PTH And Calcium Responses to Exercise in Older Adults Experiment 2 (PACE Sr. 2)

Study Overview
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Brief Summary
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Declines in serum calcium during exercise may cause increases in markers of bone resorption. This study will determine if preventing the decline serum ionized calcium experienced at the onset of exercise through the use of a calcium clamp also prevents increases in blood biomarkers associated with bone resorption.

Detailed Description
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Participants will undergo two identical walking exercise sessions on a treadmill. One session will occur until continuous calcium infusion and the other will be under continuous saline infusion. C-telopeptide, parathyroid hormone, total calcium, and serum ionized calcium will be monitored to distinguish differences in bone activity under the two conditions.

Official Title
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PTH And Calcium Responses to Exercise in Older Adults Experiment 2 (PACE Sr. 2)

Conditions
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Osteoporosis

Intervention / Treatment
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* Drug: Calcium Chloride/Calcium Gluconate
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy adults aged 60-80 y Currently taking a bisphosphonate medication Exclusion Criteria: Use of medications (other than bisphosphonates) in the past 6 months known to affect bone metabolism (e.g., thiazide diuretics, oral glucocorticoids) Bone Mineral Density (BMD) t score < -3.0 at the total hip or lumbar spine Known disease or condition associated with intestinal malabsorption Moderate or severe renal impairment defined as an estimated glomerular filtration rate of <60 mL/min/1.73m2 based on the Modified Diet in Renal Disease (MDRD) equation Chronic hepatobiliary disease, defined as liver function tests (AST, ALT) >1.5 times the upper limit of normal; if such values are obtained on initial screening and thought to be transient in nature, repeated testing will be allowed Thyroid dysfunction, defined as an ultrasensitive TSH <0.5 or >5.0 mU/L; volunteers with abnormal TSH values will be re-considered for participation in the study after follow-up evaluation by the PCP with initiation or adjustment of thyroid hormone replacement Serum calcium <8.5 or >10.3 mg/dL Serum 25(OH)D <20 ng/mL; volunteers with abnormal serum 25(OH)D values may be re-considered for participation in the study if serum 25(OH)D is >20 ng/mL after vitamin D supplementation Uncontrolled hypertension defined as resting systolic BP >150 mmHg or diastolic BP>90 mmHg; participants who do not meet these criteria at first screening will be re-evaluated, including after follow-up evaluation by the PCP with initiation or adjustment of anti-hypertensive medications History of type 1 or type 2 diabetes Cardiovascular disease; subjective or objective indicators of ischemic heart disease (e.g., angina, ST segment depression) or serious arrhythmias at rest or during the graded exercise test (GXT) without follow-up evaluation will be cause for exclusion; follow-up evaluation must include diagnostic testing (e.g., stress echocardiogram or thallium stress test) with interpretation by a cardiologist Diagnosis or history of asthma

Ages Eligible for Study
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Minimum Age: 60 Years
Maximum Age: 80 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: Prevention
Allocation: Non-Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Calcium Infusion<br>Continuous calcium infusion during exercise | Drug: Calcium Chloride/Calcium Gluconate<br>* Calcium (as either calcium chloride or calcium gluconate in half normal saline) will be delivered via IV during exercise to keep serum ionized calcium levels above baseline. The clamp is modeled after the hyperglycemic glucose clamp.<br>|
| Placebo Comparator: Saline Infusion<br>Continuous saline infusion during exercise | Drug: Placebo<br>* Saline Infusion<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Parathyroid Hormone (PTH) | PTH will be measured during baseline, throughout exercise, and during recovery at regular intervals. The investigators are looking to see how PTH changes over the course of the exercise and recovery period in both the calcium and saline. The investigators anticipate that PTH will be higher in the saline condition versus the calcium. The investigators expect that men and women will respond similarly. | At baseline, through 60 minutes of exercise, and during 4 hours of recovery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in C-telopeptide (CTX) | CTX will be measured during baseline, throughout exercise, and during recovery at regular intervals. The investigators are looking to see how PTH changes over the course of the exercise and recovery period in both the calcium and saline. The investigators anticipate that CTX will be higher in the saline condition versus the calcium. The investigators expect that men and women will respond similarly. | At baseline, through 60 minutes of exercise, and during 4 hours of recovery | 
| Change in Total Calcium (Ca) | Total Ca will be measured during baseline, throughout exercise, and during recovery at regular intervals. The investigators are looking to see how Ca changes over the course of the exercise and recovery period in both the calcium and saline conditions. | At baseline, through 60 minutes of exercise, and during 4 hours of recovery |