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.
The proportion of the U.S. population older than 65 years will increase from 12.7% in 2000 to 20.3% in 2050, and the number of fractures is expected to exceed 3 million by 2025 with associated costs in the order of $25.3 billion per year. DAMES is an ongoing clinical trial (NCT03227458) that aims to assess -for the first time- changes in areal bone mineral density (aBMD) and fat-free mass (FFM) in response to therapy with the adrenal steroid dehydroepiandrosterone (DHEA) alone and combined with bone-loading exercise (EX) in older women with bone loss. The hormonal and mechanical strategies proposed in DAMES represent a low-cost alternative treatment to improve bone quantity with a number of other health benefits not afforded by typical pharmacological approaches. However, bone strength -the main determinant of bone fracture- is a function of not only BMD and microstructure, but also of its microenvironment, including bone marrow fat (BMF). This in an ancillary study to the DAMES clinical trial. Here, the investigators propose to leverage the well-characterized cohort of subjects, exercise training, clinical, laboratory and imaging data from DAMES, and add a small group of controls to its three existing arms (DHEA only, EX+Placebo, and EX+DHEA) to investigate the effects of DHEA therapy and EX on BMF in older women using advanced imaging, numerical engineering, and image analysis techniques. In particular, the investigators aim to determine in the lumbar spine and hip of older women with low bone mass or moderate osteoporosis: 1) whether DHEA or EX leads to changes in BMF content; 2) whether BMF content is associated with bone strength at baseline, and whether changes in BMF content are associated with changes in bone strength, evaluating the impact of DHEA or EX on these associations; and 3) the spatial distribution of changes in BMF content in response to DHEA or EX. BMF will be measured with chemical shift-based water-fat separation magnetic resonance imaging, bone strength will be estimated with finite element modeling from quantitative computed tomography scans, and differences in the spatial distribution of BMF changes between groups will be assessed using voxel-based morphometry. Ultimately, the investigators will leverage the DAMES clinical trial to unveil new information to improve our understanding of DHEA and EX on bone quantity and quality. The longitudinal assessments of bone quality in this ancillary proposal, with those of bone quantity in the parent study, in women who have already lost bone mass is unprecedented. Understanding how osteoporosis treatments -including exercise- act on BMF could lead to the generation of novel approaches for fracture risk assessment, procedures for therapy monitoring, and treatments for bone loss.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
PREVENTION
Masking
TRIPLE
Enrollment
41
University of Colorado Anschutz Medical Campus
Aurora, Colorado, United States
Changes in spine bone marrow fat content
changes in bone marrow fat content of the lumbar spine
Time frame: 36 weeks
Changes in hip bone marrow fat content
changes in bone marrow fat content of the proximal femur
Time frame: 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
Time frame: 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
Time frame: 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)
Time frame: 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)
Time frame: 36 weeks
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