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1,25-Dihydroxycholecalciferol Stimulates Osteoclasts in Rat Bones in the Absence of Parathyroid Hormone^*

Department of Orthopedic Surgery, Harvard Medical School, Children's Hospital Medical Center Boston, Massachusetts 02115;
the Department of Medicine, Endocrine Unit, Harvard Medical School, Massachusetts General Hospital Boston, Massachusetts 02114

Address all correspondence and requests for reprints to: Dr. Marijke E. Holtrop, Department of Orthopaedic Surgery, Children's Hospital Medical Center, 300 Longwood Avenue, Boston, Massachusetts 02115.

Abstract

Three experiments were carried out to test the time course of effects of 1,25-dihydroxyvitamin D₃ [1,25-(OH)₂D₃] on the ultrastructural morphometry of osteoclasts. The addition of lactose to a vitamin D-deficient diet with a high calcium and phosphate content, fed to weanling rats for 4 weeks, ensured normocalcemia and normophosphatemia and allowed thyroparathyroidectomy without ill effects. In these vitamin Ddeficient thyroparathyroidectomized rats, iv injection of 50 ng 1,25-(OH)₂D₃ resulted in significant changes in the osteoclasts in the metaphysis of the tibiae compared to those in corresponding controls; the size of these cells, their nuclei, ruffled borders, and clear zones enlarged after 6 h and the number of osteoclasts increased after 48 h. Serum calcium and serum phosphate levels increased after 12 h in one experiment, but not in a second experiment. Serum 25-hydroxyvitamin D and serum immunoreactive parathyroid hormone levels were undetectable. Mineralization of metaphyseal bone matrix was normal, as quantified by histomorphometry. When, dependent on the mineral content in the diet, mineralization was impaired and the volume density of the osteoid seams was increased, activation of osteoclasts by 1,25-(OH)₂D₃ was not seen until 12–24 h after injection. It is concluded that a physiological dose of 1,25-(OH)₂D₃ stimulates the activity of osteoclasts in the absence of parathyroid hormone.

Footnotes

^* This work was supported by Grant AM-17834 from the NIH. Part of this work was presented at the Orthopedic Research Society Meeting, 1979, and the American Society for Bone and Mineral Research Meeting, 1979.

Received June 5, 1980.

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