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Background  Low fractional calcium absorption (FCA) contributes to osteoporosis but is not measured clinically, as the gold-standard method requires administration of two calcium tracers and a subsequent 24-h urine collection. We evaluated alternate methods to measure FCA, compared to the gold standard method.    Methods  We administered two stable calcium isotope tracers (~8 mg oral  44 Ca and ~3 mg intravenous  42 Ca) with breakfast to 20 fasting post-menopausal women (Cohort 1) 59 ± 7 years old with vitamin D insufficiency. We measured subsequent calcium isotope concentrations in 24-h urine samples and serum collected 1, 3 and 5 h post tracer administration during an inpatient research stay. We assessed the candidate serum estimates in a second cohort of 9 women with similar characteristics. Methods of measuring FCA were compared using correlation coefficients and Bland-Altman tests.    Results  FCA estimated from a 3-h serum sample correlated highest with the levels from the 24-h urine collection (ρ 0.78,  p  < 0.001), but explained only 58 % of the variance in FCA. The total variance explained by 3-h estimates improved to 61 % with incorporation of glomerular filtration rate (GFR). FCA estimates from the 3-h serum measurement were assessed in a second group of nine women (Cohort 2) 60 ± 7 years old. In this cohort, however, FCA estimated by 3-h serum isotope levels did not correlate with gold-standard FCA measurements, whether determined with (ρ 0.02,  p  = 0.97) or without GFR values (ρ 0.03,  p  = 0.93). By contrast, FCA in Cohort 2 correlated best with 5-h serum isotope levels (ρ 0.75,  p  = 0.02).    Conclusions  We conclude that serum isotope levels correlate with true fractional calcium absorption, but do not reliably estimate FCA when analyzed using Bland-Altman tests, compared to gold-standard methods.    Trial registration  ClinicalTrials.gov.Identifier:  NCT00933244

Can serum isotope levels accurately measure intestinal calcium absorption compared to gold-standard methods?