Reduction of hematopoietic stem cells and adaptive increase in cell cycle rate in rickets

The close but complex physiological interactions between osteogenesis and hematopoiesis during differentiation, development, and function are unclear. As vitamin D has a major role in bone metabolism and function, we have investigated the effects of vitamin D deficiency on bone marrow cellular kinetics. Using rats in vitamin D-deficient status in utero as well as in postfetal life, we have investigated changes in hematopoiesis. Total cellularity, colony-forming unit (CFU) content, and the cycled rate were determined from the axial compartment of the femoral marrow. A marked reduction in the CFU content and a corresponding increase in the cycle fraction began at 30 days of age and stabilized by 45 days of age at 4.2 +/- 0.4 CFUs per 1 X 10(5) nucleated cells in the vitamin D-deficient animals as compared with 9.4 +/- 1.6 in the control group. During the same period of time the CFU generation time decreased from 61 +/- 5 h in the normal animals to 24 +/- 6 h in the vitamin D-deficient animals. Administration of either 1,25-dihydroxyvitamin D [1,25-(OH)2D3] or 24,25-(OH)2D3 at 45 days of age on a daily basis for 7-14 days failed to correct the defect although the serum calcium and phosphate were corrected. The data indicate that factors influencing the development of bones may affect bone marrow cells as well. Vitamin D metabolites may be needed for normal development and function of marrow-colony-forming cells in utero.