Effects of DHEA and Exercise on Bone Marrow Fat in Postmenopausal Women

NCT05316272 | Completed DMC

• 2 other identifiers: 162427a5R01AR077924-03
• Study Type: interventional
• Target: 41
• Locations: 1 country
• Sites: 1

Brief Summary

Bone strength -the main determinant of bone fracture- is a function not only of bone mineral density (BMD) and microstructure, but also of its microenvironment, including bone marrow fat (BMF). The adrenal steroid dehydroepiandrosterone (DHEA) -the main precursor for estrogens and androgens in postmenopausal women- as well as bone-loading exercise, increase BMD in older women, however, their effects on BMF are largely unknown. This study has high potential to unveil the hormonal and mechanical effects of DHEA and exercise on BMF, respectively, and to elucidate longitudinal associations of BMF with bone strength in older women with bone loss.

Conditions

Low Bone Density; Osteoporosis

Outcome Measures

Primary Outcomes (6)

• Changes in spine bone marrow fat content

  changes in bone marrow fat content of the lumbar spine

  36 weeks

• Changes in hip bone marrow fat content

  changes in bone marrow fat content of the proximal femur

  36 weeks

• Correlation of lumbar spine bone marrow fat content with bone strength at baseline

  Correlation of lumbar bone marrow fat content (%) with strength (N) of the lumbar spine at baseline

  baseline - 0 weeks of intervention

• Correlation of hip bone marrow fat content with hip strength at baseline

  Correlation of proximal femur spine bone marrow fat content (%) with strength (N) of the proximal femur at baseline

  baseline - 0 weeks of intervention

• Correlation of the changes in spine bone marrow fat content with changes in spine bone strength

  Correlation of the changes in lumbar spine bone marrow fat content (%) with changes in lumbar spine strength (N)

  36 weeks

• Correlation of the changes in hip bone marrow fat content (%) with changes in hip bone strength (N)

  Correlation of the changes in proximal femur bone marrow fat content (%) with changes in proximal femur bone strength (N)

  36 weeks

Other Outcomes (2)

• spatial distribution of the changes in bone marrow fat content of the spine

  36 weeks

• spatial distribution of the changes in bone marrow fat content of the hip

  36 weeks

Study Arms (4)

Exercise and placebo

EXPERIMENTAL

supervised bone-loading exercise 3 days per week and one placebo pill per day for 36 weeks

Behavioral: Exercise; Dietary Supplement: DHEA

Exercise and DHEA

EXPERIMENTAL

supervised bone-loading exercise 3 days per week and one dose of DHEA (50 milligrams) per day for 36 weeks

Behavioral: Exercise; Dietary Supplement: DHEA

no exercise and DHEA

EXPERIMENTAL

no supervised bone exercise and one dose of DHEA (50 milligrams) per day for 36 weeks

Behavioral: Exercise; Dietary Supplement: DHEA

no exercise and placebo

EXPERIMENTAL

no supervised bone-loading exercise and one placebo pill per day for 36 weeks

Behavioral: Exercise; Dietary Supplement: DHEA

Interventions

Exercise BEHAVIORAL

Supervised bone-loading exercise on 3 days per week for 36 weeks

Exercise and DHEA; Exercise and placebo; no exercise and DHEA; no exercise and placebo

DHEA DIETARY_SUPPLEMENT

DHEA in pill form 50 milligrams taken daily for 36 weeks

Exercise and DHEA; Exercise and placebo; no exercise and DHEA; no exercise and placebo

Eligibility Criteria

• Age: 55 Years - 85 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• women aged 55 to 85 years
• non-frail, as determined by Short Physical Performance Battery score \> 9 (0-12 scale)
• years or longer since menopause (defined as last menstrual period)
• willing to participate in a 36-week exercise program that will start at a moderate intensity and gradually progress to a higher intensity
• willing to take DHEA (50mg/d) or a placebo pill daily and remain blinded for up to 36 weeks
• not performing resistance exercise training or high impact weight-bearing exercise (e.g., jogging) ≥ 2 days per week in the past 6 months
• ambulatory without assistive devices
• serum DHEAS \< 140 μg/dL (3.8 μmol/L)
• low bone mass or moderate osteoporosis indicated by lumbar spine, total hip, or femoral neck aBMD t-scores \< -1.0 and ≥ -3.0
• refusal of standard osteoporosis treatment in women with moderate osteoporosis (BMD ≥-3.0 and ≤ -2.5)
• evidence of a negative (no findings suspicious for breast cancer) mammogram within the past 12 months
• planning to reside in the Denver area for the duration of the study
• willing to provide evidence of completed COVID-19 vaccination
• no implanted metal or electronic devices
• no metallic foreign body in the eye

