Osteoporosis
Conditions
Brief summary
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
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.
Interventions
DRUGCalcium Chloride/Calcium Gluconate
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.
This is the placebo comparative infusion. Half-normal saline will be infused at the second collection visit following the identical infusion schedule determined during the calcium infusion visit.
Sponsors
National Center for Advancing Translational Sciences (NCATS)
University of Colorado, Denver
Study design
Allocation
NON_RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
60 Years to 80 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Parathyroid Hormone (PTH) | baseline, 60 minutes | Change in PTH will be measured from baseline to end of exercise |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in C-telopeptide (CTX) | baseline, 60 minutes | Change in CTX will be measured from baseline to the end of 60 minutes of exercise |
| Change in Ionized Calcium | baseline, 60 minutes | Change in ionized calcium will be measured from baseline to the end of 60 minutes of exercise |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Calcium Infusion Continuous calcium infusion during exercise | 12 |
| Total | 12 |
Baseline characteristics
| Characteristic | Calcium Infusion |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 12 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants |
| Age, Continuous | 65.5 years STANDARD_DEVIATION 5.7 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 10 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 10 Participants |
| Region of Enrollment United States | 12 participants |
| Sex: Female, Male Female | 6 Participants |
| Sex: Female, Male Male | 6 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 12 | 0 / 12 |
| other Total, other adverse events | 0 / 12 | 0 / 12 |
| serious Total, serious adverse events | 0 / 12 | 0 / 12 |
Outcome results
Primary
Change in Parathyroid Hormone (PTH)
Change in PTH will be measured from baseline to end of exercise
Time frame: baseline, 60 minutes
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Calcium Infusion | Change in Parathyroid Hormone (PTH) | 8.5 pg/mL |
| Saline Infusion | Change in Parathyroid Hormone (PTH) | 20.0 pg/mL |
Secondary
Change in C-telopeptide (CTX)
Change in CTX will be measured from baseline to the end of 60 minutes of exercise
Time frame: baseline, 60 minutes
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Calcium Infusion | Change in C-telopeptide (CTX) | 0.01 ng/mL |
| Saline Infusion | Change in C-telopeptide (CTX) | 0.11 ng/mL |
Secondary
Change in Ionized Calcium
Change in ionized calcium will be measured from baseline to the end of 60 minutes of exercise
Time frame: baseline, 60 minutes
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Calcium Infusion | Change in Ionized Calcium | 0.07 mg/dL |
| Saline Infusion | Change in Ionized Calcium | -0.15 mg/dL |