Effects of cisplatin on parathyroid hormone- and human lung tumor-induced bone resorption.
We have previously shown that dichlorodiamine platinum (DDP), or cisplatin, a cancer chemotherapeutic agent, is effective in the treatment of malignancy-associated hypercalcemia. In the present studies, we evaluated its effects on bovine parathyroid hormone (PTH)- or tumor-induced bone resorption in vitro in the neonatal mouse calvarial bone resorption assay. PTH alone or tumor extract (TE) of a human squamous cell lung cancer alone caused a significant increase in the bone resorption and in the number of osteoclasts in the calvaria. The addition of 3 and 10 micrograms/ml DDP inhibited the PTH- or TE-induced bone resorption. Lower doses of 1 and 2 micrograms/ml DDP, although not effective in inhibiting the PTH-induced bone resorption, were effective in lowering the TE-induced bone resorption. The number of osteoclasts was also reduced by DDP treatment. We therefore conclude that DDP is effective in the treatment of malignancy-associated hypercalcemia by virtue of its inhibitory effects on osteoclast numbers and on bone resorption.
Abramson
E C
EC
University of Illinois, Chicago.
Chang
J
J
Mayer
M
M
Kukla
L J
LJ
Shevrin
D H
DH
Lad
T E
TE
Buschman
R
R
Kukreja
S C
SC
D000818:Animals; D001862:Bone Resorption / Q000187:drug effects*; D002417:Cattle; D002945:Cisplatin / Q000494:pharmacology*; D006801:Humans; D008175:Lung Neoplasms / Q000503:physiopathology*; D051379:Mice; D008854:Microscopy, Electron; D009368:Neoplasm Transplantation; D010281:Parathyroid Hormone / Q000502:physiology*
D010281:Parathyroid Hormone; D002945:Cisplatin