Calcium isotope ratio in patients with monogenic bone diseases: a prospective, cross-sectional, single-center pilot study.

Stable calcium isotope fractions have long been related to the calcium metabolism in living organisms. The blood and urine proportions of calcium isotopes Ca and Ca (δCa) have recently again attracted attention as a potential diagnostic tool in metabolic bone diseases, in particular osteoporosis. The hypothesis is that the lighter isotopes (Ca) get incorporated into bone more quickly; hence, δCa ratios in urine and serum are higher for bone formation and lower for resorption phases. Therefore, δCa in blood and urine may serve as an indicator of bone metabolism, potentially reflecting bone density in general. We have conducted clinical characterization by means of laboratory assessment, bone densitometry, HRpQCT, and isotope analysis to test for the hypothesis in patients with monogenic bone diseases. We included 40 adult subjects with hereditary bone diseases, such as early-onset osteoporosis ( = 7), osteogenesis imperfecta ( = 12), hypophosphatasia ( = 12), and X-linked hypophosphatemia (XLH,  = 9), and controls ( = 17). Regression analyses revealed significant correlations of δCa with Ca/creatinine (  = 0.6200,  < .0001), and bone densitometric parameters were significantly correlated with δCa (BMD: δCa    = 0.2685,  ≤ .001; δCa    = 0.3554;  < .0002). XLH differed significantly from the other diseases and controls by means of higher δCa. Our results suggest that δCa is strongly coupled to urinary calcium excretion in patients with hereditary bone diseases. Significant correlations with BMD suggest an interaction of δCa and bone mass though it lacks discriminative power. Further studies are needed to evaluate the utility of δCa in clinical practice.