64 DETAILED UPTAKE OF ACTIVITY IN FORMING HAVERSIAN SYSTEMS ance, 7k, values of which are available for the earth elements in man and many animals. Continuous or Multiple Injection Single Injection Several experiments have verified that the deposition Tetracycline labeling in dogs and cats’ of alkaline earth activity in forming haversian systems occurs at the specific activity of the blood plasma at the time of that formation. Therefore, a knowledge of the average speeifie activity of the plasma during the period of tracer intake yields the specific activity of the new bone formed during the same period. An observed ratio has been used for this estimate heretofore, but the observed ratio method does not take into account the dilution of the blood plasma with unlabeled calcium transferring from bone to blood for a considerable period of time after the start of the continuous tracer intake. Furthermore, the observed ratio method is not intimately connected with the mechanisms of calcium transfer to and from the blood plasma, since It is expressed as a product of discrimination factors for urine, feces, and bone— mechanisms which in fact are tn parallel, not in series. A more powerful method for this particular calculation follows from the excretion postulate (basic postulate 1{d) above, and postulate I of Reference 5). If you Know the shape of the retention curve R for a radioisotope in the bodyfollowing a single injection, : . together with the rate of excretory plasma clearance, following a single injection, then you can derive that for: plasma specific activity following the start of continuous tracer intake simply by taking the time integral of the single injection curve. This procedure vields the simple result that the specific activity of the plasma under continuous tracer intake is So = (G/nk) (1 —_ R;), (3) where ¢ = the rate of tracer introduction into the blood nk = the rate of excretory plasma clearance in grams of calcium per day (equivalent) S,. = the plasma specific activity at any time { after the start of the continuous tracer intake ae Ei he a be oF ee E a ees eae and the specifie activity of bone formed at this time R, = the whole-body retention of the tracer at the same time ¢ after a single injection. This useful result depends only upon the excretion postulate and upon the assumption of a steady state over a relatively short period of time. It is well verified by experiment. This equilibrium value of S, for a given g depends only upontherate of excretory plasmaclear- (7-9) a labeling in a dog’” have shownthat haversian in the process of their formation lay down b: linear apposition rate that decreases in prop« the current size of the haversian canal. To a : proximation this maybe expressed dr/dt = — Br, where 7 is the radius of the canal as a function and @ is the fractional rate of closure in unitsof( Marshall found 8 = 0.03 + 0.01 day™ in anac Lee found @ values of 0.04, 0.03, and 0.026 « dogs of age 3 months, 1 year, and >1 year. tively. Manson and Waters in experiments « and cats found that the data on osteon grow well represented by ‘y= kro ; where 7; is the radius of the first label and 72 1s th of the second label. Expression (5) is consistent with expressi because the solution of (4) yields then the curve of the plasma specific activity versus time is given by the time derivative of this function nk. If you knowthe curve of plasma specific activity : To = reo, where ty» is the time interval between the la: follows that k= eae, Manson and Waters found 8 values of 0.044 an dayin cats of age 9 months and 2.5 years, respe and 8 values of 0.055 and 0.045 day~ in two adu! These expressions imply that the individual blast lays down bone more rapidly in the early of osteon formation when the canal is large | does in later stages as the canal closes. In ad there is the fact that the canal surface and, th« the number of osteoblasts decrease in direet pro] to canal radius so that the mass of bone being lak per unit of time decreases as the square of the The amount of ealeium being laid down in a fi haversian system per unit length as a function « is then _ d(Area) ff, a") g = Pa p (zr ’ where g = gramsof calcium per day per cm length 01 r p radius of canal as a function of time * 3 grams calcium per em’ of newbone.