Building bone from blood: The effect of vitamin D on circulating bone-forming cells

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Bone remodelling involves a process of continuous bone resorption and formation through the co-ordinated recruitment of osteoclasts (bone resorbing cells) and osteoblasts (bone forming cells), and it is well recognised that the bone marrow provides the progenitor cells (mesenchymal and hematopoietic stem cells) needed for such processes to occur. Mesenchymal stem cells (MSCs) give rise to bone (including osteoblasts), adipose tissue and muscle, while the hematopoietic stem cells (HSCs) give rise to the blood cells (including osteoclasts). Many studies have attempted to investigate factors that regulate the bone remodeling process, with vitamin D as a popular choice due to its known beneficial effects in bone conditions such as osteoporosis in the elderly. Although its effect on osteoblasts, osteoclasts and myocytes are well known, the effects on the progenitor cells are not. Currently, the origin of osteoblastic cells is not as well understood as osteoclastic cells. With ageing, there is a significant reduction in the number and quality of the osteogenic precursors within the bone marrow, which is more prominent in osteoporotic bone. This has allowed researchers to hypothesise that increasing the number of osteoblast precursors in bone could be used as a new approach to osteoporosis. However, one of those potential therapeutic options involves an invasive and complex technique of bone biopsy with aspiration to obtain such progenitor cells for ex-vivo culturing and re-implantation for treatment in osteoporotic patients. This has led to the research of less invasive techniques that aim to assess the quality and quantity of such progenitor cells without the need of invasive procedures, with one such development being the discovery of circulating osteogenic progenitor (COP) cells within peripheral blood. COP cells are considered as a surrogate of MSC population in the bone marrow and are implicated in processes such as the pubertal growth spurt and frailty. Presently, there are few interventional studies regarding COP cells described in the literature. As such, more should be done in an attempt to explore and further characterise the biology of COP cells and their exact role in bone formation. In addition, COP cells could become a biomarker for diseases that affect MSC population, such as sarcopenia and osteoporosis, and also as an indicator of the therapeutic response to treatments that induce bone formation. There have been many studies recognising various compounds that affect bone. Vitamin D is one of those compounds with an anabolic effect on bone and also as an inhibitor of bone marrow adipogenesis. In this study, we hypothesise that individuals who are deficient in vitamin D will have a relatively lower number of COP cells as compared to healthy individuals. Secondly, we also hypothesise that the beneficial effect of vitamin D supplementation on human bone is associated with increasing numbers of COP cells.

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