Osteoporosis‐like Changes in Walker Carcinoma 256‐Bearing Rats, Not Accompanied with Hypercalcemia or Parathyroid Hormone‐related Protein Production

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Abstract
Walker carcinoma 256 (W256) was reported to induce hypercalcemia dependent on bone metastasis and/or parathyroid hormone‐related protein (PTHrP) in the rat, providing a model of the humoral hypercalcemia of malignancy. In this study, after the subcutaneous inoculation of cells of the W256/S line, which is maintained in this laboratory, into young female Wistar Imamichi rats (6 weeks old), serum calcium and phosphorus levels changed only within the control range, whereas serum alkaline phosphatase activity and urinary calcium level significantly increased and urinary phosphorus decreased during the tumor growth, resulting in hypercalciuria and hypophosphaturia. W256/S did not express PTHrP‐mRNA, whereas LLC‐W256 cells did express it. Serum PTHrP level was not changed in W256/S‐bearing rats. Osteoporosis‐like changes, bone weight loss, low contents of bone calcium and phosphorus, and a decrease in the bone mineral density (BMD), were observed in the femur 14 days after the tumor inoculation. There was a pronounced decrease in the serum 17β‐estradiol level during the tumor growth. The reduction of BMD of femurs in W256/S‐bearing rats was significantly inhibited by treatment with salmon calcitonin or 17β‐estradiol. On the basis of these results, W256/S carcinoma‐bearing rats seem to be a useful model for osteoporosis of hypoovarianism.