Quantitative bone histomorphometry in nude mice bearing a human squamous cell lung cancer.
We performed quantitative bone histomorphometry on lumbar vertebrae in hypercalcemic tumor-bearing athymic mice carrying a human squamous cell carcinoma. For comparison, studies were also performed in athymic mice that received bovine 1-34 parathyroid hormone (PTH) infusion at the rate of 0.167 micrograms/hr for 7 days. In both the PTH-infused and tumor-bearing animals, percent cortical and total bone areas were significantly reduced as compared to controls, whereas trabecular bone was significantly reduced only in the tumor-bearing animals. Trabecular perimeter lined by osteoclasts was significantly increased in both tumor-bearing (1.7-fold) and PTH-infused animals (2.8-fold) compared to control mice. Trabecular perimeter lined by active osteoblasts was significantly reduced in the tumor-bearing animals (to 42% of control) and unchanged in the PTH-infused animals (97% of control). Tumor-bearing animals had significantly reduced resorptive as well as formative surfaces as compared to the PTH-infused animals. Dynamic histomorphometry revealed a marked reduction in bone formation rate (23% of control) in the tumor-bearing animals. The studies therefore demonstrate a marked inhibition of bone formation associated with increased bone resorption in this model of hypercalcemia of malignancy. These observations are similar to those seen in the human syndrome.
Kukreja
S C
SC
VA West Side Medical Center, Chicago, IL.
Rosol
T J
TJ
Shevrin
D H
DH
York
P A
PA
D000818:Animals; D001862:Bone Resorption / Q000187:drug effects; D001842:Bone and Bones / Q000187:drug effects / Q000473:pathology*; D002294:Carcinoma, Squamous Cell / Q000473:pathology*; D006801:Humans; D008175:Lung Neoplasms / Q000473:pathology*; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D010011:Osteocytes / Q000166:cytology / Q000187:drug effects; D010281:Parathyroid Hormone / Q000494:pharmacology; D010446:Peptide Fragments / Q000494:pharmacology; D012016:Reference Values; D019379:Teriparatide; D014183:Transplantation, Heterologous
D010281:Parathyroid Hormone; D010446:Peptide Fragments; D019379:Teriparatide