Clinical trial NCT06972862: Bone and Body Composition Adaptations to Physical Training
Official title: Optimizing Muscle and Bone Mechanoadaptation to Physical Training: Mechanistic Control Paths Via Muscle and Bone Crosstalk to Altered Mechanical Loading
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Exercise
Healthy
Keywords: bone health
body composition
skeletal muscle
hormones
exercise intervention
recreational athletes
bone marrow adipose tissue
bone formation
bone resportion
bone geometry
bone microarchitecture
bone mineral density
Lead sponsor: University of Pittsburgh
Sponsor class: OTHER
Collaborators: name: U.S. Army Medical Research and Development Command
First posted: 2025-05-15
Enrollment: 206
Sex: ALL
Minimum age (years): 18
Maximum age (years): 40
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

Brief summary: The goal of this clinical trial is to evaluate how different exercise programs alter bone density, structure, and strength in adults. It will also collect data on hormones, factors released from skeletal muscle, and body composition.

The main questions it aims to answer are:

* Do exercise programs that are frequent with high-impact loading will cause greater improvements in bone health?
* What changes in hormones, factors released from skeletal muscle, and body composition contribute to bone adaptations?

Researchers will compare different exercise groups to see if the type of exercise influences bone adaptation compared to a recreationally active control group.

Participants are asked to:

* complete questionnaires, 5 blood draws across the study (3 at rest, 2 after strenuous exercise), dual energy x-ray absorptiometry (DXA) scans (to assess bone mineral density and body composition), high resolution tibial scans to assess bone structure and geometry, and physical performance testing.
* attend up to 7 testing visits.
* (for those randomized to the exercise training intervention) participate in exercise training sessions for 6 months.

Detailed description: The overall objective of this study is to determine the bone density, structure and strength adaptations that result from various exercise programs which differ based on the frequency and intensity of bone loading. Bone adaptation is measured with both dual-energy x-ray absorptiometry (DXA), the standard-of-care equipment used to evaluate bone mineral density (BMD), and high-resolution peripheral quantitative computed tomography (HRpQCT), a state-of-the-science imaging technology providing the resolution necessary to detect small but clinically relevant changes.

Additionally, the research team seeks to determine the physiological responses and adaptations to training that contribute to improved bone health by evaluating changes in hormones, factors released from active skeletal muscle, and body composition. Our hypothesis is that exercise programs emphasizing frequent, high impact loading will cause greater improvements in bone health. Additionally, we believe that exercise training can induce specific changes in hormones, skeletal muscle released signaling factors and body composition that contribute to these bone adaptations.

Participants who enrolled in this study were randomized to either an exercise training group or a control group who were instructed to maintain their current level of exercise and track this to report to the study team. Study completers were those who complied with the parameters of the group they were assigned and reported to all 7 testing visits.

Eligibility criteria: Inclusion Criteria:

1. Age 18-40 years
2. Body mass index (BMI) 18-28 kg/m2
3. Weight stable (±10 lbs) in past 2 months
4. Takes part in moderate physical activity for at least 150 minutes/week
5. Currently free of upper or lower body /extremity injury or impairment
6. Comfortable with multiple blood draws
7. Able to commit to the 6-month study duration
8. Agrees to adhere to study requirements.

Exclusion Criteria:

1. Current smoker
2. Current clinical diagnosis of an eating disorder
3. Chronic use of non-steroidal anti-inflammatory drugs (NSAIDs). NSAID use is defined as chronic if these medications are taken more than three times a week for more than 12 consecutive weeks.
4. Use of medication incompatible with measurement of reproductive, metabolic, or bone-related hormones (including thyroid medications, glucocorticoids) or which includes anti-coagulants and may interfere with any of the study outcomes
5. Current oligo/amenorrhea in women, not explained by contraceptive use
6. Any metabolic or endocrine disease that affects bone; Individuals taking hormonal therapy for transgender care
7. Currently training for a competitive sporting event or planning to start
8. Weight has fluctuated by 10 pounds or more in the past 2 months based on subject self-report
9. Has been diagnosed with a medical condition, physical or psychological, that currently prevents exercise participation
10. Has suffered a musculoskeletal injury removing them from physical activity for more than a month, within the past two years
11. Currently pregnant or becomes pregnant during the study (as assessed by urine pregnancy tests at 0, 3 \& 6 months)
12. Current asthma diagnosis, defined as experienced symptoms or been prescribed any form of treatment within the last 4 years, or those who have required more than one course of oral steroids or more than one nebulization since the age of 5 (JSP 950), will require a note/permission from treating physician to participate in study. Those who have had a single admission to intensive care or high dependency, or multiple admissions to hospital will be excluded from participating (JSP 950)
13. History of heart condition OR high blood pressure
14. Feeling of pain in the chest during rest, activities of daily living, or physical activity
15. Have lost balance or consciousness due to dizziness in the last 12 months (with the exception of dizziness due to hyperventilation)
16. Treating physician requires subject participates in medically supervised physical activity only
17. History of drug addiction or habitual recreational drug use (2 or more times per month in each of the previous six months)
18. Low bone mineral density indicated as a Z-score \<-1.0 measured by dual-energy x-ray absorptiometry (DXA)

