The United States preventive services task force (USPSTF) recently threw cold water on the use of calcium and vitamin D supplements to prevent fractures in adults, either finding inadequate evidence to make a recommendation or recommending against supplementation, depending on the population and the doses used.1
Complicating this issue, several recent studies have raised concern about the long-term cardiovascular risk of calcium supplementation.
With so many people taking calcium supplements, how do we put this into context for our patients? I believe that we need to consider the whole person when discussing these supplements, as there are data that they also help reduce the risk of falls, cancer, and even overall mortality rates.
THE USPSTF’S METHODS
The USPSTF bases its recommendations on explicit criteria2 developed by its Evidence-based Practice Center, which is under contract to the US Agency for Healthcare Research and Quality to conduct systematic reviews of the evidence on specific topics in clinical prevention. The USPSTF grades the strength of the evidence for the effectiveness of specific clinical preventive services as:
- A (strongly recommended)
- B (recommended)
- C (no recommendation)
- D (recommended against)
- I (insufficient evidence to make a recommendation for or against).
USPSTF recommendations consider the evidence of both benefit and harm of the intervention but do not include the cost of the intervention in the assessment.3
THE USPSTF’S GRADES ON CALCIUM AND VITAMIN D SUPPLEMENTATION
The USPSTF made the following recommendations in February 2013 about the use of calcium and vitamin D supplementation:
- For primary prevention of fractures in premenopausal women and men: grade I (current evidence is insufficient to assess the balance of the benefits and harms)
- For primary prevention of fractures in noninstitutionalized postmenopausal women, in daily doses greater than 400 IU of vitamin D and greater than 1,000 mg of calcium: also grade I
- For primary prevention of fractures in noninstitutionalized postmenopausal women, in daily doses of 400 IU or less of vitamin D and 1,000 mg or less of calcium: grade D (the USPSTF recommends against it, as these doses increase the incidence of renal stones and there is “adequate” evidence that these doses have no effect on the incidence of fractures).
WHAT THE USPSTF DID NOT DISCUSS
These recommendations do not apply to everybody. Rather, the document discusses “the effectiveness of specific clinical preventive services for patients without related signs or symptoms,”1 and states that the recommendations do not pertain to patients with osteoporosis or vitamin D deficiency or those who have had fractures.
Also, the document does not discuss the use of calcium supplementation by itself in fracture prevention. nor does it discuss possible benefits of calcium and vitamin D other than fracture prevention, such as reducing the risk of falls, cancer, or death. Further, the document states that “appropriate intake” of vitamin D and calcium is “essential to overall health”1 but does not state the amount that is considered appropriate.
The document does refer the reader to other USPSTF recommendations concerning screening for osteoporosis in women age 65 and older and in younger women who demonstrate the fracture risk of a 65-year-old woman,4 as well as to its recommendation for vitamin D supplementation to prevent falls in community-dwelling adults age 65 and older who are at higher risk of falls.5
Not included: A new meta-analysis
The USPSTF document also notes that after their review was completed, another metaanalysis concluded that fracture risk may be reduced by taking vitamin D in doses of 800 IU or higher.6
In that study, Bischoff-Ferrari et al6 performed a pooled analysis of vitamin D dose requirements for fracture prevention from 11 double-blind, randomized, controlled trials of oral vitamin D supplementation taken either daily or at weekly or 4-month intervals with or without calcium, compared with placebo or calcium alone in people age 65 and older. The primary end points were the incidence of hip fracture and any nonvertebral fracture according to Cox regression analysis, with adjustment for age, sex, community or institutional dwelling, and study. The aim was to evaluate actual vitamin D intake rather than the assigned dosage groups in the trials.
On the basis of actual vitamin D intake, the incidence of hip fracture was significantly (30%) lower in people with the highest actual intake (792–2,000 IU per day) than in controls. There was no reduction in the risk of hip fracture at any actual intake levels lower than 792 IU per day. Using this same analytic technique, the reduction in the incidence of nonvertebral fracture at the highest actual intake level was 16%.
Why were their findings different than those of the USPSTF? The authors hypothesized that some previous high-quality trials of vitamin D supplementation either showed no benefit because the participants were noncompliant and thus took less than the intended dose of vitamin D, or showed an unexpected benefit because the participants actually took more vitamin D than was specified in the study.
The USPSTF recommendations did not include studies of vitamin D without calcium, whereas Bischoff-Ferrari et al did, which could also explain some of the differences in the findings, as not all of the studies included in the two documents were the same. Several previous meta-analyses suggested that the dose of vitamin D was irrelevant when vitamin D was combined with calcium.
The data from Bischoff-Ferrari et al suggested that at the highest actual intake level of vitamin D, a smaller amount of calcium supplementation (< 1,000 mg daily) may be more beneficial in reducing fracture risk than a larger amount (≥ 1,000 mg daily). This is important, given the current level of concern initially raised by Bolland et al7 and others about the possible risks of higher doses of calcium supplements increasing cardiovascular risk. (More on this below.)