ClinicalTrials.gg
CompletedNCT04815824Updated Jul 20, 2025Results posted

Exercise Mode and Acute Bone Resorption

An interventional study of Exercise Mode in Osteoporosis and Aging, sponsored by VA Office of Research and Development. Completed at 1 site in United States. Open to participants aged 60 Years and older, including healthy volunteers. Per ClinicalTrials.gov, last updated 2025-07-20.

Sponsored by VA Office of Research and Development · Not applicable, Interventional, and Prevention

Phase
Not applicable
Study type
Interventional
Enrollment
9
Allocation
Randomized
Ages
60 Years and older
Sex
All
01

Study summary

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.

Read the detailed description

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.

02

Conditions studied

  • Osteoporosis
  • Aging

Keywords

  • exercise
  • bone resorption
  • calcium
03

In context

Osteoporosis

1,601 studies on the registry are indexed under Osteoporosis; 209 are open to participants now.

This study's enrollment of 9 is below the median of 88 across 1,084 interventional studies indexed under Osteoporosis.

Browse Osteoporosis studies →

Lead sponsor

VA Office of Research and Development is the lead sponsor of 1,771 studies on the registry; 392 are open to participants now.

Of its 213 completed or terminated interventional studies of FDA-regulated products, 185 (87%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
60 Years and older
Sexes eligible
All
Accepts healthy volunteers
Yes

Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.

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

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 (, ALT) >1.5 times the
  • 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 \<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
Terms in these criteria, in plain language(3)

Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.

ALT and AST (liver enzymes)

Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.

Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.

ULN (upper limit of normal)

The top of the normal range for a blood test, as set by the laboratory that runs it. Each lab prints its own range next to your result.

“≤ 2.5 × ULN” means the result can be up to two and a half times that top value.

Hemoglobin (Hb)

The protein in red blood cells that carries oxygen. A low level is anaemia, which can cause tiredness and breathlessness. Measured in g/dL or g/L (9 g/dL is 90 g/L).

05

Study design

Phase
Not applicable
Primary purpose
Prevention
Allocation
Randomized
Intervention model
Crossover assignment
Masking
None (open label)
Enrollment
9 participants (actual)

Study arms

  • Experimental
    Stationary Cycling

    All participants will complete one, 60-minute bout of stationary cycling

    Behavioral: Exercise Mode

  • Experimental
    Treadmill Walking

    All participants will complete one, 60-minute bout of treadmill walking

    Behavioral: Exercise Mode

Interventions

  • BehavioralExercise Mode

    Stationary cycling or treadmill walking

06

What researchers measure

Primary outcomes

  1. 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.

    Time frame: Before to up to 48 hours after acute exercise bout

Secondary outcomes

  1. 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.

    Time frame: Before to up to 48 hours after acute exercise bout

07

Results

Posted Jul 20, 2025

Participant flow

First Intervention (60 Minutes)
Participant flow — First Intervention (60 Minutes)
MilestoneStationary Cycling First, Then Treadmill WalkingTreadmill Walking First, Then Stationary Cycling
Started54
Completed54
Not completed00
Washout (1 Week)
Participant flow — Washout (1 Week)
MilestoneStationary Cycling First, Then Treadmill WalkingTreadmill Walking First, Then Stationary Cycling
Started54
Completed54
Not completed00
Second Intervention (60 Minutes)
Participant flow — Second Intervention (60 Minutes)
MilestoneStationary Cycling First, Then Treadmill WalkingTreadmill Walking First, Then Stationary Cycling
Started54
Completed54
Not completed00

Outcome measures

PrimaryC-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.

Time frame:
Before to up to 48 hours after acute exercise bout
Reported as:
Mean · ng/mL
C-telopeptide of Type I Collagen (CTX) Change
ng/mLStationary CyclingTreadmill Walking
C-telopeptide of Type I Collagen (CTX) Change0.09 ± 0.060.08 ± 0.07
SecondaryProcollagen 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.

