Comparison of Calcium Metabolism in Caucasian and Asian Postmenopausal Women of Chinese Descent and the Use of Strontium as a Qualitative Marker of Calcium Metabolism

Study Overview
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Brief Summary
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This study aims to: 1) quantitatively assess parameters of bone calcium balance in healthy postmenopausal Asian women of Chinese descent; 2) assess possible ethnic differences in calcium metabolism by direct comparison of acquired data in Chinese postmenopausal women with those acquired earlier in Caucasian postmenopausal women using the same methodology; 3) assess differences in calcium and strontium metabolism in parallel to evaluate if strontium stable isotopes can be used for tracing bone calcium metabolism qualitatively

Detailed Description
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The study will follow closely the protocol that was used previously by the PI at ETH Zurich to study calcium metabolism in healthy postmenopausal women. Calcium metabolism will be studied after a single oral administration of a calcium tracer (Ca-41) and by following the excretion of the tracer in urine over 6 months. Obtained data will be used to assess parameters of calcium metabolism (flux rates and sizes of body calcium compartments) by kinetic modelling. A strontium tracer (Sr-84) will be administered in parallel and its urinary excretion pattern compared to Ca-41 excretion to determine if strontium tracers can be used to assess calcium metabolism qualitatively. Subjects will be supplemented with Vit D throughout the study. Vit D supplementation will commence 1 month before isotope administration.

Official Title
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A Comparative Study of Calcium Metabolism in Caucasian and Asian Postmenopausal Women of Chinese Descent and the Use of Strontium as a Qualitative Marker of Calcium Metabolism in Humans

Conditions
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Calcium Metabolism

Intervention / Treatment
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* Other: Ca-41(isotope tracer)
* Other: Sr-84 (isotope tracer)
* Dietary Supplement: Vitamin D


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Last menstrual bleeding was at least 5 years ago. Between the ages of 50 and 75 years old. Both parents and 4 grandparents are/were of Chinese descent. It is not a necessity for the participant, participant's parents and grandparent's to be born and raised in Singapore to participate in this study. BMI above 16 and below 30 Exclusion Criteria: Diagnosed with osteoporosis Presence of significant liver disease, malignancy (excluding myeloma in the study group), malabsorption syndrome, hypoparathyroidism, hyperparathyroidism, sarcoidosis or hyperthyroidism (from toxic multinodular goitre or Graves disease), Paget's disease osteosarcoma, acromegaly, Cushing's syndrome, hypopituitarism, diabetes mellitus or severe chronic obstructive pulmonary disease. Current smoking and an alcohol intake exceeding one standard drink per day Undergoing treatment with any of the following drugs (within the last 12 months) i) adrenocorticoid steroids (3 months or longer at anytime or >10 days of treatment within the previous 12 months) ii) anticonvulsant therapy iii) pharmacological doses of thyroid hormone (causing decline of TSH below normal) iv) bisphosphonates v) calcitonin vi) synthetic parathyroid hormone vii) selective estrogen receptor modulators viii) strontium ranelate ix) estrogen therapy x ) chemotherapeutic agents xi) sodium fluoride (any history of treatment with fluoride) xii) medications known to affect calcium metabolism (diuretics, antacids, calcium channel blockers etc.). Presence of any other chronic illnesses. Any other significant medical, psychiatric and/or social issue as determined by the investigator that would compromise subject's safety and/or compliance with trial procedure. Any other clinically significant screening laboratory abnormality (as determined by the investigators).

Ages Eligible for Study
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Minimum Age: 50 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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Female

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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Design Details

Primary Purpose: Basic Science
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Ca-41 & Sr-84 (isotope tracers) & vit D<br>Dosages: 3.7 kBq (100 nCi) Ca-41, 5 mg of Sr-84 and 400IU of vitamin D (daily) | Other: Ca-41(isotope tracer)<br>* Ca-41 is given orally in the form of (Ca-41)Cl3 in citrate-buffered solution. Tracer will be used to determine parameters of calcium metabolism based on tracer excretion data.<br>Other: Sr-84 (isotope tracer)<br>* Sr-84 is given orally in the form of (Sr-84)Cl2 in aqueous solution.Tracer will be used to determine parameters of strontium metabolism based on tracer excretion data.<br>Dietary Supplement: Vitamin D<br>* One tablet daily (400IU per tablet)<br>* Other names: Cholecalciferol;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time changes in urinary tracer excretion (Ca-41 and Sr-84) | Urine samples collected from participants are analysed for calcium and strontium content as well as Ca-41 and Sr-84 excretion. | 6 months post dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Flux rates and relative compartment sizes (mineralized bone, exchangeable bone calcium, plasma calcium) of the study population | Flux rates (mg/day) and calcium distribution between compartments (% body calcium) will be obtained by compartmental modelling of urinary tracer data. Obtained data will be compared to a mirroring study conducted earlier in Caucasian postmenopausal women. | 6 months post dose | 
| Comparison between flux rates and relative compartment sizes for calcium and strontium in each individual subject | Flux rates (mg/day), and calcium and strontium distribution between compartments (% body calcium and strontium ) will be obtained by compartmental modelling of urinary tracer data | 6 months post dose | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Calcium metabolism, Osteoporosis, Postmenopausal women