Can bone marrow composition predict bone loss?
The proposed project aims to explore the inter-relationships between bone, marrow and fat associated with osteoporosis. The primary aim is to test in an animal model, our hypothesis that changes in spongy bone volume fraction are dependent upon the proportion of red (haematopoietic) to yellow (adipose) marrow and the bone-marrow surface area. Bone remodelling rates will be compared with quantitative measurements of marrow composition and bone structure by quantitative micro magnetic resonance spectroscopy and imaging respectively. This study has significant potential to inform our understanding of bone physiology in the aging skeleton, and in particular to identify 'fast bone losers' associated with some cancer treatments and osteoporosis.
- Principal Investigators: Prof CM Langton, Prof Jim Pope, Dr Laura Gregory, Dr Mark Wellard, Dr Roland Steck, A/Prof Gustavo Duque, Prof Clive Baldock
- Associate Investigators: Dr David Mangham (UK), Dr Gary Liney (UK)
- Research Grant Submission: ARC - Discovery Project Grant
Pathophysiology of Bone Marrow
There are two types of bone marrow, red (actively involved in formation of blood cells, termed hematopoiesis) and yellow (rich in fat cells termed adipocytes). At birth, red marrow is present throughout the skeleton and converts to yellow marrow as the child grows older, occurring first in the extremities of the hands and feet. The adult pattern is characterised by the presence of red marrow in the central skeletal bones such as the spinal vertebrae, ribs, skull, and hip bones, with approximately a 10% decrease in red marrow for each decade of life.
Bone, marrow and fat are all interlinked, although the nature of the relationships is complex and has not been clarified to date. Bone tissue and bone marrow function as a single physiological unit, their blood supply being directly connected. The stem cell precursors of both osteoclasts and osteoblasts are within bone marrow and exert an important regulatory role on both their own development and on their inter-linked remodelling process.
There is evidence that the rate of bone turnover is higher at cancellous bone sites perfused with red haematopoietic marrow than where fatty marrow predominates. We know that the rate of bone loss associated with osteoporosis is variable within the skeleton, being highest in central bones such as the spinal vertebrae, and lowest in peripheral bones such as the calcaneus in the heel. Further, the response to osteoporosis treatment is higher in the central than peripheral skeleton.
Both spinal vertebrae and the calcaneus are formed predominantly from a core of spongy cancellous bone with a thin shell of solid (cortical) bone and have similar porosities. However, a parameter that is significantly higher in the central than the peripheral skeleton is the proportion of red bone marrow that perfuses the interior of all bones.
We therefore hypothesise that quantification of bone marrow composition may predict the rate of bone loss associated with osteoporosis, and aim to test this using magnetic resonance spectroscopy and imaging within an animal model of induced osteoporosis. We also hypothesise that bone marrow composition may predict the response to treatment.