(2002) study are the most reliable of the values in this analysis. Two additional values taken from Heaney et al. (2003) in this graphic analysis (at approximately 50 and 85 nmol/L) are not direct measures of calcium absorption, but instead are indirect pharmacokinetic measures based on the plasma calcium response to a 500 mg oral calcium load (Heaney et al., 2003). Thus, the committee found these values limited in their usefulness in this analysis. The remaining 25OHD level of a calcium absorption of 0.15 at serum 25OHD 29 nmol/L was taken from Bischoff et al. (2003). It does not represent either a direct or indirect measurement of calcium absorption, but was derived from measured urinary calcium excretion using subjects that did not reduce serum PTH while on calcium supplements (Heaney, 2005; personal communication, R. P. Heaney, Creighton University, Omaha, NE, August 25, 2009). This approach is not generally acceptable, and the committee could not consider the value to be valid. In conclusion, the portion of this analysis showing a rise in calcium absorption with an increase in 25OHD level from approximately 28 nmol/L to 80 or 90 nmol/L is unreliable, because the two values showing this rise either are not based on directly measured calcium absorption or are based on an unreliable method for estimating calcium absorption as discussed by Aloia et al. (2010) and as described below. The remaining two values, although reliable, are insufficient to determine the relationship of 25OHD level to calcium absorption, if any exists.
The gold standard for assessing fractional calcium absorption is to administer two calcium isotopes (one orally, one intravenously) under conditions in which blood and/or urine can be collected and assayed for both isotopes. Alternatively, calcium absorption can be assessed using a single isotope test, although results may be less precise. As discussed below, the data from studies published after the Heaney (2005) paper either do not show increased calcium absorption with higher levels of 25OHD or show only a very slight increase in calcium absorption as serum 25OHD level rises.
With respect to children, Abrams et al. (2009) performed dual-label calcium absorption studies in 251 children ranging from 4.9 to 16.7 years of age and found no effect of higher serum 25OHD level on fractional calcium absorption. In fact, children with 25OHD levels of 28 to 50 nmol/L had higher fractional calcium absorption than did children with 25OHD levels of 50 to 80 or greater than 80 nmol/L. Data from a 2008 study in girls (Weaver et al., 2008) indicated that serum 25OHD level did not predict net calcium absorption and retention. A study conducted in Nigeria (Thacher et al., 2009) demonstrated that in children with rickets, increases in serum 25OHD level did not coincide with increased fractional calcium absorption.
With respect to adults, there are a number of single-isotope studies of