Study of the Diagnostic Value of Stable Calcium Isotope Profiling in Bone and Calcium Disorders

NCT02252679 — Completed, 54 participants, Universitaire Ziekenhuizen KU Leuven

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Endogenous Calcium Stable Isotope Study (eCaSIS): Evaluation of MC-ICP-MS as a Diagnostic Tool for Metabolic Bone Diseases and Disorders of Calcium Metabolism

Registry	NCT02252679, acronym eCaSIS
Status	Completed
Study type	Observational
Enrollment	54 (Actual)
Sponsor	Universitaire Ziekenhuizen KU Leuven (Other); collaborators: GEOMAR-Helmholtz Centre for Ocean Research
Conditions	Bone Diseases, Osteomalacia, Osteoporosis
Dates	start 2014-10-01, primary completion 2018-12-01, completion 2018-12-01, first posted 2014-09-30, last updated 2020-11-06
Locations	2 sites in Belgium, Germany

-Summary

The purpose of this study is to determine whether mass spectrometry analysis of stable (non-radioactive) calcium isotopes in plasma or urine samples can help in the diagnosis of bone and calcium disorders.

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+Detailed description

The aim of this pilot study is to explore the diagnostic value of MC-ICP-MS (multicollector inductively coupled plasma mass spectrometry) or TIMS (thermal ionization mass spectrometry) measurement of endogenous stable calcium isotopes in plasma and urine samples in patients seen during routine clinical care at the outpatient clinics (incl. Center for Metabolic Bone Diseases) of the University Hospitals Leuven.

+Arms and interventions

Arm	Type	Interventions	Description
Osteoporosis			Postmenopausal women, men > age 50 years, or other patients with well-established causes of secondary osteoporosis (incl. glucocorticoid-induced osteoporosis, transplantation-related osteoporosis, disuse osteoporosis, etc.) N=20 treated with antiresorptive drugs N=10 treated with osteoanabolic drugs (e.g. teriparatide, Forsteo)
Calcium malabsorption			N=10 Patients with clinically obvious potential causes of calcium malabsorption (incl. severe vitamin D-deficiency, Scopinaro or other bariatric surgery, exocrine pancreatic insufficiency/steatorrhea, cystic fibrosis, inflammatory bowel disease, celiac disease, anorexia nervosa/eating disorders, malnutrition, etc.), with or without bone pains, muscle weakness and other typical osteomalacia symptoms. Confirmed by 24h urine collection showing calciuria <100 mg/24h.
Various disorders			Exploratory, heterogeneous group of calcium-related disorders (incl.hypercalcemia, hypocalcemia, primary/secondary/tertiary hyperparathyroidism, hypoparathyroidism, vitamin D deficiency, X-linked/autosomal dominant hypophosphatemic rickets, familial hypocalciuric hypocalcemia,etc.) N=20
Normal control subjects			N=40 Men and women ≤ 40 years recruited from the population

+Outcome measures

Primary outcomes

Likelihood ratio (LR) of urinary calcium δ44/40 Ca (‰) values for diagnosing negative skeletal calcium balance [follow-up will vary on clinical basis, with expected averages of 1 year (for osteoporosis) to 3 months (for other conditions)]: The sensitivity, specificity, positive and negative predictive value of the new test will be compared to expert clinical diagnosis as the gold standard. This diagnosis is established during follow-up and based on clinical observations, bone mineral density results/changes, bone turnover markers and response to treatments.

Secondary outcomes

Likelihood ratio (LR) of plasma calcium δ44/40 Ca (‰) values for diagnosing negative skeletal calcium balance [follow-up will vary on clinical basis, with expected averages of 1 year (for osteoporosis) to 3 months (for other conditions)]: The sensitivity, specificity, positive and negative predictive value of the new test will be compared to expert clinical diagnosis as the gold standard. This diagnosis is established during follow-up and based on clinical observations, BMD results, bone turnover markers and response to treatments.
Area under the receiver-operator curve (AUROC) of calcium δ44/40 Ca (‰) values compared to bone turnover markers, with expert clinical diagnosis as the golden standard [follow-up will vary on clinical basis, with expected averages of 1 year (for osteoporosis) to 3 months (for other conditions)]: Osteocalcin and bèta-CTx (C-terminal telopeptide of type I collagen) will be measured.

Other outcomes

Inter- and intra-assay variability of plasma and urine calcium δ44/40 Ca (‰) values [follow-up will vary on clinical basis, with expected averages of 1 year (for osteoporosis) to 3 months (for other conditions)]
calcium δ44/40 Ca (‰) values of human bone samples [before and 1 year after kidney transplantation]: Secondary use of bone biopsy samples obtained in the Leuven Bone Biopsy Program (NCT01886950)

+Eligibility

Sex: All, ages: 18 Years to any, accepts healthy volunteers

Inclusion Criteria:

* DXA (dual energy X-ray absorptiometry) T-score known clinically to be = or < -2.5 OR presence of low-energy osteoporotic fractures (i.e. excluding those of the skull, fingers and toes) \[for osteoporosis and calcium malabsorption patients\]

Exclusion Criteria:

* inability to provide written informed consent

+Locations (2)

Facility	City	Country	Status
UZ Leuven	Leuven	Belgium
GEOMAR-Helmholtz Centre for Ocean Research	Kiel	Germany

+Publications

Khalil R, Antonio L, Laurent MR, David K, Kim NR, Evenepoel P, Eisenhauer A, Heuser A, Cavalier E, Khosla S, Claessens F, Vanderschueren D, Decallonne B. Early effects of androgen deprivation on bone and mineral homeostasis in adult men: a prospective cohort study. Eur J Endocrinol. 2020 Aug;183(2):181-189. doi: 10.1530/EJE-20-0348. PMID 32454455

+Investigators

Dirk Vanderschueren, MD, PhD, Principal investigator, UZ Leuven

My Notes

Public

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