Calcium isotope ratio (δ^44/42Ca) reflects kidney function and calcium excretion but not bone mineral density or bone...

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 (δ^44/42Ca) 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.

In 301 patients (43 controls), serum and urine δ^44/42Ca were analyzed alongside bone (such as bone density) and treatment parameters.

Age, kidney function, and calcium intake significantly affected δ^44/42Ca and must be considered in interpretation. δ^44/42Ca 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 δ^44/42Ca levels (p<0.05). Osteoanabolic therapy increased δ^44/42Ca (p<0.05), whereas antiresorptive treatment had no effect. No differences in δ^44/42Ca appeared by fracture or BMD stratification, but age-adjusted δ^44/42Ca 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.

While δ^44/42Ca 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 δ^44/42Ca 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 δ^44/42Ca can contribute to individualized diagnostics and treatment monitoring in bone disease.