-years at risk vs 14.0/1000 person-years at risk in the third quintile, yielding a multivariable adjusted hazard ratio (HR) of 1.18 (95% confidence interval [CI], 1.12 - 1.25). For a first hip fracture, the HR was 1.29 (95% CI, 1.17 - 1.43), and the odds ratio for osteoporosis was 1.47 (95% CI, 1.09 - 2.00).
The fracture rate in the first calcium quintile was more pronounced with a low vitamin D intake. Although the highest quintile of calcium intake did not further lower the risk for fractures of any type, or the risk for osteoporosis, it was associated with a higher rate of hip fracture (HR, 1.19; 95% CI, 1.06 - 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," the study authors write.
Limitations of this study include possible residual confounding; limitations inherent in dietary assessment methods; observational design, precluding conclusions regarding causality; and lack of generalizability to other people of different ethnic origins or to men.
"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 study authors conclude. "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."

The Swedish Research Council supported this study. The study authors have disclosed no relevant financial relationships.
BMJ. 2011;342:d1473. Abstract

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Clinical Context

Osteoporotic fractures are frequent in older women. There is a wide range of recommendations for daily supplementation ranging from 700 mg daily in the United Kingdom to 1200 mg daily in the United States. However, meta-analyses of trials have shown no reduction in fracture risk with calcium supplementation.
This is an observational cohort study of women in Sweden to examine the association between long-term dietary calcium intake and the risk for fractures and osteoporosis in women.

Study Highlights

• Included were 61,433 women in the Swedish Mammography Cohort established in 1987 to 1990, who completed a baseline food frequency questionnaire.
• Fracture events were ascertained through linkage with the Swedish National Registry; International Classification of Diseases, 10th Revision, codes for fractures were used.
• Primary outcomes were rate of first fracture and rate of hip fractures.
• Between 2003 and 2005, a subcohort of women (n = 5022) received dual energy x-ray absorptiometry scans of the hip, spine, and whole body. This cohort was used to assess the risk for osteoporosis.
• Osteoporosis was defined as a bone mineral density of 2.5 or more SDs for the mean of a young adult.
• Nutrient data were obtained from the Swedish National Food Administration database and adjusted for total energy intake.
• For the entire cohort, mean age at entry was 54 years, body mass index was 24.7 kg/m², average energy intake was 1626 kcal, alcohol intake was 3.1 g, and 25% were smokers.
• Increasing intake of calcium was associated with increasing intake of other nutrients.
• At a median of 19.2 years of follow-up and 996,800 person-years of risk, 14,738 (24%) of women experienced any type of first fracture, and 5043 (8%) experienced 2 or more fractures.
• For hip fractures, the rate was 6% for first fracture and 2% for more than 1 hip fracture.
• In the subcohort, 1012 (20%) of women were classified as having osteoporosis.
• There was a nonlinear decrease in the risk for fractures for every 300-mg increase in daily calcium intake.
• The rate of fractures and osteoporosis was highest in the lowest quintile of calcium intake, with a multivariate adjusted HR of 1.18 (95% CI, 1.12 - 1.25) for any fracture and 1.29 (95% CI, 1.17 - 1.43) for hip fracture.
• Within the lowest quintile of calcium intake, for every 100-mg decrease in calcium intake, the risk for fracture increased with a multivariate HR of 1.08 (95% CI, 1.04 - 1.11) for any first fracture and 1.07 (95% CI, 1.01 - 1.13) for hip fracture.
• There was also an increase in the risk for osteoporosis in the lowest quintile of calcium intake, with a decrease in calcium intake (adjusted odds ratio, 1.47; 95% CI, 1.09 - 2.00).
• In the highest quintile of calcium intake, the rates of fractures and hip fracture were similar to that of the third quintile.
• Although the highest quintile of calcium intake did not further reduce the risk for fractures of any type, or the risk for osteoporosis, the rate of hip fractures was increased in the highest quintile (HR, 1.19; 95% CI, 1.06 - 1.32).
• Quintile of calcium intake and calibrated calcium intake did not change the estimated HRs for fractures.
• Vitamin D intake modified the associations and increased hip fracture rate in the lowest quintile of intake.
• The authors concluded that dietary intake of calcium was associated with the risk for fractures and osteoporosis only in the lowest quintile of intake.
• They suggested that in the prevention of osteoporotic fractures, emphasis should be given to individuals with a low intake of calcium rather than those consuming adequate amounts of calcium.

Clinical Implications

• For women with the lowest intake of dietary calcium, increasing calcium intake is associated with a decreased risk for any type of fracture, hip fracture, and osteoporosis.
• In women with high and adequate dietary calcium intakes, increasing calcium intake does not further reduce the risks for fracture, hip fracture, and osteoporosis.

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