SummaryThe extractions of 85 Sr 2+ , 18 F − , sucrose-14 C, EDTA-51 Cr, and antipyrine-14 C in bone were determined by the multiple indicator-dilution method. Fluoride and strontium extractions were 18 to 70% during a single transcapillary passage, and those of EDTA and sucrose were from 11 to 59%, whereas extraction of antipyrine was 87%. Injections of 85 Sr 2+ and 18 F − made when perfusion was done alternately with blood and plasma resulted in similar fractional extractions. When flow and extraction were measured simultaneously, extraction was related inversely to flow.

In a study of a standardized fracture of the tibia in dogs, we examined the relationship between extraction of strontium-85, as measured by a multiple indicator-dilution technique, and blood flow, as determined by an iodoantipyrine-washout technique. Although the blood flow at the fracture site increased from a control value of 1.5 milliliters per 100 grams of bone per minute to a value of 6.65 milliliters per 100 grams of bone per minute at two weeks, the maximum instantaneous extraction of 85 Sr by the fractured tibiae did not change from a value of about 0.77 of the amount injected. These results suggest that the increase in blood flow is accomplished by recruitment of capillaries, that the permeabilities of the capillary beds in the fractured tibia and in the normal tibia are similar, and that the pattern of flow in the fractured tibia remains non-uniform. The increased capillary surface area available for exchange is suggested as the reason that strontium extraction was unchanged despite the increased flow.Clinical Relevance-This study has shown that calcium is only moderately rapidly exchangeable across the capillary membrane and made available for uptake by osteoblasts and deposition in callus at the fracture site. Because calcium delivery via capillary is essential, and because capillary surface area is ordinarily increased in the region of a healing fracture, we can now see clearly that clinical treatment, in particular manipulative intervention, should be carried out in a fashion that minimizes damage to the capillary bed. The exchange processes described in this study are the same as those involved in the deposition of agents used for bone-scanning, and thus this information provides a basis for the timing of scanning studies and for their interpretation.The use of tracer kinetics provides an important technique for the study of the metabolic activity of tissues. Tracers that concentrate in bone, such as the isotopes 85 Sr and 47 Ca, have been helpful in examining exchange between circulating blood and bone. The quantity of tracer that enters bone must be related to the blood flow -that is, to the amount of tracer delivered to the bone -and to the diffusion of tracer through the capillary wall of the capillary tube. If bone is like other tissues, the flux of ions and solutes across the capillary wall is related to the flow of the fluid carrying the ions and solutes, to the extraction of ions in the tissue, to the permeability of the capillary wall, and to the surface area of the capillaries.The quantity of tracer that enters bone can be expressed most simply as deposition for a given period of time. For example, if the period is ten minutes, deposition can be expressed by the formula: Dividing deposition by the time of the experiment, ten minutes, gives clearance, which has the units milliliters per gram of bone per minute, the same units as those for blood flow in bone. However, clearance may also be viewed as the minimum volume of blood entering an organ per unit of time which is capable ...

The kinetics of exchange of strontium (85Sr) and potassium (42K) were studied in the mid-tibial cortical bone of 37 adult dogs. After injection of these two tracer cations and tracer-labeled albumin into the tibial nutrient artery, two types of observations were made: 1) collection of sequential venous samples to provide the outflow indicator-dilution curves and to calculate the extraction and retention at early times; and 2) detection of energy-selected gamma emissions via a detector over the tibia to give the time course of content of 42K and 85Sr in the tibia. Extractions of K+ and Sr2+ were 50 and 60% during a single transcapillary passage. More Sr2+ than K+ was retained in the first minutes. Their rates of washout over a 3-h period were similar. The interpretation is that the rate of uptake at extravascular sites is faster for Sr2+ than for K+, as is the rate of release, and that the extravascular volume of distribution for Sr2+ (adsorption sites in the interstitium or on bone) is much larger than that for K+ (intracellular).

The exchange of calcium and strontium ions in bone was studied in control dogs, dogs made hypocalcemic by parathyroidectomy, and dogs rendered hypercalcemic by injection of parathyroid hormone. After injections of tracer into the tibial nutrient artery, extraction of tracer during transcapillary passage was measured and expressed as a fraction of 1. Extraction over the first 3 min in normal dogs was 0.46 ± 0.09 (n = 6), in hypocalcemic dogs it was increased to 0.53 ± 0.07 (n = 6), and in hypercalcemic dogs it was decreased to 0.39 ± 0.07 (n = 5). Subsequent washout was less rapid than normal in hypoparathyroid dogs and more rapid than normal in hyperparathyroid dogs. We conclude from this that the immediate volume of distribution in bone (or the number of available binding sites) for strontium diminishes as the parathyroid hormone level increases.Keywords blood flow; transport calcium tracers; parathyroid glands; ion regulation; volumes of distribution; calcium bindingThe principal objective of this study was to clarify the role that bone may play in the control of the calcium ion level in blood. Two apparently contrary positions are held: one, that calcium homeostasis is mainly under renal or gut control (16,18,20), and the other, that there is a controlling physiologic mechanism in bone for ionic transport (14,24). It is probable that both of these systems operate in parallel, but their relative importance remains unclear.In a series of in vivo studies from this laboratory (3,4,7,11,17), it has been demonstrated that the principal mechanism of exchange between blood and extravascular fluid is by passive diffusion across the capillary wall, even for Sr 2+ and Ca 2+ , which concentrate in bone. This concept is also supported by evidence of Neuman et al. (15) from in vitro experiments. However, calcium and strontium differ from other solutes in being strongly retained in bone; that is, they have a large volume of distribution. It was the purpose of this investigation to use indicator-dilution studies to estimate the retention and washout of strontium and calcium in the canine tibial bone in the control situation and during hypocalcemia and hypercalcemia. MATERIALS AND METHODSThe principal experiments were concerned with the effect that parathyroid hormone has on readily exchangeable calcium ions in bone. Preliminary validating experiments were undertaken so that the interpretation of the final experiments was accurate and justified.The studies concerned the early phases of exchange, using the multiple indicator-dilution technique in two ways: first, to use the venous outflow curves to reveal the kinetics of rapid exchange with high resolution and then to use the residue curves (obtained by external gamma detection) for observing retention and rate of washout over the first hours after injection. Primary ExperimentsThese experiments concerned the effect of parathyroid state on the rapid exchange of strontium. Three groups of dogs were studied: six normal dogs, six dogs made hypocalcemic by parathyroidec...