An interventional study of Endurance exercise intervention in Exercise, Bone Resorption and Bone Formation, sponsored by VA Office of Research and Development. Completed at 1 site in United States. Open to participants aged 25 Years to 75 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2026-04-06.
Sponsored by VA Office of Research and Development · Not applicable, Interventional, and Other
Exercise is essential for building and maintaining bone mass and strength, but current exercise recommendations for how to achieve this lack detail on the optimal exercise prescription. Recent studies found that blood calcium level decreases during exercise, and that calcium is mobilized from bone to slow the decline. If this occurs repeatedly during exercise training, it could diminish the potential benefits of exercise to improve bone health. The proposed study will determine whether further research on pre-exercise supplemental calcium to minimize the decline in blood calcium level during exercise is warranted. This research is important for Veterans because they are at increased risk of hip fracture when compared with non-Veterans. Further, because osteoporosis in men is under-recognized and under-treated, providing male (and female) Veterans with more specific exercise and nutrition guidelines has the potential to enhance bone health, reduce fracture risk, and improve quality of life.
Exercise is essential for building and maintaining bone mass and strength, but recent work has raised the possibility that current exercise recommendations for bone health may not be appropriate. There is strong evidence that a single bout of vigorous exercise has an acute catabolic effect in bone (i.e., increased resorption) that lasts several hours. This is mediated by a decrease in serum calcium (Ca) during exercise, which stimulates parathyroid hormone (PTH) secretion. PTH then activates bone resorption to mobilize Ca from bone, presumably to prevent the decrease in serum Ca from progressing to a harmful level. This cascade of events can be markedly attenuated by minimizing the decline in serum Ca during exercise via either intravenous or oral Ca administration. The timing of Ca supplementation relative to exercise is likely important, because it must be available for gut absorption during exercise. Interestingly, repeated pharmacologic stimulation of the PTH receptor with PTH analogs (teriparatide, abaloparatide) has anabolic effects on bone, suggesting that repeated exercise-induced increases in PTH could have a chronic anabolic skeletal effect, in addition to the acute catabolic effect, which may be apparent only after repeated exercise sessions. If this is the case, suppressing the PTH response with pre-exercise Ca supplementation may not be appropriate. In this context, this proof-of-concept study will include a short exercise intervention consisting of treadmill exercise at 70% to 80% of maximal heart rate, 60 minutes per day, 4 days per week, for 4 weeks. Serum markers of bone formation and resorption will be measured before, during, and for 24 hours after the 1st, 8th, and 16th exercise sessions to address two questions: 1) Does the acute catabolic response of bone to a single bout of exercise continue to occur with repeated exercise sessions (i.e., exercise training)? 2) Does exercise training also generate an anabolic PTH-mediated bone response, similar to the anabolic response to PTH analog therapy? If the answers to questions 1 and 2 are YES (persistent catabolic signal) and NO (lack of anabolic signal), this will support the need for the randomized controlled trial (RCT), which will evaluate whether taking Ca before exercise to attenuate the acute catabolic response improves skeletal adaptations to exercise training. The overarching goal is to improve the currently imprecise recommendations for exercise to improve and maintain bone health. This research is of high relevance to Veterans, who are at increased risk of hip fracture when compared with non-Veterans. Further, because osteoporosis in men is under-recognized, under-diagnosed, and under-treated, providing male Veterans with an effective non-pharmacologic therapeutic option to reduce fracture risk may help close this treatment gap. The potential impact of this research also extends beyond Veterans. It could lead to reduced risk of exercise-related bone injury (i.e., stress fractures) in active duty military personnel and athletes and to improved bone health in the general population.
167 studies on the registry are indexed under Bone Resorption; 28 are open to participants now.
This study's enrollment of 18 is below the median of 24 across 146 interventional studies indexed under Bone Resorption.
Browse Bone Resorption studies →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.
Compared within Bone Resorption, this study's primary condition as ClinicalTrials.gg classifies it; the registry's first condition term is Motor Activity. The counts are of registry records indexed under each term, refreshed daily. How we classify →
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.
Female and male Veterans aged 25 to 45 y and 55 to 75 y will be enrolled. Eligible volunteers will be normally active (e.g., recreational cycling or walking) but will not participate in regular moderate-to-vigorous exercise. Women will be premenopausal with regular menstrual cycles or , defined as absence of menses for at least 12 mo or, in those who underwent a hysterectomy, a serum follicle stimulating hormone (FSH) >30 mIU/mL.
Exclusion Criteria:
Initiation or change in dose in the past 6 months of medications that affect bone metabolism
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)
>39 kg/m2
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.
