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

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

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.

Study Overview

• Status: Completed
• Conditions: Bone Diseases; Osteoporosis; Osteomalacia

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.

• Study Type: Observational
• Enrollment (Actual): 54

Contacts and Locations

Study Locations

• Belgium
  • Leuven, Belgium, 3000
    • UZ Leuven
• Germany
  • Kiel, Germany, 24148
    • GEOMAR-Helmholtz Centre for Ocean Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Tertiary care clinical convenience sample Healthy volunteers recruited from the communities in Leuven and neighbouring cities Siblings, parents or other relatives of patients

Description

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

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Control
• Time Perspectives: Prospective

Number of groups / cohorts

4

Cohorts and Interventions

Group / Cohort
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

What is the study measuring?

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)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	Secondary use of bone biopsy samples obtained in the Leuven Bone Biopsy Program (NCT01886950)	before and 1 year after kidney transplantation

Collaborators and Investigators

• Sponsor: Universitaire Ziekenhuizen KU Leuven
• Collaborators: GEOMAR-Helmholtz Centre for Ocean Research
• Investigators: Principal Investigator: Dirk Vanderschueren, MD, PhD, UZ Leuven

Publications and helpful links

General 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.

Study record dates

Study Major Dates

• Study Start: October 1, 2014
• Primary Completion (Actual): December 1, 2018
• Study Completion (Actual): December 1, 2018

Study Registration Dates

• First Submitted: September 22, 2014
• First Submitted That Met QC Criteria: September 25, 2014
• First Posted (Estimate): September 30, 2014

Study Record Updates

• Last Update Posted (Actual): November 6, 2020
• Last Update Submitted That Met QC Criteria: November 4, 2020
• Last Verified: October 1, 2020

More Information

Terms related to this study

• Keywords: Bone Turnover Markers; Calcium Isotopes
• Additional Relevant MeSH Terms: Metabolic Diseases; Nutrition Disorders; Musculoskeletal Diseases; Avitaminosis; Deficiency Diseases; Malnutrition; Bone Diseases, Metabolic; Calcium Metabolism Disorders; Rickets; Vitamin D Deficiency; Osteoporosis; Bone Diseases; Osteomalacia
• Other Study ID Numbers: UZ Leuven - s56719

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No