Bone Response to Exercise and Energy Restriction in Young Adults

Bone Response to Exercise Before and After One Week of Energy Restriction in Young Adults

Cycling is commonly questioned whether it provides adequate mechanical strain on bone as many elite cyclists have been found to have a low bone mass. However, it remains unclear if this is due to cycling or low energy availability. In addition, acute dietary energy restriction has been found to be accompanied by an imbalance in bone remodelling with reduced bone formation. The objective of this proposal is to examine whether short-term energy restriction leads to changes in markers of bone formation and resorption at rest and in response to cycling in young adults. Specifically, the study will examine changes in circulating bone markers in 15 males and females (ages 18-24) both at rest and following one 45-minute spinning class both before and after one week of restricted energy intake. Blood will be drawn at rest (pre-trial, fasted), and 3 times post-trial (5 min, 1h and 24h); then analysed for biochemical markers of bone formation (BAP and OPG) and resorption (CTX and RANKL) to assess the impact of energy restriction on bone at rest and in response to exercise. This innovative work has potential to make significant advances in understanding tissue growth and development in response to exercise and malnutrition.

Study Overview

• Status: Not yet recruiting
• Conditions: Bone Loss; Bone Resorption
• Intervention / Treatment: Other: Energy restriction

Detailed Description

Introduction: The skeletal system serves a variety of purposes such as providing structural support, locomotion, protection and more. In order to sustain these functions, bone strength must be upheld. The process of replacing older, microdamaged bone with newer, healthier bone is known as bone remodelling. Bone remodelling involves the balance/coupling of bone resorption and bone formation. Mechanical loading is the magnitude of stress placed on the bone that stimulates bone remodelling, which determines bone mineral density (BMD) and promotes bone growth (Olmedillas et al. 2011). Thus, human research on the determinants of bone growth and strength, is focused on two common factors, exercise and nutrition. Although cycling, a predominantly aerobic exercise, is exceptional for cardiovascular fitness, it is commonly questioned whether it provide adequate mechanical strain on bone. To date the literature surrounding cycling and its impact on bone is contradicting and limited. Inadequate energy intake may also influence BMD via reductions in bone mineral content. Energy restriction is known to reduce insulin-like growth factor 1 (IGF-1), which plays an important role in bone formation 5. Acute dietary energy restriction has been found to be accompanied by an imbalance of bone remodelling with reduced bone formation, which is especially dangerous in aerobic sports that expend a great amount of energy, such as cycling. Many professional and master cyclists are classified as osteopenic (Medelli et al. 2000). Specifically, female cyclists have shown significant lower values of whole-body BMD, and a lower bone strength, than male cyclists (Olmedillas et al. 2011). In addition, female cyclists are known to be energy deficient (low calorie intake) with the average energy intake being 85% of the Recommended Dietary Allowance (RDA). Therefore, it is important to understand whether cycling is a poor form of exercise for bone health or whether the energy restriction, alone or in combination with cycling, is the true underlining issue.

Objective: The objective of this study is to examine whether short-term energy restriction leads to changes in markers of inflammation, oxidative stress, bone turnover at rest and in response to cycling in young adults. Specifically, the study will examine changes in circulating bone markers at rest and following one bout of low impact 45-minute spinning (cycling) both before and after one week of restricted energy intake.

Methods: Fifteen healthy males and females, aged 20-25 years, will be invited to participate in this study, which involves one control trial and two exercise trial visits scheduled one week apart. Females will be on monophasic oral contraceptives, During the control trial, participants will be briefed on the purpose and procedures, will fill out an exercise screening questionnaire, and will provide 4 resting blood samples. One week later, participants will perform the first exercise trial of one 45 minute spin session. Following the first trial, the participants will go on a predetermined energy deficient diet (25% of their habitual diet) for one week, at the end of which they will perform the second trial following the same cycling protocol. Between the first and last visit the participants will be receiving a Fitbit to monitor their activity (steps, heart rate, physical activity participation) and nutritional habits in a food log. To keep the diet consistent and standardized, participants will also be asked to record their habitual food intake during the control week using the "Eat This Much" app, which will provide an overall portion plan and a 25% caloric restriction measure for the intervention week. Thus, the intervention diet will mirror the control diet in terms of types of food consumed, with the difference being in the amount consumed. There will be no restriction regarding water, but drinks will be restricted according to the overall calorie intake plan.In both trials, blood will be drawn at rest (i.e., pre-trial, fasted), and 3 times post-trial (5 min, 1h and 24h). The blood will be centrifuged and the serum separated, aliquoted and then stored at -80 °C until analysis 8. The serum will be analysed for biochemical markers of bone turnover (e.g. osteocalcin, bone-specific alkaline phosphatase [BAP]; osteoprotegerin [OPG]) and bone resorption (C-telopeptides of type I collagen [CTX]; receptor activator of nuclear factor κB ligand [RANKL], sclerostin) to assess the impact of energy restriction on bone at rest and in response to exercise. Metabolic and oxidative stress markers, inflammatory cytokines, adipokines, growth factors and hormones will also be assessed to examine potential mediating effects.