Periods have stopped for good: usually no period for 12 months in a row without another medical reason, sometimes confirmed by a blood test (FSH).
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
GFR (glomerular filtration rate) is how much blood the kidneys filter each minute. It is usually estimated from a blood test — eGFR, by formulas such as CKD-EPI or MDRD — and some studies ask for it to be measured directly instead. Usually given in mL/min/1.73 m².
Check the method, the units and the minimum the study states. A value of 90 or above is in the normal-or-high range, but kidney damage can show in other tests too.
A blood test of average blood sugar over the past two to three months, given as a percentage or in mmol/mol. 6.5% (48 mmol/mol) or more is the usual threshold for diabetes, normally confirmed by a second test.
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).
Weight in kilograms divided by height in metres squared. Example: 70 kg and 1.75 m gives 70 ÷ (1.75 × 1.75) ≈ 22.9.
What counts as overweight or obesity differs between countries (some use lower cut-offs), so go by the range the study states.
Postmenopausal
Periods have stopped for good: usually no period for 12 months in a row without another medical reason, sometimes confirmed by a blood test (FSH).
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Corticosteroids (steroids)
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
GFR and eGFR (kidney filtering)
GFR (glomerular filtration rate) is how much blood the kidneys filter each minute. It is usually estimated from a blood test — eGFR, by formulas such as CKD-EPI or MDRD — and some studies ask for it to be measured directly instead. Usually given in mL/min/1.73 m².
Check the method, the units and the minimum the study states. A value of 90 or above is in the normal-or-high range, but kidney damage can show in other tests too.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
HbA1c
A blood test of average blood sugar over the past two to three months, given as a percentage or in mmol/mol. 6.5% (48 mmol/mol) or more is the usual threshold for diabetes, normally confirmed by a second test.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
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).
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
BMI (body mass index)
Weight in kilograms divided by height in metres squared. Example: 70 kg and 1.75 m gives 70 ÷ (1.75 × 1.75) ≈ 22.9.
What counts as overweight or obesity differs between countries (some use lower cut-offs), so go by the range the study states.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
All participants engage in exercise training
Behavioral: Endurance exercise intervention
All participants engage in treadmill walking 4 days/week, 60 minutes/day, at 70-80% of HRmax for 4 weeks.
Change in C-terminal Peptide of Type 1 Collagen (CTX)
CTX is a marker of bone resorption. An increase in CTX in response to exercise is evidence of an acute catabolic response of bone.
Time frame: The primary outcome for Aim 1 is the change in CTX from immediately before exercise to 60 minutes after exercise during the 1st, 8th, and 16th exercise bout. Results are for each exercise bout and for the average of all the bouts combined.
Change in Procollagen 1 Intact N-terminal Propeptide (P1NP)
P1NP is a marker of bone formation. An increase in P1NP from before to after an exercise intervention is evidence of an anabolic response of bone.
Time frame: The primary outcome for Aim 2 is the change in the pre-exercise P1NP (15 minutes before exercise) between the 1st and the 16th exercise bout (comparison of 2 time points).
Change in P1NP During Exercise
Serum P1NP is measured to determine if there is an acute anabolic response of bone to exercise and whether it changes in response to exercise training
Time frame: Change in serum P1NP is measured from before to immediately after the 60 minutes of exercise during the 1st, 8th, and 16th exercise bout. The average change across all exercise bouts is also included.
Urinary Calcium Excretion (uCa)
Urinary tCa is used to account for Ca loss subsequent to the activation of bone resorption during exercise
Time frame: Urinary Ca excretion is measured over the 4 hours of recovery after exercise. Results are presented for the 1st, 8th, and 16th exercise bout individually and for the average excretion across all 3 collections.
Change in Serum Ionized Ca (iCa)
Serum iCa is measured to assess the stimulus for PTH secretion and to describe the pattern of change in iCa during and after exercise
Time frame: Serum iCa is measured before and 15 minutes after the 60 minutes of exercise during the 1st, 8th, and 16th exercise bout. Average change across all three exercise collection bouts is also provided.
Change in Serum Total Ca (tCa)
Serum tCa is measured to help interpret changes in iCa (e.g., changes in Ca binding) and to describe the pattern of change in tCa during and after exercise
Time frame: Change in serum tCa is measured before and 15 minutes after the 60 minute exercise bout during the 1st, 8th, and 16th exercise bouts. Average change across all 3 collection bouts is also included.
Change in Serum Parathyroid Hormone (PTH)
Serum PTH is measured to assess the stimulus for the activation of bone resorption and to describe the pattern of change in PTH during and after exercise
Time frame: Serum PTH is measured before and 15 minutes after the 60 minute exercise bout. Results are presented for the 1st, 8th, and 16th exercise bouts individually and for the average change across all 3 collection bouts.
