SHORT-TERM TREATMENT OF RATS WITH HIGH-DOSE 1,25-DIHYDROXYVITAMIN D-3STIMULATES BONE-FORMATION AND INCREASES THE NUMBER OF OSTEOBLAST PRECURSOR CELLS IN BONE-MARROW

Using an experimental rat model, this study was undertaken to assess t he effects of a short-term application of high dose 1,25-dihydroxyvita min D-3 [1,25-(OH)(2)D-3] on calcium homeostasis, cancellous bone form ation, and numbers of osteoblast precursors in ex vivo bone marrow cul tures. For Exp 1 and 2, 6-month-old female rats ware sc injected with either 0.2 mu g 1,25-(OH)(2)D-3/kg.day or vehicle on days 1, 2, and 3 of the studies. Serum calcium and urinary excretion of calcium were mo nitored for 12 days in Exp 1. In Exp 2 the rats were ip labeled with f ive different fluorochromes on days 0, 5, 10, 15, and 20, respectively . Half of the rats in each group were killed on day 7, the rest of the rats were killed on day 24, and the first lumbar vertebrae were proce ssed for histomorphometry. In Exp 3, 0.2 mu g 1,25-(OH)(2)D-3/kg BW or vehicle was sc administered to 6-month-old male rats on days 1, 2, an d 3, and the number of colony-forming units with the ability to expres s alkaline phosphatase, to calcify, and/or to synthesize collagen were enumerated sequentially on days 4, 6, 8, 10, 12, and 14 in bone marro w cultures. Short-term 1,25-(OH)(2)D-3 treatment resulted in increased values for serum and urinary calcium during the treatment phase in Ex p 1, depressed osteoclast numbers and strongly elevated osteoblast per imeter by day 7, and stimulated mineral apposition rate and bone forma tion rate in the interval between days 5-15 of Exp 2. Moreover, 1,25-( OH)(2)D-3 administration to rats significantly enhanced the number of mesenchymal precursor cells in bone marrow with the ability to differe ntiate into an osteoblastic phenotype in ex vivo bone marrow cultures on day 4 of Exp 3. These studies provide evidence that short-term 1,25 -(OH)(2)D-3 treatment creates new bone remodeling units and augments o steoblast recruitment and osteoblast team performance in rat cancellou s bone.