Time frame:
Before to up to 48 hours after acute exercise bout
Reported as:
Mean · ng/mL
Procollagen of Type I N-terminal Propeptide (P1NP) Change
ng/mLStationary CyclingTreadmill Walking
Procollagen of Type I N-terminal Propeptide (P1NP) Change-3.1 ± 7.8-1.5 ± 7.1

Adverse events

Collected over Adverse event information was collection from time of informed consent to completion of the study, which was approximately 8 weeks.. Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Stationary Cycling0/9 (0%)0/9 (0%)0/9 (0%)
Treadmill Walking0/9 (0%)0/9 (0%)0/9 (0%)

Baseline characteristics

Because all participants completed both interventions (60 minutes of stationary cycling, 60 minutes of treadmill walking), participant characteristics have been collapsed into one Arm/Group titled "All Study Participants."

Age, Categorical
Age, Categorical(Participants)All Study Participants
<=18 years0
Between 18 and 65 years0
>=65 years9
Age, Continuous
Age, Continuous(years)All Study Participants
Mean72 ± 2
Sex: Female, Male
Sex: Female, Male(Participants)All Study Participants
Female1
Male8
Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)All Study Participants
Hispanic or Latino2
Not Hispanic or Latino7
Unknown or Not Reported0
Race (NIH/OMB)
Race (NIH/OMB)(Participants)All Study Participants
American Indian or Alaska Native0
Asian0
Native Hawaiian or Other Pacific Islander0
Black or African American0
White8
More than one race1
Unknown or Not Reported0
Region of Enrollment
Region of Enrollment(Participants)All Study Participants
United States5
Cardiorespiratory Fitness (VO2peak)
Cardiorespiratory Fitness (VO2peak)(mL/kg/min)All Study Participants
Mean25.8 ± 3.5
08

Study locations

1 site
  • Rocky Mountain Regional VA Medical Center, Aurora, CO
    Aurora, Colorado 80045-7211, United States
09

References and documents

Study documents

PDFs hosted by the registry, ClinicalTrials.gov.

Individual participant data

Plan to share: No

10

Timeline

Tracking since Sep 25, 2026
ElapsedEstimatedEstimated, not yet reachedSimilar studies: half by the dot; the band is the middle halfHalf of similar studies reached it by the dot; the band is the middle half, from a quarter to three quarters

Ran from Oct 2021 to primary completion in Jun 2024, 32 months.

Results were first posted in Jul 2025, 1 year after primary completion.

Of 219 non-industry interventional studies with no phase under Osteoporosis, half reached primary completion within 22 months of starting (the median), counting those still running; a quarter within 8 and three quarters within 49. This study's 32 months is above that.

Counting every sponsor, half of 238 studies reached it within 26 months; a quarter within 9 and three quarters within 50.

How these figures are worked out, and which studies are left out of them.

Registered
Mar 22, 2021
First posted
Mar 25, 2021
StartActual
Oct 8, 2021
Primary completionActual
Jun 30, 2024
CompletionActual
Sep 30, 2024
Results first posted
Jul 20, 2025
Last update
Jul 20, 2025
What these dates mean
Start.
When the first participant enrolled; while estimated, when the study expects to open to recruitment.
Primary completion.
When the last participant was examined or treated to collect data for the study's main question, its primary outcome. A study that stopped early gives the date its data collection stopped.
Completion.
When the last participant's last visit took place, for every outcome, secondary ones and side effects included: the end of the study. Often later than primary completion, sometimes the same day.
Actual and Est.
Actual means the registry says the date has happened. Est. (estimated) is a date the sponsor plans or expects. It can still move, and the sponsor is expected to change it to actual once it has passed.
No changes since tracking began. The registry record was last updated on Jul 20, 2025, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT04815824
Responsible party
Sponsor
First posted
Mar 25, 2021
Start date
Oct 8, 2021
Primary completion
Jun 30, 2024
Completion
Sep 30, 2024
Results posted
Jul 20, 2025
Last update
Jul 20, 2025

Study contacts

Sarah J Wherry, PhD
principal investigator · Rocky Mountain Regional VA Medical Center, Aurora, CO

Oversight

Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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This study is completed, as verified in Jul 2025. You cannot join it, but the record below documents what was studied.

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