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The effect of low calcium diet, mithramycin, and dichlorodimethylene bisphosphonate on humoral hypercalcemia of malignancy in nude mice transplanted with the canine adenocarcinoma tumor line (CAC‐8)
Author(s) -
Rosol T.J.,
Capen C.C.
Publication year - 1987
Publication title -
journal of bone and mineral research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.882
H-Index - 241
eISSN - 1523-4681
pISSN - 0884-0431
DOI - 10.1002/jbmr.5650020506
Subject(s) - endocrinology , calcium , bisphosphonate , bone resorption , medicine , chemistry , bone remodeling , nude mouse , excretion , urinary calcium , urine , tartrate resistant acid phosphatase , hypercalciuria , osteoporosis , osteoclast , cancer , receptor
The effect of a low calcium diet, mithramycin, or dichlorodimethylene bisphosphonate were evaluated in nude mice with humoral hypercalcemia of malignancy associated with the transplanted canine adenocarcinoma (CAC‐8). Low calcium (0.01%) diet significantly reduced serum calcium levels in hypercalcemic nude mice and reduced urine calcium excretion to control levels. Mithramycin (8 mg/kg) decreased serum calcium concentration and urine calcium excretion to the range of control non‐tumor‐bearing nude mice at day 5 after a single injection, but there was no change in the number of tartrate‐resistant acid phosphatase‐positive osteoclasts in lumbar vertebrae. Osteoclasts from CAC 8‐bearing nude mice after mithramycin administration were decreased in size, had small ruffled borders, and increased relative size of clear zones. Dichlorodimethylene bisphosphonate (Cl 2 MDP) (45 mg/kg) partially reduced serum calcium concentration of hypercalcemic tumor‐bearing nude mice, decreased urine calcium excretion to control levels, and markedly reduced the numbers of tartrate‐resistant acid phosphatase‐positive osteoclasts in lumbar vertebrae. Osteoclasts from Cl 2 MDP‐treated nude mice were smaller and had a reduced frequency of ruffled borders than saline‐treated hypercalcemic nude mice. In vitro bone resorption induced by CAC‐8 extract was significantly reduced by C1 2 MDP and mithramycin. The results of these investigations suggest that the hypercalcemia and hypercalciuria associated with HHM in nude mice with CAC‐8 are the combined result of altered calcium homeostasis in the bone, kidney, and intestine. Chemotherapeutic agents that specifically affect only bone or feeding a low calcium diet alone may not completely ameliorate the hypercalcemia of HHM.