The effect of vitamin D supplementation on circulating osteoprogenitor cells: A pilot randomized controlled trial

Circulating osteoprogenitor (COP) cells are a relatively newly discovered mesenchymal precursors population in the peripheral blood. While some aspects of their physiology have been documented in vitro, little is known about their behavior in vivo. To facilitate understanding regarding their potential role in the management of musculoskeletal disease, more research into how these cells respond to growth factors and hormones in vivo is still required. To this end, we performed a randomized controlled pilot study investigating the effect of vitamin D supplementation on COP cells in healthy older adults. Twenty-two individuals were recruited and stratified through their baseline vitamin D levels into deficient (<35 nmol/L), insufficient (35-49 nmol/L) and sufficient (>50 nmol/L) groups, and then randomized to receive either a 50,000 IU bolus dose of vitamin D, along with a 1000 IU daily supplement for six weeks, or the 1000 IU supplement alone. Participants were assessed at baseline, week three, and week six, with the primary outcome being a change in the number of COP cells. Secondary outcomes were vitamin D, markers of bone formation and resorption, parathyroid hormone, and calcium. The study showed that, independently of the dosing, increasing vitamin D levels led to a concomitant 52% increase in COP cell number (p < 0.001). There were no differences between strata, or any of the secondary outcomes in the trial. This suggests that COP cells are regulated in some way by vitamin D, similar to the bone marrow mesenchymal stem cell. Future studies are needed to evaluate the long-term effects of vitamin D supplementation, and how COP cells may be involved in chronic musculoskeletal disease.