Calcium isotope ratio (δ<sup>44/42</sup>Ca) reflects kidney function and calcium excretion but not bone mineral density or bone turnover: a cross-sectional study.
cross_sectional · Level IV
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- Also identified by DOI 10.1007/s00198-026-07935-5.
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Abstract
Calcium isotope fractionation (δ⁴⁴<sup>/</sup>⁴²Ca) was evaluated as a biomarker of bone metabolism in 301 patients. δ⁴⁴<sup>/</sup>⁴²Ca correlated with urinary calcium excretion but not with bone mineral density or fracture status. Age, kidney function, and calcium intake influenced results, limiting its diagnostic utility for osteoporosis in clinical practice. Data on Calcium isotope fractions (δ<sup>44/42</sup>Ca) in isolated bone diseases are limited. Previously proposed as a diagnostic marker in metabolic bone disorders, we now extend our findings from monogenic bone diseases to patients with osteoporosis and osteopenia. In 301 patients (43 controls), serum and urine δ<sup>44/42</sup>Ca were analyzed alongside bone (such as bone density) and treatment parameters. Age, kidney function, and calcium intake significantly affected δ<sup>44/42</sup>Ca and must be considered in interpretation. δ<sup>44/42</sup>Ca correlated strongly with urinary calcium excretion (serum: r²=0.55, urine: r²=0.20; p<0.0001) but not with bone turnover markers or BMD. Higher β-CTX were associated with low δ<sup>44/42</sup>Ca levels (p<0.05). Osteoanabolic therapy increased δ<sup>44/42</sup>Ca (p<0.05), whereas antiresorptive treatment had no effect. No differences in δ<sup>44/42</sup>Ca appeared by fracture or BMD stratification, but age-adjusted δ<sup>44/42</sup>Ca stratification showed higher urinary calcium and PTH (both p<0.0001) in individuals above the threshold, a pattern consistent with neutral or positive bone mineral balance. While δ<sup>44/42</sup>Ca reflects aspects of calcium metabolism, such as nutritional calcium supply, in this real-world setting, it failed to predict fractures or distinguish osteoporosis from healthy controls or osteopenia and vice versa, indicating limited clinical use. Thus, although δ<sup>44/42</sup>Ca is a parameter of interest for calcium metabolism, it does not substitute established bone diagnostics such as BMD or laboratory assessments. Future studies are needed to determine if and how δ<sup>44/42</sup>Ca can contribute to individualized diagnostics and treatment monitoring in bone disease.