Exercise Mode and Bone

Study Overview
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Brief Summary
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Endurance exercise is often recommended to improve cardiometabolic health and maintain bone health throughout life and to prevent osteoporotic fracture. However, there is evidence to suggest that bone does not always adapt in the way that is expected, and that endurance exercise may lead to bone loss under certain conditions. Disruptions in calcium homeostasis during exercise may explain this observation, and preliminary data suggests that the mode of exercise (i.e., cycling versus treadmill) may result in different magnitudes of change in bone biomarkers. The purpose of this study is to determine if mode of exercise results in a differential bone biomarker response to an acute exercise bout in older Veterans. Blood samples will be collected before, during, and after 2 acute exercise bouts: 1) brisk treadmill walking; and 2) vigorous stationary cycling. Bouts will be matched for relative intensity and duration. This data will be used to develop future exercise interventions in older Veterans aimed at preserving both cardiometabolic and bone health.

Detailed Description
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Endurance exercise is frequently recommended as a means to reduce the risk of cardiometabolic diseases and to reduce the risk of osteoporotic fracture. However, bone does not always adapt in the way that would be expected, and there is evidence that endurance exercise may lead to bone loss under certain conditions. It is the investigators contention that disruptions in calcium homeostasis during exercise, resulting in decreases in serum ionized calcium (iCa) and increases in parathyroid hormone (PTH) and c-telopeptide of type I collagen (CTX; a marker of bone resorption) at the onset of exercise, may be responsible for the lack of improvements in bone mineral density that are anticipated. Acute studies in this area have predominantly focused on young, healthy adults, primarily men, during stationary cycling exercise. Few studies have been conducted in older adults, but those studies have found that older adults experience similar disruptions in calcium homeostasis in response to an acute bout of endurance exercise. Preliminary comparisons of the investigators studies, as well as research from other labs, also suggests that that mode of exercise conducted during these acute exercise bouts may be an important determining factor in the catabolic bone response to exercise. It appears that weight-bearing exercise (i.e., treadmill) results in smaller increases in PTH and CTX compared to weight-supported exercise (i.e., stationary cycling). This has never been tested using a within-subjects design, so it is unclear if these observed differences are due to the mode of exercise, lab-to-lab differences, or other underlying factors. To address this gap in knowledge, 30 Veterans (15 men, 15 women), aged 60+ years, will complete two 1-hour acute exercise bouts: 1) brisk treadmill walking at 70-80% of maximal heart rate; 2) vigorous stationary cycling at 70-80% maximal heart rate. Blood samples will be collected to measure iCa, PTH, CTX and procollagen type I n-terminal propeptide (P1NP) before, during, and after each exercise bout. The order of the exercise bouts will be randomized and counter-balanced. The primary aim is to determine if mode of exercise results in a differential bone biomarker response in older Veterans. This information is essential for understanding how future exercise interventions should be designed to benefit both cardiometabolic health and bone health. This is especially relevant to Veteran health due to the high burden of both cardiometabolic diseases (e.g., diabetes, heart disease) in the population, as well as evidence of increased osteoporotic fracture risk. The proposed research is significant because it is addressing a knowledge gap that has prevented the ability to design exercise and lifestyle interventions aimed at preserving multiple components of Veteran health, which could have a lasting impact on Veteran quality of life and functional independence. The proposed research is innovative because it is testing a novel hypothesis, the mode of exercise on disruptions in calcium homeostasis, in a population that could greatly benefit from the knowledge to be gained. While the proposed research is an acute study, the results generated will be used to design future clinical interventions for Veteran health. Long-term, information gained from this research will help to define the optimal exercise prescription to improve cardiometabolic without compromising bone health aging Veterans.

Official Title
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Comparison of Exercise Mode on Disruptions in Calcium Homeostasis

Conditions
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Osteoporosis, Aging

Intervention / Treatment
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* Behavioral: Exercise Mode


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy older (60+ y) Veteran women and men will be eligible to participate All volunteers must be accustomed to performing 60 minutes of vigorous cycling and treadmill exercise Exclusion Criteria: impaired renal function, defined as an eGRF of <60 mL/min/1.73m2;(Florkowski and Chew-Harris 2011) hepatobiliary disease, defined as liver function tests (AST, ALT) >1.5 times the upper limit of normal thyroid dysfunction, defined as an ultrasensitive thyroid stimulating hormone (TSH) <0.5 or >5.0 mU/L serum Ca <8.5 or >10.3 mg/dL; 5) serum 25(OH)D <20 ng/mL uncontrolled hypertension, defined as resting systolic blood pressure (BP) >150 mmHg or diastolic BP >90 mmHg history of type 1 or type 2 diabetes cardiovascular disease; defined as 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) volunteers who have a positive GXT can be re-considered after follow-up evaluation, which must include diagnostic testing (e.g., stress echocardiogram or thallium stress test) with interpretation by a cardiologist anemia, defined as a serum hemoglobin <12.1 g/dL for women and <14.3 g/dL for men fracture in the past 6 months current diagnosis or symptoms of COVID-19 In the event of abnormal BP, live function, TSH, 25(OH)D, or hemoglobin values, volunteers can be reassessed, including after appropriate follow-up evaluation and treatment by a primary care provider Those who have experienced symptoms of COVID-19 or have been formally diagnosed will be allowed to participate once symptoms have resolved and they are approved to return to exercise by their primary care provider

Ages Eligible for Study
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Minimum Age: 60 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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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: Crossover design comparing mode of endurance exercise (cycling versus treadmill).
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Stationary Cycling<br>All participants will complete one, 60-minute bout of stationary cycling | Behavioral: Exercise Mode<br>* Stationary cycling or treadmill walking<br>|
| Experimental: Treadmill Walking<br>All participants will complete one, 60-minute bout of treadmill walking | Behavioral: Exercise Mode<br>* Stationary cycling or treadmill walking<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| c-telopeptide of type I collagen (CTX) change | CTX is a blood marker of bone resorption. Reference range is 0.1-0.8 ng/mL with lower concentrations suggesting less bone resorption. | Before to up to 48 hours after acute exercise bout | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| procollagen of type I n-terminal propeptide (P1NP) change | PINP is a blood marker of bone formation. Reference range is 19-80 ng/mL with lower concentrations suggesting less bone formation. | Before to up to 48 hours after acute exercise bout | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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exercise, bone resorption, calcium