In vivo Morphologic Changes in the Rat Osteoclast Induced by Gallium Nitrate: The Result of Toxicity or Other Effects?Gruber H.E. · Norton H.J. · Singer F.R.
aOrthopaedic Research Laboratory, Department of Orthopaedic Surger, and bDepartment of Biostatistics, Carolinas Medical Center, Charlotte, N.C.; cJohn Wayne Cancer Institute, Santa Monica, Calif., USA
Gallium nitrate, an approved antitumor drug, has found clinical application in the treatment of cancer-related hypercalcemia and of Paget’s disease; the exact mechanism of its action, however, remains unknown. The present study utilized rats in a 7-day exposure to gallium at doses similar to those used clinically. Quantitative histomorphometry and ultrastructural examination of osteoclast fine structure were carried out on specimens from animals with documented hypocalcemia. Gallium exposure produced striking changes in the osteoclast. The number of nuclei/osteoclast increased, and the ruffled borders of the osteoclasts were markedly decreased along the length of the Howship’s lacunar cavity. The absence of a decrease in osteoclast number and the types of changes seen in ultrastructure suggest that the mechanism of action of gallium seen here may differ from that of calcitonin, a nontoxic, reversible antiresorbing agent. Results underscore the difficulty in assessing the toxicity of agents such as gallium on the osteoclast, a mature differentiated cell which does not divide and which does not produce a characteristic extracellular matrix component.
Helen E. Gruber, PhD. Senior Scientist
Orthopaedic Research Biology
Carolinas Medical Center, PO Box 32861
Carlotte, NC 28232 (USA)
Tel. +1 704/355 5658, Fax +1 704/355 2845, E‐Mail email@example.com
Number of Print Pages : 8
Number of Figures : 7, Number of Tables : 1, Number of References : 42
Mineral and Electrolyte Metabolism
Vol. 25, No. 3, Year 1999 (Cover Date: May-June 1999)
Journal Editor: Shaul G. Massry, Los Angeles, Calif.
ISSN: 0378–0392 (print), 1423–016X (Online)
For additional information: http://www.karger.com/journals/mem