RESORPTION WITHOUT OSTEOCLASTS (OSTEOLYSIS) 533 



One littermate without treatment was killed at the same time. 



2. Five dogs were injected twice a day with 100 miits of Para- 

 Thor-Mone ( total 600 units ) and killed on the 4th day. 



Five littermates without treatment were killed at the same time. 



3. One dog was injected with 1000 units of Para-Thor-Mone and 

 killed after 24 hours. 



One dog was injected with 1000 units of Para-Thor-Mone and 

 killed after 3 hours. 



Dogs — EDTA. Ten normal dogs maintained on the regular 

 stock diet were used. They were fasted overnight and anesthetized 

 with nembutal. Blood samples of 5 ml were taken at 30-minute 

 intervals, and the plasma was analyzed for calcium by a modifica- 

 tion of the method of Fales ( 1953 ) . After a 1-hour control period, 

 bone biopsies were taken from skull, iliac crest, and tibial shaft. 

 The dogs were then infused intravenously with an isotonic solution 

 of disodium ethylenediamine tetraacetate (EDTA) in saline which 

 had been adjusted to pH 7.4. The infusion was given at the rate of 

 40 ml per hour, and the concentration of EDTA was adjusted so 

 that 5 to 15 mg calcium were chelated and removed per hour. Since 

 the Ca-EDTA chelate is formed instantly and is physiologically 

 inert, the calcium is removed from the physiological milieu imme- 

 diately and as effectively as if it had been actually taken out of the 

 body (Copp et al., 1961). The effects produced are therefore due 

 to the resulting hypocalcemia rather than to the EDTA. A typical 

 curve showing the changes in plasma calcium and phosphorus 

 during the course of the experiment is shown in Fig. A. It should 

 be noted that the plasma calcium was determined by a method 

 which does not include the EDTA-bound calcium. The curve for 

 this animal indicates that under the stimulus of hypocalcemia and 

 increased endogenous parathormone production the dog was able 

 to more than balance the removal of 7.5 mg Ca/kg/hour or 2.2 gm 

 over a 14-hour period. After 12 hours of EDTA infusion, bone biop- 

 sies were taken from the opposite side of the body to correspond 

 to the original control samples. It was therefore possible to compare 

 bone from the same animal before and after the period of active 

 calcium mobilization. 



