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Short-Term Treatment of Rats with High Dose 1,25-Dihydroxyvitamin D₃ Stimulates Bone Formation and Increases the Number of Osteoblast Precursor Cells in Bone Marrow¹

Institute of Physiology, Physiological Chemistry and Animal Nutrition (R.G.E.), Ludwig Maximilians University, 80539 Munich, Germany; University of Sheffield Medical School (A.M.S., D.M.), Sheffield, United Kingdom S10 2RX; and Schering Research Laboratories (U.K., M.H.), Schering Ltd., 13342 Berlin, Germany

Address all correspondence and requests for reprints to: Dr. Reinhold G. Erben, Institute of Animal Physiology, University of Munich, Veterinaerstrasse 13, D-80539 Munich, Germany. E-mail: R.Erben{at}lrz.uni-muenchen.de

Using an experimental rat model, this study was undertaken to assess the effects of a short-term application of high dose 1,25-dihydroxyvitamin D₃ [1,25-(OH)₂D₃] on calcium homeostasis, cancellous bone formation, and numbers of osteoblast precursors in ex vivo bone marrow cultures. For Exp 1 and 2, 6-month-old female rats were sc injected with either 0.2 µg 1,25-(OH)₂D₃/kg·day or vehicle on days 1, 2, and 3 of the studies. Serum calcium and urinary excretion of calcium were monitored for 12 days in Exp 1. In Exp 2, the rats were ip labeled with five 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 processed for histomorphometry. In Exp 3, 0.2 µg 1,25-(OH)₂D₃/kg BW or vehicle was sc administered to 6-month-old male rats on days 1, 2, and 3, and the number of colony-forming units with the ability to express alkaline phosphatase, to calcify, and/or to synthesize collagen were enumerated sequentially on days 4, 6, 8, 10, 12, and 14 in bone marrow cultures. Short-term 1,25-(OH)₂D₃ treatment resulted in increased values for serum and urinary calcium during the treatment phase in Exp 1, depressed osteoclast numbers and strongly elevated osteoblast perimeter by day 7, and stimulated mineral apposition rate and bone formation rate in the interval between days 5–15 of Exp 2. Moreover, 1,25-(OH)₂D₃ administration to rats significantly enhanced the number of mesenchymal precursor cells in bone marrow with the ability to differentiate 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)₂D₃ treatment creates new bone remodeling units and augments osteoblast recruitment and osteoblast team performance in rat cancellous bone.

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