why does radium accumulate in bones?

At the low exposures that occur environmentally and occupationally, exposure to radium isotopes causes only a small contribution to overall mortality and would not be expected to perturb mortality sufficiently to distort the normal mortality statistics. Schlenker, R. A., and J. E. Farnham. The collective volume of one set of ethmoid air cells is about 3.5 cm3; there are nine cells on the average,92 for an average volume per cell of 0.4 cm3. Committee on the Biological Effects of Ionizing Radiations (BEIR). Therefore, calculations of the uncertainty of risk estimates from the standard deviation will be accurate above 25 Ci but may be quite inaccurate and too small below 25 Ci. In an earlier summary for 24 224Ra-induced osteosarcomas,90 21% occurred in the axial skeleton. i There is little evidence for an age or sex dependence of the cancer risk from radium isotopes, provided that the age dependence of dose that accompanies changes in body and tissue masses is taken into account. Most of the points lie above the model curve for the first 12 days because no correction for fecal delay has (more). 1976. The principal factors that have been considered are the nonuniformity of deposition within bone and its implications for cancer induction and the implications for fibrotic tissue adjacent to bone surfaces. An analysis of the tumor appearance time data for carcinomas based on hazard plotting has been as employed by Groer and Marshall20 to analyze bone tumor rate in persons exposed to high doses from radium. Forms with positive coefficients, which were rejected on the basis of goodness of fit, were C + D and C + D2. An internally deposited radioactive element may concentrate in, and thus irradiate, certain organs more than others. Within the same group, four carcinomas occurred with appearance times equal to or greater than 30 yr. Calcium can accumulate in the arterial plaque that develops after an injury to the vessel wall. Among these are the injected activity, injected activity normalized to body weight, estimated systemic intake, body burden, estimated maximal body burden, absorbed dose to the skeleton, time-weighted absorbed dose, and pure radium equivalent (a quantity similar to body burden used to describe mixtures of 226Ra and 228Ra). The distribution of tumor types is not likely to undergo major changes in the future; the group of 226,228Ra-exposed patients at high risk is dwindling due to the natural mortality of old age and the rate of tumor appearance among 224Ra-exposed patients has dropped to zero in recent years.46. By measuring the radium content of 50 private wells in 27 selected counties, the counties were divided into 10 low-exposure and 17 high-exposure groups. Based on Kolenkow's work,30 Evans et al.16 reported a cumulative dose of 82,000 rad to the mucous membrane at a depth of 10 m for the subject with carcinoma. When the water supplies were divided into three groups levels of 02, 25, and > 5 pCi of 226Ra per liter and the average annual age-adjusted incidence rates were examined for the period 19691978 (except for 1972), certain cancers were found to increase with increasing radium content. This duct is normally closed, and clearance By this pathway is negligible. Roughly 900 persons who were treated with Peteosthor as children or adults during the period 19461951 have been followed by Spiess and colleagues8486 for more than 30 yr and have shown a variety of effects, the best known of which is bone cancer. In simple terms, the main issue has been linear or nonlinear, threshold or nonthreshold. . For the percent of exposed persons with bone sarcomas, Mays and Lloyd44 give 0.0046% D In the model of bone tumor induction proposed by Marshall and Groer,38 however, two hits are required to cause transformation. Leukemia has been seen in the Germans exposed to 224Ra, but only at incidence rates close to those expected in unexposed populations. A third compartment, which is not a repository for radium itself but which is relevant to the induction of health effects, consists of the pneumatized portions of the skull bones, that is, the paranasal sinuses and the air cells of the temporal bone (primarily the mastoid air cells), where radon and its progeny, the gaseous decay products of radium, accumulate. This emphasizes that there is no unique way to specify the uncertainty in risk at low exposures when the shape of the dose-response curve is unknown. 