title: Can serum isotope levels accurately measure intestinal calcium absorption compared to gold-standard methods?
abstract: 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.
  
  
  BACKGROUND
  ClinicalTrials.gov.Identifier: NCT00933244.
authors.affiliation: Department of Medicine, University of Wisconsin School of Medicine & Public Health, Suite 4124 MFCB, 1685 Highland Avenue, Madison, WI, 53705-2281, USA. AVreede@uwhealth.org.
authors.forename: Andrew P
authors.initials: AP
authors.lastname: Vreede
authors.affiliation: Department of Pediatrics, University of Wisconsin School of Medicine & Public Health, Madison, USA. andreajones@wisc.edu.
authors.forename: Andrea N
authors.initials: AN
authors.lastname: Jones
authors.affiliation: Department of Medicine, University of Wisconsin School of Medicine & Public Health, Suite 4124 MFCB, 1685 Highland Avenue, Madison, WI, 53705-2281, USA. keh@medicine.wisc.edu.
authors.forename: Karen E
authors.initials: KE
authors.lastname: Hansen
mesh_terms: D061605:Administration, Intravenous; D000368:Aged; D015992:Body Mass Index; D062408:Breakfast; D002127:Calcium Isotopes / Q000097:blood* / Q000652:urine; D002136:Calcium, Dietary / Q000008:administration & dosage* / Q000493:pharmacokinetics; D015331:Cohort Studies; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007408:Intestinal Absorption / Q000187:drug effects*; D016014:Linear Models; D008875:Middle Aged; D017698:Postmenopause / Q000097:blood; D014807:Vitamin D / Q000097:blood; D014808:Vitamin D Deficiency / Q000097:blood
chemical_list: D002127:Calcium Isotopes; D002136:Calcium, Dietary; D014807:Vitamin D