Osteoporosis is one of the leading health problems in the United States. Recent studies suggest that adipocytes in bone marrow and osteoblasts share the same precursor, mesenchymal stem cells (MSC). Human imaging studies [i.e., magnetic resonance spectroscopy (MRS), magnetic resonance imaging (MRI) and computed tomography (CT)] have also shown that there is an inverse relationship between bone marrow adipose tissue (BMAT) and bone mineral density (BMD). It is unknown whether this inverse relationship represents a preferential differentiation of stromal cells from osteoblasts to adipocytes, or a passive accumulation of fat as bone is lost and marrow space increases with aging. A clearer understanding of the relationship between bone mineral and marrow fat is a critical first step towards the development of prevention and treatment strategies for bone loss through enhancing the osteogenic differentiation of progenitor cells. This study pools a unique database of ~1000 healthy adults all of whom have both whole body MRI and DXA data which are otherwise very expensive to collect. The proposed aim is to investigate the relationship between BMAT by whole body MRI and BMD by dual-energy x-ray absorptiometry (DXA) in a subject-diverse database. Previous studies using MRS and CT methods are usually limited to measuring BMAT in a small volume usually within a single bone. Lack of BMAT homogeneity in the cavity of a single bone or across bones presents as one of the reasons why studies using MRS to quantify BMAT report a lower correlation between BMAT and BMD compared to our whole body MRI methods. Our proposed MRI methods overcome the sampling limitations of MRS or CT methods by possessing the unique ability to allow for the study of BMAT of multiple cancellous bones. The proposed study will examine whether there are differences between the association of BMAT and BMD in young adults who have achieved or are close to their peak bone mass and older adults with potential bone loss. If there is a strong inverse correlation between BMAT and BMD in both younger/peak bone mass subjects and older/potential bone loss subjects, the results would support the hypothesis that lower BMD is related to a preferential differentiation of stromal cells from osteoblasts to adipocytes. Alternatively, if a strong inverse relationship between BMAT and BMD exists only in older adults who potentially have bone loss but not in younger adults, either passive accumulation of fat or preferential differentiation of MSC from osteoblasts to adipocytes could explain the pathophysiology related to aging. Furthermore, this unique diverse large scale MRI and DXA database will allow us to first systematically investigate potential gender and ethnic differences in the relationship between bone and marrow fat. The findings from these studies will contribute significantly to understanding the interplay between marrow fat and bone and will complement and provide direction for ongoing molecular studies and drug development studies as clinical evidence.
A large database of approximately 1000 archived whole body magnetic resonance imaging (MRI) scans collected as part of previously funded body composition studies will be analyzed using imaging software to quantify bone marrow fat in each subject scan. By comparing the relationship between marrow fat and bone mineral in younger and older subjects, important evidence will be obtained on whether there is a competitive relationship between marrow fat and bone mineral which will complement molecular level studies.