's analysis, the 228Ra dose was given a weight 1.5 times that of 226Ra. The probability of survival for cells adjacent to the endosteal surface and subjected to the estimated average endosteal dose for this former radium-dial painter was extremely small. s, where D The average skeletal doses were later calculated to be 23,000 and 9,600 rad, respectively, which are rather substantial values. Insufficiency fractures are a common complication after radiation therapy and generally affect those bones under most physiologic stress and with the . With environmental radiation, in which large populations are exposed, a spectrum of ages from newborn to elderly is represented. The mastoid air cells, like the ethmoid sinuses, are groups of interconnecting air cavities located bilaterally in the left and right temporal bones. Based on their treatment of the data, Mays et al.49 made the following observation: ''We have fit a variety of dose-response relationships through our follow-up data, including linear (y = ax), linear multiplied by a protraction factor, dose-squared exponential (y = ax 's work,17 the data were plotted against the logarithm of dose so that the low-dose region was not obscured. Each isotope of radium gives rise to a series of radioactive daughter products that leads to a stable isotope of lead (Figure 4-1a and 4-1b). Environmental Research Division. Such negative values follow logically from the mathematical models used to fit the data and underscore the inaccuracy and uncertainty associated with evaluating the risk far below the range of exposures at which tumors have been observed. On average, the dose rate from airspaces was about 4 times that from bone. Taking the former choice, it is implied that the doses given at different times interact; with the latter choice it is implied that the doses act independently of one another. Mygind, N., M. Pedersen, and M. H. Nielsen. why does radium accumulate in bones? - teppeifc.com Schlenker74 examined the uncertainties in risk estimates for bone tumor induction at low intakes and found it to be much greater than would be determined from the standard deviations in fitted risk coefficients. This observation has also been made for the retention of radium and other alkaline earths in animals Marshall and Onkelix39 explained this retention in terms of the diffusion characteristics of alkaline earths in the skeleton. A common reaction to intense radiation is the development of fibrotic tissue. The radioactive half-life of 224Ra is short enough that most of the absorbed dose to target tissues is delivered while it is resident on bone surfaces, a location from which absorbed dose delivery is especially efficient. The dose is delivered continuously over the balance of a person's lifetime, with ample opportunity for the remodeling of bone tissues and the development of biological damage to modulate the dose to critical cells. The radium from this ore evidently finds its way into the groundwater supplies. Thus, most data analyses have presented cancer-risk information in terms of dose-response graphs or functions in which the dependent variable represents some measure of risk and the independent variable represents some measure of insult. This is an instance in which an extrapolation of animal data to humans has played an important role. This cohort was derived from a total of about 1,400 pre-1930 radium-dial workers who had been identified as being part of the radium-dial industry of whom 1,260 had been located and were being followed up at Argonne. While five cases of leukemia were observed among 681 adults who received an average skeletal dose of 206 rad, none were observed among 218 1 to 20-yr-olds at an average skeletal dose of 1,062 rad. The time course for development of fibrosis and whether it is a threshold phenomenon that occurs only at higher doses are unknown. Correspondingly, relatively simple and complete dose-response functions have been developed that permit numerical estimates of the lifetime risk, that is, about 2 10-2/person-Gy for bone sarcoma following well-protracted exposure. Lyman et al.35 show a significant association between leukemia incidence and the extent of groundwater contamination with radium. Schlenker74 presented a series of analyses of the 226,228Ra tumor data in the low range of intakes at which no tumors were observed but to which substantial numbers of subjects were exposed. The first attempts at quantitative dosimetry were those of Kolenkow30 who presented a detailed discussion of frontal sinus dosimetry for two subjects, one with and one without frontal sinus carcinoma. 4, Radium. Unless there is a bias in the reporting of carcinomas, it is clear that carcinomas are relatively late-appearing tumors. Because of differences in the radioactive properties of these isotopes and the properties of their daughter products, the quantity and spatial distribution of absorbed dose delivered to target cells for bone-cancer induction located at or near the endosteal bone surfaces and surfaces where bone formation is under way are different when normalized to a common reference value, the mean absorbed dose to bone tissue, or the skeleton. In the case of 224Ra, the relatively short half-life of the material permits an estimation of the dose to bone or one that is proportional to that received by the cells at risk. 1982. 