Hypercalcemia, Excessive Bone Resorption, and Neutrophilia in Mice Bearing a Mammary Carcinoma

In an attempt to gain insight into the relationship between bone marrow and bone tissue, studies of bone metabolism and quantitative analysis of bone structure were carried out in mice following a transplantation of a granulocytosis-inducing mammary carcinoma. With the progression of the tumor growth and development of granulocytosis, there was a sharp increase in plasma calcium and urine calcium, both reaching over 200% of control values. Hypercalcemia was associated with a significant increase in urinary hydroxyproline (P < 0.005), an increase in marrow medullary area (P < 0.05), and an increase in number of endosteal osteoclasts (P < 0.005), together indicating that the cause of hypercalcemia was an increase in bone resorption. In parallel with hypercalcemia and hypercalcuria, there was an increase in urinary cyclic AMP excretion. The removal of the tumor normalized both blood neutrophil counts and plasma calcium levels, suggesting that a humoral agent from the tumor tissue, rather than tumor metastasis to bones, may be responsible for the phenomena. These studies documented the association of excessive bone resorption in this animal model of tumor-induced neutrophilia; the model may prove useful for studies of tumor-associated hypercalcemia as well as studies of marrow and bone interactions.