Change in Serum Phosphorus (PO4)
Serum PO4 is measured because it is a potential stimulus for PTH secretion
Time frame: Serum PO4 is measured before and 15 minutes after the end of the 60 minute exercise bout at the 1st, 8th, and 16th exercise bout. Overall change across all 3 visits is also reported.
Change in Hematocrit (Hct)
Hct is used to adjust iCa, tCa, PTH, CTX, P1NP, and PO4 for the plasma volume contraction that occurs with exercise
Time frame: Hct is measured before and 15 minutes after the 60 minutes of exercise to correct for plasma volume shifts at the 1st, 8th, and 16th exercise bout. Average change across all 3 exercise bouts is also provided.
Change in Hemoglobin (Hgb)
Hgb is used to adjust iCa, tCa, PTH, CTX, P1NP, and PO4 for the plasma volume contraction that occurs with exercise
Time frame: Hgb is measured before and 15 minutes after 60 minutes of exercise to correct for plasma volume shifts. Results are presented for the 1st, 8th, and 16th exercise bouts individually and the average across all 3 exercise collection bouts.
Maximal Heart Rate (HRmax)
HRmax is used to describe the cohort and generate individual exercise prescriptions for the intervention
Time frame: HRmax is measured at only at baseline during the screening maximal treadmill test
Peak Aerobic Power (VO2peak)
VO2peak is used to describe the cardiorespiratory fitness of the participants
Time frame: VO2peak is only measured at baseline during the screening maximal treadmill test as a demographic outcome.
Bone Mineral Density (BMD)
BMD is used to describe the bone health status of the participants
Time frame: BMD of the total hip is measured at baseline
Fat Mass (FM)
FM is used to describe the body composition of participants
Time frame: FM is measured at baseline
Fat-free Mass (FFM)
FFM is used to describe the body composition of participants
Time frame: FFM is measured at baseline
Participants completed an initial in-person screening visit to assess whether inclusion/exclusion criteria were met. Participants were considered "enrolled" once the consent form was signed.
| Milestone | Aerobic Exercise |
|---|---|
| Started | 18 |
| Completed | 8 |
| Not completed | 10 |
| Withdrew: Physician decision | 10 |
| Milestone | Aerobic Exercise |
|---|---|
| Started | 8 |
| Completed | 6 |
| Not completed | 2 |
| Withdrew: Withdrawal by subject | 2 |
CTX is a marker of bone resorption. An increase in CTX in response to exercise is evidence of an acute catabolic response of bone.
| ng/mL | Aerobic Exercise |
|---|---|
| 1st Exercise Bout | 0.03 ± 0.02 |
| 8th Exercise Bout | 0.03 ± 0.04 |
| 16th Exercise Bout | 0.05 ± 0.06 |
| Overall | 0.03 ± 0.08 |
P1NP is a marker of bone formation. An increase in P1NP from before to after an exercise intervention is evidence of an anabolic response of bone.
| ng/mL | Aerobic Exercise |
|---|---|
| Change in Procollagen 1 Intact N-terminal Propeptide (P1NP) | -7.5 ± 15.7 |
Serum P1NP is measured to determine if there is an acute anabolic response of bone to exercise and whether it changes in response to exercise training
| ng/mL | Aerobic Exercise |
|---|---|
| 1st Exercise Bout | 0.0 ± 12.0 |
| 8th Exercise Bout | 9.3 ± 14.0 |
| 16th Exercise Bout | 7.2 ± 7.7 |
| Overall Change | 5.4 ± 11.8 |
Urinary tCa is used to account for Ca loss subsequent to the activation of bone resorption during exercise
| mg | Exercise |
|---|---|
| 1st Exercise Bout | 37.9 ± 57.4 |
| 8th Exercise Bout | 21.5 ± 12.9 |
| 16th Exercise Bout | 22.5 ± 19.4 |
| Overall | 27.5 ± 32.8 |
Serum iCa is measured to assess the stimulus for PTH secretion and to describe the pattern of change in iCa during and after exercise
| mg/dL | Exercise |
|---|---|
| 1st Exercise Bout | -0.21 ± 0.13 |
| 8th Exercise Bout | -0.22 ± 0.14 |
| 16th Exercise Bout | -0.18 ± 0.07 |
| Overall | -0.20 ± 0.12 |
Serum tCa is measured to help interpret changes in iCa (e.g., changes in Ca binding) and to describe the pattern of change in tCa during and after exercise
| mg/dL | Exercise |
|---|---|
| 1st Exercise Bout | 0.01 ± 0.33 |
| 8th Exercise Bout | 0.10 ± 0.20 |