224Ra, 226Ra, and 228Ra all produce bone cancer in humans and animals. However, the change was not so great as to alter the basic conclusion that the data have too little statistical strength to distinguish between various mathematical expressions for the dose-response curve. Because of its short radioactive half-life, about 90% of the 224Ra atoms that decay in bone decay while on the surfaces.40. Hindmarsh, M., M. Owen, J. Vaughan, L. F. Lamerton, and F. W. Spiers. This, plus the high level of cell death that would occur in the vicinity of forming hot spots relative to that of cell death in the vicinity of diffuse radioactivity and the increase of diffuse concentration relative to hot-spot concentration that occurs during periods of prolonged exposure led them to postulate that it is the endosteal dose from the diffuse radioactivity that is the predominant cause of osteosarcoma induction. 1980. The times to tumor appearance for bone sarcomas induced by 224Ra and 226,228Ra differ markedly. The increase of median tumor appearance time with decreasing dose rate strengthens the case for a practical threshold. Summary of virtually all available data for adult man. Spiers, F. W., H. F. Lucas, J. Rundo, and G. A. Anast. They conclude from their microscopic measurements that the average density of radium in the portions of the pubic bone studied was about 35 times as great as that in the femur shaft; this subject developed a sarcoma in the ascending and descending rami of the os pubis. The epithelium is of squamous or cuboidal type with scattered ciliated cells but no goblet cells. This suggests that competing risks exert no major influence on the analysis by Raabe et al.61,62. and those done earlier was division of the radium-exposed subjects into subpopulations defined by type of exposure, that is, radium-dial workers (mostly dial painters), those medically exposed, and others. Specific bone complications of radiation include osteopenia, growth arrest, fracture and malignancy. In a more complete series of measurements on normal persons and persons exposed to low 226,228Ra doses, Harris and Schlenker21 reported total mucosal thicknesses between 22 and 134 m, with epithelial thicknesses in the range of 3 to 14 m and lamina propria thicknesses in the range of 19 to 120 m. Among these individuals the minimum observed time to osteosarcoma appearance was 7 yr from first exposure. The third analysis was carried out by Raabe et. A more complete description of the radium-dial painter data and parallel studies with radium in laboratory animals, particularly the rat, would do much to further such efforts. Why does radium accumulate in bones?-Radium accumulates in bones because radium essentially masks itself as calcium. The outcome of the analyses of Rowland and colleagues was the same whether intake or average skeletal dose was employed, and for comparison with the work of Evans and Mays and their coworkers, analyses based on average skeletal dose will be used for illustration. For humans and some species of animals, an abundance of data is available on some of the observable quantities, but in no case have all the necessary data been collected. There is no common agreement on which measure is the most appropriate for either variable, making quantitative comparisons between different studies difficult. The rate for the control group was 1.14; the probability of such a difference occurring by chance alone was reported as 8 in 100. This argues for the interaction of doses and in the extreme case for squaring the cumulative dose. In the United States there have been at least three attempts to determine whether the populations that drink water containing elevated levels of radium had different cancer experience than populations consuming water with lower radium levels. e The type of dose used is stated for each set of data discussed. The distribution of histologic types for radium-induced tumors is compared in Table 4-2 with that reported for naturally occurring bone tumors.11 The data have been divided into two groups according to age of record for the tumor. i + Di The statistical uncertainty in the coefficient is determined principally by the variance in the high-dose data, that is, at exposure levels for which the observed number of tumors is nonzero. i PDF Health Effects of Lead Exposure Introduction - Oregon Control cities where the radium content of the public water supply contained less than 1 pCi/liter were matched for size with the study cities. Similarly, there were six leukemias in the exposed group versus five in the control group. When plotted, the model shows a nonlinear dose-response relationship for any given time after exposure. However, no mention of such cases appear in his report. Platinum and eosin, once thought to focus the uptake of 224Ra at sites of disease development, have been proven ineffective and are no longer used. Commenting on the mucosal thickness data of Ash and Raum,2 Littman et al.31 observed: "If the dimensions of the sinus walls are applicable to the radium cases, it would appear that only a relatively sparse population of epithelial cells in the submucosal glands of the paranasal sinuses would receive significant dose from alpha particles originating in bone.". Radon is known to accumulate in homes and buildings. 