Calcium isotope composition in serum and urine for the assessment of bone calcium balance (BCaB) – results from a post-market surveillance clinical follow-up study on 2409 participants

Introduction: Calcium (Ca) isotope marker (CIM) measured in serum (δ44/42Ca-serum) and urine (δ44/42Ca-urine) have been demonstrated in earlier studies (c.f. Eisenhauer et al. 2019, David et al. 2023) with a restricted number of participants to be a sensitive, reliable and minimal invasive BCaB marker. The purpose of this surveillance study was to further refine and confirm the validity of the CIM approach to a larger randomized number of people not selected based on specific criteria, but rather showing a wide range of diseases and therapies.

Methods: The 2409 participants of this surveillance study were undergoing commercially available CIM testing by osteolabs GmbH in 2020-2023 with a respective informed consent before participation. Urine was self-collected, while blood was collected in a hospital or doctor’s office and stored for transport in suitable containers. Individual data were reported: current medical conditions, the last four years fracture history, current medication and intake of supplements e.g. vitamin D and Ca. Chemical preparation and mass-spectrometer procedures followed standardized procedures. Ca isotopes were measured using a Neptune Plus (Thermo Fisher Scientific) applying a medium mass resolution (m/Δm~4000). The sample-standard-bracketing approach was applied matching the sample to the international NIST SRM 915a standard. The Ca isotope ratio is expressed in the δ-notation as δ44/42Ca in per mill (‰) relative to the above standard. The long-term reproducibility of the Ca isotope data is ±0.06‰.

Results: Results were in full accordance with earlier interpretations of the CIM and related threshold values for BCaB. All diseases, therapies or diets, positively or negatively affecting the musculoskeletal metabolism, were sensitively reflected by a change of the CIM value in serum (δ44/42Ca-serum) and urine (δ44/42Ca-urine). Osteoporosis, osteolytic metastases, hyperthyroidism, specific medications, and antihormone therapies associated with a negative BCaB were reflected by CIM values significantly below the threshold value. Osteoprotective medications such as bisphosphonates, denosumab, and romosozumab which are associated with a positive BCaB were reflected by CIM values significantly above the threshold values. The study revealed also that the δ44/42Ca-urine of vegans is the highest compared to non-vegans possibly reflecting a low calcium intake with increased PTH secretion.

Discussion: Study results confirm that the CIM values qualify as a strong and independent marker reflecting BCaB. The high CIM sensitivity allows the early risk assessment of diseases interfering with the musculoskeletal system before symptoms appear. Furthermore, CIM qualifies for a near real-time therapy monitoring to ensure a sufficient osteoprotective therapy and contributes to a general reduction in fracture risk.

Korrespondenzadresse: Anton Eisenhauer, osteolabs GmbH, Wischhofstr. 1, 24148 Kiel, Deutschland, E-Mail: [e-mail]

Publication History

Article published online:
13 March 2024