Impact: This innovative work has the potential to make significant advances in understanding the impact of energy restriction and cycling on bone health. The findings from this work will be translatable to understanding tissue growth and development in response exercise and malnutrition.

• Study Type: Interventional
• Enrollment (Estimated): 12
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Panagiota Klentrou, PhD; Phone Number: 4538 1-905-688-5550; Email: nklentrou@brocku.ca
• Study Contact Backup: Name: Madison Bell, BSc; Phone Number: 1-705-279-3113; Email: mb14pf@brocku.ca

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 25 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Caucasian males and females, aged 20 to 25 years
• healthy (not suffering from asthma)
• without any fracture over the last year
• not taking any medication related to a chronic condition or bone health including food/nutritional supplements (e.g. protein, vitamin D, calcium)
• nonsmokers
• females on monophasic oral contraceptives.

Exclusion Criteria:

• Injuries or chronic conditions in which exercise may pose a risk (e.g., ACL or knee/hip/lower back injuries, arthritis, osteoporosis, neuromuscular diseases)
• any restrictive food allergies or dietary restrictions that would require alterations to the diet plan (i.e, vegan, vegetarian) and or
• any eating disorders (e.g., bulimia, and or anorexia)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Participants; For a period of 6 days between the exercise trials (i.e., following visit 3), each participant will be put on a restricted energy restricted diet consisting of a 25% reduction in their habitual total daily calorie intake. To keep the diet consistent and standardized, participants will record their typical food intake during a control week using the "Eat This Much" app, which will then provide an overall portion plan and the 25% caloric restriction measure for the intervention week. Thus, the intervention diet will mirror the control diet in terms of types of food consumed, with the difference being in the amount consumed. There will be no restriction regarding water, but drinks will be restricted according to the overall calorie intake plan.

Other: Energy restriction; A 25% reduction in total caloric intake, as calculated through the app. Therefore, during the control period, participants will input what they consume into the Eat This Much app, then the app will calculate the 25% reduction in calories to present participants with how much to consume of the same foods. By doing this their diet will not be altered in terms of macronutrients or micronutrients, but solely on calories.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Bone turnover marker	Osteocalcin in ng/ml	one week
Bone formation marker	Bone-specific alkaline phosphatase [BAP] in ng/ml	one week
Bone resorption marker	C-telopeptides of type I collagen [CTX] in ng/ml	one week
Bone formation osteokine	Osteoprotegerin [OPG] in ng/ml	one week
Bone resorption osteokine	Receptor activator of nuclear factor κB ligand [RANKL] in ng/ml	one week
Wnt signaling related osteokine	Sclerostin in ng/ml	one week
Anti-inflammatory cytokine	Interleukin 10 [IL-10] in pg/ml	one week
Pro-inflammatory cytokine	Tumor necrosis factor alpha (TNF-α) in pg/ml	one week
Myokine	Interleukin 6 [IL-6] in pg/ml	one week
Irisin	Irisin in pg/ml	one week
Oxidative stress marker	protein carbonyls (PC) in mmol/mg serum protein	one week

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Body mass	Total body mass in kg	one week
Lean body mass	Fat-free mass in kg	one week
Fat body mass	Fat mass in kg	one week

Collaborators and Investigators

• Sponsor: Brock University
• Collaborators: Natural Sciences and Engineering Research Council, Canada
• Investigators: Principal Investigator: Panagiota Klentrou, PhD, Brock University

Publications and helpful links

General Publications

• Olmedillas H, Gonzalez-Aguero A, Moreno LA, Casajus JA, Vicente-Rodriguez G. Bone related health status in adolescent cyclists. PLoS One. 2011;6(9):e24841. doi: 10.1371/journal.pone.0024841. Epub 2011 Sep 30.
• Medelli J, Lounana J, Menuet JJ, Shabani M, Cordero-MacIntyre Z. Is osteopenia a health risk in professional cyclists? J Clin Densitom. 2009 Jan-Mar;12(1):28-34. doi: 10.1016/j.jocd.2008.07.057. Epub 2008 Oct 1.

Study record dates

Study Major Dates

• Study Start (Estimated): September 1, 2024
• Primary Completion (Estimated): March 24, 2025
• Study Completion (Estimated): December 18, 2025

Study Registration Dates

• First Submitted: April 10, 2020
• First Submitted That Met QC Criteria: April 13, 2020
• First Posted (Actual): April 14, 2020

Study Record Updates

• Last Update Posted (Estimated): December 18, 2023
• Last Update Submitted That Met QC Criteria: December 15, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Keywords: biomarkers; bone; diet; females; youth; cycling
• Additional Relevant MeSH Terms: Musculoskeletal Diseases; Bone Diseases; Bone Resorption
• Other Study ID Numbers: REB 19-247

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No