1957. Whether these effects magnify other skeletal problems is unknown, but issues such as these leave the threshold-nonthreshold question open to further investigation. lefty's wife in donnie brasco; Rowland, R. E., and J. H. Marshall. Three other analyses of the data relevant to the shape of the dose-response curve are noteworthy. They used the method of hazard plotting, which corrects for competing risks, and concluded that the minimum time to tumor appearance was 5.4 yr with a 95% confidence interval of 1.37.0 yr. why does radium accumulate in bones? It is clear, therefore, that a nonzero function could be fitted to these data but would have numerical values substantially less than 28%. For nonstochastic effects, apparent threshold doses vary with health endpoint. Locations of Bone Sarcomas among Persons Exposed to 224 Ra and 226,228Ra for Whom Skeletal Dose Estimates Are Available. While the report of Mays et al.50 dealt with persons injected with 224Ra between 1946 and 1950, the study of Wick et al.95 examined the consequences of lower doses as a treatment for ankylosing spondylitis and extended from 1948 to 1975. u and I The British patients that Loutit described34 also may have experienced high radiation exposures; two were radiation chemists whose radium levels were reported to fall in the range of 0.3 to 0.5 Ci, both of whom probably had many years of occupational exposure to external radiation. As suggested by Polednak's analysis,57 the reduction of median appearance time at high dose rates in the work by Raabe et al.61,62 may be caused by early deaths from competing risks. It may be some time before this group yields a clear answer to the question of radium-induced leukemia. For tumors of known histologic type, 56% are epidermoid, 34% are mucoepidermoid, and 10% are adenocarcinomas. The normally functioning sinus is ventilated; that is, its ostium or ostia are open, permitting the free exchange of gases between the sinus and nasal cavities. The extremely high radiation doses experienced by a few of the radium-dial workers were not repeated with 224Ra, so clear-cut examples of anemias following massive doses to bone marrow are lacking. The presentation and analysis of quantitative data vary from study to study, making precise intercomparisons difficult. When an excess has occurred, there exist confounding variables. Since leukemia rates are not elevated in the radium-dial worker studies, where the radium exposures ranged from near zero to many orders of magnitude greater than could be attributed to drinking water, it is difficult to understand how radium accounts for the observations in this Florida study. They conclude that the incidence of myeloid and other types of leukemia in this population is not different from the value expected naturally. Other functions can be determined that meet this 95% probability criterion. Between 1944 and 1951 it was injected in the form of Peteosthor, a preparation containing 224Ra, eosin, and colloidal platinum, primarily for the treatment of tuberculosis and ankylosing spondylitis. 1986. All five leukemias in the control group were acute forms, while three in the exposed group were chronic myeloid leukemia. Autoradiograph of bone from the distal left femur of a former radium-dial painter showing hotspots (black areas) and diffuse radioactivity (gray areas). At high radiation doses, whole-body retention is dose dependent. Carcinomas of the Paranasal Sinuses and Mastoid Air Cells among Persons Exposed to 226,228Ra and Currently Under Study at Argonne National Laboratory. Rowland et al.67 have reported the only separate analyses of paranasal sinus and mastoid carcinoma incidence. Radium-226 adheres quickly to solids and does not migrate far from its place of release. The data for juveniles and adults was separated into different dose groups, a step not taken with the life-table analysis of Mays and Spiess.45 This, in effect, frees the analysis from the assumption of a linear dose-response relationship, implicit in the Mays and Spiess analysis. Shortly thereafter, experimental animal studies and the analysis of case reports on human effects focused on the determination of tolerance doses and radiation protection guides for the control of workplace exposure. why does radium accumulate in bones? - paginaswebconcordia.com Animal data supplemented by models are required to estimate retention in the human bone surface, and human data combined with models of gas accumulation are applied to the pneumatized space compartment. Phosphorites are rocks that are made of apatite, a mineral with the formula C a X 5 ( P O X 4) X 3 ( F, C l, O H). If there were a continuous exposure of 1 rad/yr, the tumor rate would rise to an asymptotic value. As the practical concerns of radiation protection have shifted and knowledge has accumulated, there has been an evolution in the design and objectives of experimental animal studies and in the methods of collection, analysis, and presentation of human health effects data. ANL-84-103. Such cells could accumulate average doses in the range of 100300 rad, which is known to induce transformation in cell systems in vitro. 