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.