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Updated: Jun 26, 2026

A Semi-Automated and Reproducible Biological-Based Method to Quantify Calcium Deposition In Vitro
Published on: June 2, 2022
Calculated serum calcium is an insufficient surrogate for measured ionized calcium
Mikko P Björkman1, Antti J Sorva, Reijo S Tilvis
1Clinics of Internal Medicine and Geriatrics, Helsinki University Central Hospital, POB 340, FI-00290 HUS, Helsinki, Finland. mikko.bjorkman@helsinki.fi
Abstract:
Direct measurement of serum-ionized calcium (Ca2+) is the best available method to assess 'true' calcemia because serum total calcium is confounded by serum proteins, mainly albumin. However, calculated surrogates for Ca2+, albumin-adjustment particularly, have been widely used in the literature despite their insufficiency to evaluate calcemic status accurately. Recently, a new formula, in which serum total protein instead of albumin is used for adjustment of total calcium, has been suggested for very old hospitalized patients. We compared these two surrogates for Ca2+ with the direct measurement in both frail bedridden inpatients and in a general aged population. Both surrogates were equally insufficient in detecting hypocalcemia in both patient groups. However, the sensitivity and specifity for detecting hypercalcemia by both surrogates were relatively high in the bedridden inpatients. Precise assessment of calcemic status is particularly needed in research and in detecting mild hypo- or hypercalcemia. However, the calculated surrogates for Ca2+ have consistently failed in accurate assessment of 'true' calcemia. Thus, the direct measurement of Ca2+ should be favored instead of readily available automated surrogates. Adjustments of calcium for albumin or total protein may be useful in clinical practice in excluding hypercalcemia in very old bedridden patients, only.
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