1973. Florida has substantial deposits of phosphate, and this ore contains 238U, which in turn produces 226Ra and 222Rn. This is not a trivial point since rate of loss could be greatly affected by the high radiation doses associated with hot spots. Because of internal remodeling and continual formation of haversian systems, these cells can be exposed to buried radioactive sites. When the sinus becomes unventilated due to ostial closure, the gas composition of the sinus cavity changes and slight overpressure or underpressure may occur.13 When radioactive gases (radon) are present, as with persons exposed to 226,228Ra, there is the potential for a much higher concentration of those gases in the air of the sinus when unventilated than when ventilated. PDF Radium-226 (226Ra) - Washington State Department of Health Equations for the Functions I The take and release of activity into and out of the surface compartment was studied quantitatively in animals and was found to be closely related to the time dependence of activity in the blood.65 Mathematical analysis of the relationship showed that bone surfaces behaved as a single compartment in constant exchange with the blood.37 This model for the kinetics of bone surface retention in animals was adopted for man and integrated into the ICRP model for alkaline earth metabolism, in which it became the basis for distinguishing between retention in bone volume and at bone surfaces. Hazard functions which consider the temporal appearance of tumors have shown some promise for delineating the kinetics of radium-induced bone cancers, and may provide insight into the temporal pattern of the effective dose. 1984. On the basis of minimum and median appearance times, they concluded that the appearance times do not change with dose. A similar situation exists for female breast cancer. The standard deviation for each point is shown. Radium - an overview | ScienceDirect Topics Lyman et al.35 do not claim, however, to have shown a causal relationship between leukemia incidence and radium contamination. This keeps it from accumulating inside your home. Higher doses of radium have been shown to cause effects on the blood (anemia), eyes (cataracts), teeth (broken teeth), and bones (reduced bone growth). The final report of this study by Petersen et al.56 reported on the number of ''deaths due in any way to malignant neoplasm involving bone." For each year, the cumulative incidence so obtained was divided by the average value of the mean skeletal dose for subjects within the group, in effect yielding the slope of a linear dose-response curve for the data. It should be noted, however, that the early cases of Martland were all characterized by very high radium burdens. Only the beta and gamma rays, which were of low intensity compared to the alpha rays, emitted by these radioactive materials in the adjacent bone could have reached these cells. Radium accumulates in the bones because the radium inside the blood stream is seen as calcium , so the bones absorb it which eventually leads to it breaking down the bones . Following consolidation of U.S. radium research at a single center in October 1969, the data from both studies were combined and analyzed in a series of papers by Rowland and colleagues.6669 Bone tumors and carcinomas of the paranasal sinuses and mastoid air cells were dealt with separately, epidemiological suitability classifications were dropped, incidence was redefined to account for years at risk, and dose was usually quantified in terms of a weighted sum of the total systemic intakes of 226Ra and 228Ra, although there were analyses in which mean skeletal dose was used. Based on epizootiological studies of tumor incidence among pet dogs, Schlenker73 estimated that 0.06 tumors were expected for 789 beagles from the University of Utah beagle colony injected with a variety of alpha emitters, while five tumors were observed. These were plotted against a variety of dose variables, including absorbed dose to the skeleton from 226Ra and 228Ra, pure radium equivalent, and time-weighted absorbed dose, referred to as cumulative rad years. The third patient was reported to contain 45 g of radium. 1983. Deposition (and redeposition) is not uniform and tissue reactions may alter the location of the cells and their number and radiosensitivity. He emphasized that current recommendations of the ICRP make no clear distinction between the locations of epithelial and endosteal cells and leave the impression that both cell types lie within 10 m of the bone surface; this leads to large overestimates of the dose to epithelial cells from bone.

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