Enhancing Skeletal Adaptations to PTH and Exercise

NCT05029128 | Completed DMC

• 2 other identifiers: ENDB-007-20F1 I01 CX00284
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Exercise; Bone Resorption; Bone Formation

Keywords

Acute exercise; Exercise training; Bone resorption; Bone formation; Parathyroid hormone; Calcium homeostasis

Outcome Measures

Primary Outcomes (2)

• 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.

  The primary outcome for Aim 1 is the change in CTX (dCTX) from before exercise to the peak during 4 hours of recovery measured during the 1st, 8th, and 16th exercise sessions.

• 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.

  The primary outcome for Aim 2 is the change in the pre-exercise P1NP (15 minutes before the start of exercise) from the 1st to the 16th exercise session.

Secondary Outcomes (8)

• P1NP

  Serum P1NP is measured before (-15, 0 minutes), during (15, 30, 45, 60 minutes), and after (15, 30, 60, 120, 180, 240 minutes, 24 hours) the 1st, 8th, and 16th exercise sessions

• Urinary calcium excretion (uCa)

  Urinary Ca excretion is measured over the 4 hours of recovery after the 1st, 8th, and 16th exercise sessions

• Serum ionized Ca (iCa)

  Serum iCa is measured before (-15, 0 minutes), during (15, 30, 45, 60 minutes), and after (15, 30, 60, 120, 180, 240 minutes, 24 hours) the 1st, 8th, and 16th exercise sessions

• Serum total Ca (tCa)

  Serum tCa is measured before (-15, 0 minutes), during (15, 30, 45, 60 minutes), and after (15, 30, 60, 120, 180, 240 minutes, 24 hours) the 1st, 8th, and 16th exercise sessions

• Serum parathyroid hormone (PTH)

  Serum PTH is measured before (-15, 0 minutes), during (15, 30, 45, 60 minutes), and after (15, 30, 60, 120, 180, 240 minutes, 24 hours) the 1st, 8th, and 16th exercise sessions

Other Outcomes (5)

• Maximal heart rate (HRmax)

  HRmax is measured at baseline during a maximal treadmill test

• Peak aerobic power (VO2peak)

  VO2peak is measured at baseline during a maximal treadmill test

• Bone mineral density (BMD)

  BMD of the lumbar spine and proximal femur is measured at baseline

Study Arms (1)

Exercise

OTHER

All participants engage in exercise training

Behavioral: Endurance exercise intervention

Interventions

Endurance exercise intervention BEHAVIORAL

All participants engage in treadmill walking 4 days/week, 60 minutes/day, at 70-80% of HRmax for 4 weeks.

Exercise

Eligibility Criteria

• Age: 25 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 postmenopausal, 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.

You may not qualify if:

• Initiation or change in dose in the past 6 months of medications that affect bone metabolism
• e.g., osteoporosis medications, thiazide/loop diuretics, systemic glucocorticoids
• BMD T-score \<-2.5 at the total hip, femoral neck, or lumbar spine
• Impaired renal function, defined as an estimated glomerular filtration rate (eGFR) \<60 mL/min/1.73m2
• Abnormal alkaline phosphatase
• Untreated 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
• Serum 25(OH)D \<20 ng/mL
• Uncontrolled hypertension (resting systolic blood pressure (BP) \>150 mmHg or diastolic BP \>90 mmHg)
• Type 1 diabetes
• Type 2 diabetes if on insulin or sulfonylurea therapy
• hemoglobin A1c \>7%
• 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 by a cardiologist
• Anemia (hemoglobin \<12.1 g/dL for women, \<14.3 g/dL for men)

Sponsors & Collaborators

• VA Office of Research and Development: lead

Study Sites (1)

Rocky Mountain Regional VA Medical Center, Aurora, CO

Aurora, Colorado, 80045-7211, United States

Location

MeSH Terms

Conditions

Motor Activity; Bone Resorption

Condition Hierarchy (Ancestors)

Behavior; Bone Diseases; Musculoskeletal Diseases

Study Officials

• Wendy M Kohrt, PhD

  Rocky Mountain Regional VA Medical Center, Aurora, CO

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: FED
• Responsible Party: SPONSOR

Model Details: All participants will undergo the same exercise intervention for this proof-of-concept project, so there is no randomization. The exercise will be treadmill walking at 70-80% of HRmax for 60 min/d, 4 d/wk, for 4 wk. The mode and intensity of exercise were selected because high-intensity weight-bearing exercise is recommended for bone health, and walking is the most common weight-bearing activity. Although "high-intensity" exercise for bone health refers to the intensity of bone-loading forces, %HRmax is a good proxy because peak bone-loading forces increase as walking or running speed increases. Exercise sessions will be supervised by the research team. This exercise prescription was used in the studies of young and older adults that provided the scientific premise for the current study and resulted in robust PTH and CTX responses.

Study Record Dates

• First Submitted: August 12, 2021
• First Posted: August 31, 2021
• Study Start: January 1, 2023
• Primary Completion: April 1, 2025
• Study Completion: December 1, 2025
• Last Updated: December 29, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will share
• 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.

Locations

US (1)