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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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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

Conditions
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Bone Diseases, Osteomalacia, Osteoporosis

Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Osteoporosis<br>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<br>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<br>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<br>N=40 Men and women ≤ 40 years recruited from the population | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Likelihood ratio (LR) of urinary calcium δ44/40 Ca (‰) values for diagnosing negative skeletal calcium balance | 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. | follow-up will vary on clinical basis, with expected averages of 1 year (for osteoporosis) to 3 months (for other conditions) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Likelihood ratio (LR) of plasma calcium δ44/40 Ca (‰) values for diagnosing negative skeletal calcium balance | 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. | follow-up will vary on clinical basis, with expected averages of 1 year (for osteoporosis) to 3 months (for other conditions) | 
| 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 | Osteocalcin and bèta-CTx (C-terminal telopeptide of type I collagen) will be measured. | follow-up will vary on clinical basis, with expected averages of 1 year (for osteoporosis) to 3 months (for other conditions) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Bone Turnover Markers, Calcium Isotopes