Effects of bisphosphonate (pamidronate) on bone resorption resulting from metastasis of a squamous cell carcinoma: report of an autopsy case and evaluation of bone resorbing activity in an experimental animal model.
OBJECTIVE
This study evaluated the ability of bisphosphonate to prevent bone resorption induced by metastatic tumor cells.


METHODS
Autopsy specimens of a bone metastasis from a woman with a primary squamous cell carcinoma of the tongue who developed multiple osteolytic lesions and hypercalcemia and was treated with pamidronate were studied histologically, histochemically, and ultrastructurally. In an animal experiment, cultured tumor cells (1 x 10(5)) obtained from a metastatic submandibular lymph node in the same patient were injected in the left ventricle of nude mice, and a resulting metastatic bone lesion was studied histologically and histochemically.


RESULTS
In the autopsy specimens, despite the presence of many resorption lacunae on bone surface, only a few small tartrate-resistant acid phosphatase (TRAPase)-positive cells were observed, and most of them were stained weakly and detached from the bone surface. In the animal experiment, 1 of 10 animals (10%) formed osteolytic bone metastasis, and many TRAPase-positive cells were observed histochemically.


CONCLUSIONS
Biphosphonate inhibits bone resorption induced by tumor, possibly by decreasing the number of osteoclasts and inhibiting their function.
Hiraga
T
T
School of Dentistry, Niigata University, Japan.
Takada
M
M
Nakajima
T
T
Ozawa
H
H
D000135:Acid Phosphatase / Q000378:metabolism; D000368:Aged; D000818:Animals; D001859:Bone Neoplasms / Q000150:complications* / Q000556:secondary*; D001862:Bone Resorption / Q000188:drug therapy* / Q000209:etiology / Q000517:prevention & control; D002294:Carcinoma, Squamous Cell / Q000150:complications* / Q000556:secondary*; D004164:Diphosphonates / Q000494:pharmacology / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D006934:Hypercalcemia / Q000209:etiology; D007527:Isoenzymes / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D010010:Osteoclasts / Q000187:drug effects / Q000201:enzymology; D000077268:Pamidronate; D013125:Spinal Neoplasms / Q000150:complications / Q000556:secondary; D000071681:Tartrate-Resistant Acid Phosphatase; D013904:Thoracic Vertebrae / Q000473:pathology; D014062:Tongue Neoplasms / Q000473:pathology; D014407:Tumor Cells, Cultured / Q000637:transplantation
D004164:Diphosphonates; D007527:Isoenzymes; D000135:Acid Phosphatase; D000071681:Tartrate-Resistant Acid Phosphatase; D000077268:Pamidronate