High-throughput measurement of Ca by accelerator mass spectrometry to quantitate small changes in individual human bone turnover rates

Biochemical markers of bone turnover suffer from large analytical and natural fluctuations (20–30%), making small differences in bone resorption impossible to resolve. This limits the clinical utility of such markers for individuals with the skeletal complications associated with many disease states (e.g., metastatic cancer, renal failure, osteoporosis). We are developing the capability to measure small changes (5–10%) in bone turnover rate in vivo by tagging the living skeleton with ⁴¹Ca. Among the stable and radioactive calcium isotopes, only ⁴¹Ca is useful for direct quantitation of bone turnover because it is extremely rare in nature and radiologically benign (10⁵ years half-life, pure electron capture decay). The ratio of this tracer to total calcium remains quantifiable in body fluids and excreta via accelerator mass spectrometry (AMS) for many years following a single physiological-sized oral or intravenous dose. The highly automated AMS instrumentation and streamlined sample preparation allows a single operator to prepare or run more than 100 samples per day—significantly more than other ⁴¹Ca programs worldwide. We intend to exploit these measurements for earlier diagnosis of pathological processes and interactive intervention with therapeutic agents, allowing modulation of these agents to obtain the best individual result for a patient.