Changes in blood chemistry associated with carcinoma metastatic to bone

NTEREST IN metabolic changes in bones that I are the site of metastatic cancer dates from early studies on the metabolism of normal bone, but it was not until convenient and reliable methods for the determination of phosphatase in serum and tissue were developed by Bodansky, by King and Armstrong, and by Franseen and hlcLean that satisfactory observations could be made. It was early observed that the alkaline-phosphatase activity of the serum or plasma of some patients with carcinoma metastatic to bone was greater than n o r ~ n a l , ~ ~ 7 and that such elevations were more frequent when the metastases were osteoplastic than when they were osteolytic. Although it was thus evident that there was a general correspondence between the degree of osteoplasia of metastatic lesions of bone and the magnitude of the elevation in the alkaline phosphatase of the serum, and although it had already been shown8 that there was abundant alkaline phosphatase in the tissue at the site of osteoplastic metastases, yet the studies of Woodard and Higinbotham indicated that there were numerous cases in which the correspondence was poor. Meanwhile it began to be recognized that metastatic disease of bone was sometimes associated with abnormalities in serum calcium. In 1942 Farrow and Woodard concluded that From the Division of Experimental Surgery, SloanKettering Institute, and the Biochemistry Laboratories, Memorial Center for Cancer and Allied Diseases, New York, New York. Much of the work presented in this paper was made possible by the co-operation of member3 of the Surgical Staff of Memorial. The author wishes to thank particularly the members of the Breast Service under DI. Norman Treves; the members of the Bone Service under Dr. Bradley L. Coley; and the members of the Urological Service under Dr. Willet F. Whitmore, Jr. The author is greatly indebted to Dr. George Escher, head of the Special Breast Clinic of the Hormone Chemotherapy Section of the Division of Experimental Chemotherapy, Sloan Kettering Institute, without whose assistance many of the studies on mammary carcinoma Lmuld not have been made. The author is also indebted to Miss Mary Macdonald of the Statistics Department for assistance in analyzing the material, and to the staff of the Blood Bank under Dr. Allyn B. Ley for supplying specimens of normal blood. She also wishes to thank her numerous assodates who provided normal blood. This work was aided by the Damon Runyon Memorial Fund. Received for publication, May 20, 1953. hypercalcemia might occur whenever metastatic cancer was causing rapid destruction of bone, either during the natural course of the disease or when some unsuitable type of treatment stimulated the growth of the soft-part tumor in the bone. It thus became clear that the roentgenographic appearance of metastatic lesions in bone and the presence or absence of elevations in the alkaline phosphatase and calcium of the serum are the result of the balance between two opposing processes. One of these is the destruction of the bone by the metastatic cancer growing within it. The other is the defense or reparative activity of the injured bone, one manifestation of which is the production of alkaline phosphatase. Both processes qary greatly from patient to patient or from time to time in the same patient, either spontaneously or as a result of therapy. Hence the blood chemical picture may show various combinations of abnormalities that may be very difficult to interpret. The mechanism of the destructive process is entirely unknown, and that of the reparative process is understood only in part. Nevertheless, the evaluation of the relative intensity of the two processes is of great importance clinically. In this laboratory a considerable body of observations on the blood chemistry of patients with various types of metastatic disease of bone, both before and during endocrine therapy, has been accumulated. It is felt that a tabulation of the data on untreated patients will, by showing the frequency of abnormalities in each diagnostic group, aid in interpreting the findings in individual cases. This is the subject of the present paper. A study of the changes taking place in individual patients during various types of treatment may give indirect evidence as to the nature of the pathological processes involved. It is planned to present the results of such a study in a future communication,