You may not qualify if:

• history of hospitalization for Corona Virus Disease 2019 (COVID-19)
• does not meet Centers for Disease Control and Prevention (CDC) recommendations for home isolation because has had a positive severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) test less than 10 days before study entry; or has had fever within the past 3 days and respiratory symptoms have not improved; or symptoms first appeared less than 10 days before study entry.
• not willing to provide evidence of completed COVID-19 vaccination.
• uncontrolled hypertension defined as resting systolic BP \>150 mmHg or diastolic BP \>90 mmHg; participants who do not meet these criteria at first screening will be re-evaluated, including follow-up evaluation by their primary care provider (PCP) with initiation or adjustment of anti-hypertensive medications.
• diagnosis of heart failure, clinically significant aortic stenosis, uncontrolled angina, or uncontrolled arrhythmia.
• pulmonary disease requiring use of oral steroids within the previous 6 months or the use of supplemental oxygen ≥ 4 liters with physical exertion
• orthopedic problems (e.g., severe osteoarthritis, rheumatoid arthritis) that greatly limit the ability to perform moderate to high intensity resistance exercise (e.g., unable to be properly positioned in exercise equipment or to have severely restricted range of motion even after modifications have been made)
• hip fracture, hip or knee replacement, or spinal surgery in the past 6 months
• undergoing physical therapy involving the lower extremities
• hematocrit \> 54%
• thyroid dysfunction, defined as an ultrasensitive thyroid stimulating hormone (TSH) \< 0.4 or \> 10 micro units/mL, without signs or symptoms of clinical hypo- or hyperthyroidism.volunteers with abnormal TSH values will be re-considered for participation in the study after follow-up evaluation by their PCP with initiation or adjustment of thyroid hormone replacement
• acute liver disease indicated by liver function tests (ALT, aspartate aminotransferase, alkaline phosphatase) ≥ 1.5 times the upper limits of normal
• estimated glomerular filtration rate (eGFR) \< 45, using Modification of Diet in Renal Disease Study (MDRD) equation
• poorly controlled diabetes mellitus based on HbA1c \> 8.5% or use of insulin.
• fasted serum triglycerides \> 400 mg/dL

Sponsors & Collaborators

• University of Colorado, Denver: lead
• National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS): collaborator

Study Sites (1)

University of Colorado Anschutz Medical Campus

Aurora, Colorado, 80045, United States

Location

MeSH Terms

Conditions

Bone Diseases, Metabolic; Osteoporosis

Interventions

Exercise; Dehydroepiandrosterone

Condition Hierarchy (Ancestors)

Bone Diseases; Musculoskeletal Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Motor Activity; Movement; Musculoskeletal Physiological Phenomena; Musculoskeletal and Neural Physiological Phenomena; Androstenols; Androstenes; Androstanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; 17-Ketosteroids; Ketosteroids; Adrenal Cortex Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Testosterone Congeners; Gonadal Steroid Hormones; Gonadal Hormones

Study Officials

• Catherine Jankowski, PhD

  University of Colorado, Denver

  PRINCIPAL INVESTIGATOR

• Julio Carballido-Gamio, PhD

  University of Colorado, Denver

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Masking of the study pill (DHEA or placebo) is described as noted above. Exercise cannot be masked.
• Purpose: PREVENTION
• Intervention Model: FACTORIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Two-by-two crossed design of DHEA versus control and exercise versus no exercise control.

Study Record Dates

• First Submitted: March 17, 2022
• First Posted: April 7, 2022
• Study Start: March 11, 2022
• Primary Completion: June 30, 2024
• Study Completion: June 30, 2024
• Last Updated: December 10, 2024

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)