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Summary <p>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.</p> Methods <p>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.</p> Results <p>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&lt;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&lt;0.05). Osteoanabolic therapy increased δ<sup>44/42</sup>Ca (p&lt;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&lt;0.0001) in individuals above the threshold, a pattern consistent with neutral or positive bone mineral balance.</p> Conclusion <p>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.</p>

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Calcium isotope ratio (δ44/42Ca) reflects kidney function and calcium excretion but not bone mineral density or bone turnover: a cross-sectional study

  • 期刊论文

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  • 发表日期：

    2026年4月11日

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  • Felix N. von Brackel,
  • Mikolaj Bartosik,
  • Robert Munzinger,
  • Florian Barvencik,
  • Thorsten Schinke,
  • Ralf Oheim,
  • Michael Amling

摘要

Summary

Calcium isotope fractionation (δ⁴⁴/⁴²Ca) was evaluated as a biomarker of bone metabolism in 301 patients. δ⁴⁴/⁴²Ca 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 (δ44/42Ca) 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.

Methods

In 301 patients (43 controls), serum and urine δ44/42Ca were analyzed alongside bone (such as bone density) and treatment parameters.

Results

Age, kidney function, and calcium intake significantly affected δ44/42Ca and must be considered in interpretation. δ44/42Ca 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 δ44/42Ca levels (p<0.05). Osteoanabolic therapy increased δ44/42Ca (p<0.05), whereas antiresorptive treatment had no effect. No differences in δ44/42Ca appeared by fracture or BMD stratification, but age-adjusted δ44/42Ca 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.

Conclusion

While δ44/42Ca 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 δ44/42Ca 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 δ44/42Ca can contribute to individualized diagnostics and treatment monitoring in bone disease.