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| ID | Type | Description | Link |
|---|---|---|---|
| W81XWH-21-1-0542 | Other Grant/Funding Number | Department of Defense, USAMRAA |
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| Name | Class |
|---|---|
| U.S. Army Medical Research and Development Command | FED |
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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:
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:
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Laboratory Based Osteogenic Index (OI) Optimized Training Group | Experimental | The OI- Optimized Training Group will involve 6 months of planned, non-linear periodized training on a leg press machine called the PPM (Athletic Republic, Salt Lake City, UT) with a maintenance program during the semester breaks, as necessary. |
|
| Laboratory Based Control Group | No Intervention | The control group will maintain their habitual exercise, diet, and sleep patterns, all of which will be monitored throughout the study. | |
| Reserve Officer Training Corps (ROTC): Observational Group | No Intervention | The ROTC group is made up of Reserve Officer Training Corps participants who are attending a university while concurrently undergoing militaristic training. This group will maintain their physical training as part of their program, diet, and sleep patterns which are monitored throughout the study. |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Osteogenic Index Optimized Exercise Training Program | Other | The OI- Optimized Training is 6 months of planned, non-linear periodized training on a leg press machine called the PPM (Athletic Republic, Salt Lake City, UT) with a maintenance program during the semester breaks, as necessary. |
| Measure | Description | Time Frame |
|---|---|---|
| Bone microarchitecture: Change in bone microarchitecture as measured via High Resolution- peripheral Quantitative Computed Tomography, change from baseline, mean | Through study completion, an average of 6 months. | |
| Bone strength: Change in bone strength as measured via High Resolution- peripheral Quantitative Computed Tomography, change from baseline, mean | Through study completion, an average of 6 months |
| Measure | Description | Time Frame |
|---|---|---|
| Biochemical: Change in concentration of Bone alkaline phosphatase (BAP), change from baseline, mean | BAP is a bone formation marker. | Through study completion, an average of 6 months |
| Biochemical: Change in concentration of Procollagen type I N-terminal Propeptide (P1NP), change from baseline, mean |
| Measure | Description | Time Frame |
|---|---|---|
| Body composition: Change in Dual Energy X-Ray Absorptiometry lean mass, change from baseline, mean | Through study completion, an average of 6 months | |
| Bone characteristics: Change in Areal Bone Mineral Density, change from baseline, mean | Through study completion, an average of 6 months |
Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Kristen J Koltun, PhD | University of Pittsburgh | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Kansas, Jayhawk Performance Laboratory | Lawrence | Kansas | 66045 | United States | ||
| Neuromuscular Research Laboratory |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 25353669 | Background | 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. | |
| 22933025 |
| Label | URL |
|---|---|
| Neuromuscular Research Laboratory Website | View source |
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Individual participant data that underlie the results reported, after identification (text, tables, figures, and appendices).
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Beginning 1 year and ending 5 years following publication.
Investigators whose proposed use of the data has been approved by an independent review committee ("learned intermediary") identified for this purpose. For individual participant data meta-analysis. Proposals should be directed to bnindl@pitt.edu. To gain access, data requesters will need to sign a data access agreement.
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| ICF | No | No | Yes | Informed Consent Form | Apr 16, 2024 | Apr 3, 2025 | ICF_000.pdf |
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| ID | Term |
|---|---|
| D009043 | Motor Activity |
| ID | Term |
|---|---|
| D001519 | Behavior |
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|
P1NP is a bone formation marker. |
| Through study completion, an average of 6 months |
| Biochemical: Change in concentration of Tartrate-resistant acid phosphatase 5b (TRAP5b), change from baseline, mean | TRAP5b is a bone resorption marker. | Through study completion, an average of 6 months |
| Biochemical: Change in concentration of Beta Cross-linking Telopeptide of type I (B-CTx) collagen, change form baseline, mean | B-CTx is a bone resorption marker. | Through study completion, an average of 6 months |
| Bone characteristics: Change in amount of Bone Marrow Adipose Tissue, change from baseline, mean | Through study completion, an average of 6 months |
| Biochemical: Change in extracellular vesicle size, change from baseline and through study completion, mean | This is a descriptive analysis in which the mean size of the extracellular vesicles will be assessed via nanoparticle tracking analysis between groups and throughout the study. | Through study completion, an average of 6 months |
| Biochemical: Change in extracellular vesicle constituent cargo, change from baseline and through study, mean | This is a descriptive analysis in which the mean contents of the extracellular vesicles will be assessed via proteomics between groups and throughout the study. | Through study completion, an average of 6 months |
| Biocehmical: Rate of change in micro- RNA expression, from baseline through study completion, Log2 Fold Change between groups | A descriptive analysis will be performed in which the micro-RNA expression in each group will be compared via the Log2 Fold Change (a type of rate of change) mathematical formula (Log2 Fold Change (LogFC): log2(Expression Level (Group 1) / Expression Level (Group 2))). | Through study completion, an average of 6 months |
| Pittsburgh |
| Pennsylvania |
| 15203 |
| United States |
| 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. |
| 19520194 | Background | 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. |
| 26453497 | Background | 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. |
| 21539165 | Background | 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. |
| 23616150 | Background | 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. |
| 30107255 | Background | 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. |
| 23684921 | Background | 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. |
| 32589957 | Background | 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. |
| 29320704 | Background | 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. |
| 24237962 | Background | 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. |
| 18089564 | Background | 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. |
| 18280232 | Background | 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. |
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| 41744293 | Derived | Kargl CK, Nindl BC, Goulart JB, Feigel ED, Sahu A, Fazeli PK, Lee AL, Rajasundaram D, Ambrosio F, Hubal MJ, Lovalekar MT, Martin BJ, Sterczala AJ, Koltun KJ. Varying Influence of Menstrual Cycle Phase and Hormonal Contraceptive Use on Resistance Exercise-Induced Circulating Extracellular Vesicle and Metabolite Signalling. J Extracell Vesicles. 2026 Mar;15(3):e70244. doi: 10.1002/jev2.70244. |