Primary outcomes:
measure: Bone microarchitecture: Change in bone microarchitecture as measured via High Resolution- peripheral Quantitative Computed Tomography, change from baseline, mean
timeFrame: Through study completion, an average of 6 months.
measure: Bone strength: Change in bone strength as measured via High Resolution- peripheral Quantitative Computed Tomography, change from baseline, mean
timeFrame: Through study completion, an average of 6 months
Secondary outcomes:
measure: Biochemical: Change in concentration of Bone alkaline phosphatase (BAP), change from baseline, mean
timeFrame: Through study completion, an average of 6 months
measure: Biochemical: Change in concentration of Procollagen type I N-terminal Propeptide (P1NP), change from baseline, mean
timeFrame: Through study completion, an average of 6 months
measure: Biochemical: Change in concentration of Tartrate-resistant acid phosphatase 5b (TRAP5b), change from baseline, mean
timeFrame: Through study completion, an average of 6 months
measure: Biochemical: Change in concentration of Beta Cross-linking Telopeptide of type I (B-CTx) collagen, change form baseline, mean
timeFrame: Through study completion, an average of 6 months
measure: Bone characteristics: Change in amount of Bone Marrow Adipose Tissue, change from baseline, mean
timeFrame: Through study completion, an average of 6 months
measure: Biochemical: Change in extracellular vesicle size, change from baseline and through study completion, mean
timeFrame: Through study completion, an average of 6 months
measure: Biochemical: Change in extracellular vesicle constituent cargo, change from baseline and through study, mean
timeFrame: Through study completion, an average of 6 months
measure: Biocehmical: Rate of change in micro- RNA expression, from baseline through study completion, Log2 Fold Change between groups
timeFrame: Through study completion, an average of 6 months
Other outcomes:
measure: Body composition: Change in Dual Energy X-Ray Absorptiometry lean mass, change from baseline, mean
timeFrame: Through study completion, an average of 6 months
measure: Bone characteristics: Change in Areal Bone Mineral Density, change from baseline, mean
timeFrame: Through study completion, an average of 6 months
Locations:
city: Lawrence
country: United States
facility: University of Kansas, Jayhawk Performance Laboratory
state: Kansas
city: Pittsburgh
country: United States
facility: Neuromuscular Research Laboratory
state: Pennsylvania
Study officials:
affiliation: University of Pittsburgh
name: Kristen J Koltun, PhD
role: STUDY_DIRECTOR
References:
citation: Allaway HC, Williams NI, Mallinson RJ, Koehler K, De Souza MJ. Reductions in urinary collection frequency for assessment of reproductive hormones provide physiologically representative exposure and mean concentrations when compared with daily collection. Am J Hum Biol. 2015 May-Jun;27(3):358-71. doi: 10.1002/ajhb.22649. Epub 2014 Oct 29.
citation: Nindl BC, Urso ML, Pierce JR, Scofield DE, Barnes BR, Kraemer WJ, Anderson JM, Maresh CM, Beasley KN, Zambraski EJ. IGF-I measurement across blood, interstitial fluid, and muscle biocompartments following explosive, high-power exercise. Am J Physiol Regul Integr Comp Physiol. 2012 Nov 15;303(10):R1080-9. doi: 10.1152/ajpregu.00275.2012. Epub 2012 Aug 29.
citation: Lester ME, Urso ML, Evans RK, Pierce JR, Spiering BA, Maresh CM, Hatfield DL, Kraemer WJ, Nindl BC. Influence of exercise mode and osteogenic index on bone biomarker responses during short-term physical training. Bone. 2009 Oct;45(4):768-76. doi: 10.1016/j.bone.2009.06.001. Epub 2009 Jun 9.