| 16th Exercise Bout | -0.02 ± 0.29 |
| Overall | 0.03 ± 0.27 |
Serum PTH is measured to assess the stimulus for the activation of bone resorption and to describe the pattern of change in PTH during and after exercise
| pg/mL | Exercise |
|---|---|
| 1st Exercise Bout | 15.4 ± 14.4 |
| 8th Exercise Bout | 16.1 ± 25.7 |
| 16th Exercise Bout | 14.0 ± 6.5 |
| Overall | 15.2 ± 16.8 |
Serum PO4 is measured because it is a potential stimulus for PTH secretion
| mg/dL | Exercise |
|---|---|
| 1st Exercise Bout | 0.19 ± 0.39 |
| 8th Exercise Bout | 0.23 ± 0.40 |
| 16th Exercise Bout | 0.10 ± 0.29 |
| Overall | 0.18 ± 0.35 |
Hct is used to adjust iCa, tCa, PTH, CTX, P1NP, and PO4 for the plasma volume contraction that occurs with exercise
| Percent | Exercise |
|---|---|
| 1st Exercise Bout | -0.38 ± 1.69 |
| 8th Exercise Bout | 0.57 ± 1.27 |
| 16th Exercise Bout | -0.33 ± 1.63 |
| Overall | -0.05 ± 1.53 |
Hgb is used to adjust iCa, tCa, PTH, CTX, P1NP, and PO4 for the plasma volume contraction that occurs with exercise
| g/dL | Exercise |
|---|---|
| 1st Exercise Bout | -0.18 ± 0.87 |
| 8th Exercise Bout | 0.23 ± 0.38 |
| 16th Exercise Bout | 0.15 ± 0.36 |
| Overall | 0.05 ± 0.61 |
HRmax is used to describe the cohort and generate individual exercise prescriptions for the intervention
| bpm | Exercise |
|---|---|
| Maximal Heart Rate (HRmax) | 170 ± 23 |
VO2peak is used to describe the cardiorespiratory fitness of the participants
| ml/kg/min | Exercise |
|---|---|
| Peak Aerobic Power (VO2peak) | 31.1 ± 8.49 |
BMD is used to describe the bone health status of the participants
| g/cm^2 | Exercise |
|---|---|
| Bone Mineral Density (BMD) | 0.967 ± 0.097 |
FM is used to describe the body composition of participants
| kg | Exercise |
|---|---|
| Fat Mass (FM) | 24.7 ± 6.5 |
FFM is used to describe the body composition of participants
| kg | Exercise |
|---|---|
| Fat-free Mass (FFM) | 56.9 ± 9.0 |
Collected over From enrollment to 24 hours after the final exercise bout, up to 12 weeks.. Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Aerobic Exercise | 0/8 (0%) | 0/8 (0%) | 2/8 (25%) |
| Event | Aerobic Exercise |
|---|---|
| Musculoskeletal painMusculoskeletal and connective tissue disorders | 2/8 |
Baseline characteristics are only reported for those who proceeded to data collection.
| Age, Continuous(Years) | Aerobic Exercise |
|---|---|
| Mean | 54.2 ± 21.4 |
| Sex: Female, Male(Participants) | Aerobic Exercise |
|---|---|
| Female | 1 |
| Male | 7 |
| Race (NIH/OMB)(Participants) | Aerobic Exercise |
|---|---|
| American Indian or Alaska Native | 0 |
| Asian | 0 |
| Native Hawaiian or Other Pacific Islander | 0 |
| Black or African American | 0 |
| White | 7 |
| More than one race | 1 |
| Unknown or Not Reported | 0 |
| Ethnicity (NIH/OMB)(Participants) | Aerobic Exercise |
|---|---|
| Hispanic or Latino | 2 |
| Not Hispanic or Latino | 6 |
| Unknown or Not Reported | 0 |
| Baseline CTX(ng/mL) | Aerobic Exercise |
|---|---|
| Mean | 0.27 ± 0.16 |
PDFs hosted by the registry, ClinicalTrials.gov.
Plan to share: Yes — Because some journals now require authors to provide access to data, de-identified, anonymized data sets (individual- and group-level data) will be created after study results are published, and made available upon requests for general research purposes, based on availability of resources. To the extent possible, care will be taken to ensure that individual-level data are at very low risk of re-identification and there will be no links to personally identifiable information.
Time frame: There is no formal plan to share these documents, although requests will be considered. Information related to the protocol and statistical analysis plan will be in the public domain when study results are published.
Access criteria: Data will become available after publication of study results and be available at least 3 years beyond the completion of the study.
This study is completed, as verified in Mar 2026. You cannot join it, but the record below documents what was studied.
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