citation: Carson JA, Manolagas SC. Effects of sex steroids on bones and muscles: Similarities, parallels, and putative interactions in health and disease. Bone. 2015 Nov;80:67-78. doi: 10.1016/j.bone.2015.04.015.
citation: Wentz L, Liu PY, Haymes E, Ilich JZ. Females have a greater incidence of stress fractures than males in both military and athletic populations: a systemic review. Mil Med. 2011 Apr;176(4):420-30. doi: 10.7205/milmed-d-10-00322.
citation: Rantalainen T, Nikander R, Heinonen A, Cervinka T, Sievanen H, Daly RM. Differential effects of exercise on tibial shaft marrow density in young female athletes. J Clin Endocrinol Metab. 2013 May;98(5):2037-44. doi: 10.1210/jc.2012-3748. Epub 2013 Apr 24.
citation: Singhal V, Torre Flores LP, Stanford FC, Toth AT, Carmine B, Misra M, Bredella MA. Differential associations between appendicular and axial marrow adipose tissue with bone microarchitecture in adolescents and young adults with obesity. Bone. 2018 Nov;116:203-206. doi: 10.1016/j.bone.2018.08.009. Epub 2018 Aug 11.
citation: Gorgey AS, Poarch HJ, Adler RA, Khalil RE, Gater DR. Femoral bone marrow adiposity and cortical bone cross-sectional areas in men with motor complete spinal cord injury. PM R. 2013 Nov;5(11):939-48. doi: 10.1016/j.pmrj.2013.05.006. Epub 2013 May 15.
citation: Sanford JA, Nogiec CD, Lindholm ME, Adkins JN, Amar D, Dasari S, Drugan JK, Fernandez FM, Radom-Aizik S, Schenk S, Snyder MP, Tracy RP, Vanderboom P, Trappe S, Walsh MJ; Molecular Transducers of Physical Activity Consortium. Molecular Transducers of Physical Activity Consortium (MoTrPAC): Mapping the Dynamic Responses to Exercise. Cell. 2020 Jun 25;181(7):1464-1474. doi: 10.1016/j.cell.2020.06.004.
citation: Whitham M, Parker BL, Friedrichsen M, Hingst JR, Hjorth M, Hughes WE, Egan CL, Cron L, Watt KI, Kuchel RP, Jayasooriah N, Estevez E, Petzold T, Suter CM, Gregorevic P, Kiens B, Richter EA, James DE, Wojtaszewski JFP, Febbraio MA. Extracellular Vesicles Provide a Means for Tissue Crosstalk during Exercise. Cell Metab. 2018 Jan 9;27(1):237-251.e4. doi: 10.1016/j.cmet.2017.12.001.
citation: Norheim F, Langleite TM, Hjorth M, Holen T, Kielland A, Stadheim HK, Gulseth HL, Birkeland KI, Jensen J, Drevon CA. The effects of acute and chronic exercise on PGC-1alpha, irisin and browning of subcutaneous adipose tissue in humans. FEBS J. 2014 Feb;281(3):739-49. doi: 10.1111/febs.12619. Epub 2013 Dec 10.
citation: Robling AG, Niziolek PJ, Baldridge LA, Condon KW, Allen MR, Alam I, Mantila SM, Gluhak-Heinrich J, Bellido TM, Harris SE, Turner CH. Mechanical stimulation of bone in vivo reduces osteocyte expression of Sost/sclerostin. J Biol Chem. 2008 Feb 29;283(9):5866-75. doi: 10.1074/jbc.M705092200. Epub 2007 Dec 17.
citation: Bonewald LF, Johnson ML. Osteocytes, mechanosensing and Wnt signaling. Bone. 2008 Apr;42(4):606-15. doi: 10.1016/j.bone.2007.12.224. Epub 2008 Jan 12.
citation: Evans RK, Negus CH, Centi AJ, Spiering BA, Kraemer WJ, Nindl BC. Peripheral QCT sector analysis reveals early exercise-induced increases in tibial bone mineral density. J Musculoskelet Neuronal Interact. 2012 Sep;12(3):155-64.
citation: Hughes JM, Gaffney-Stomberg E, Guerriere KI, Taylor KM, Popp KL, Xu C, Unnikrishnan G, Staab JS, Matheny RW Jr, McClung JP, Reifman J, Bouxsein ML. Changes in tibial bone microarchitecture in female recruits in response to 8 weeks of U.S. Army Basic Combat Training. Bone. 2018 Aug;113:9-16. doi: 10.1016/j.bone.2018.04.021. Epub 2018 Apr 27.