why does radium accumulate in bones? why does radium accumulate in bones?

Schumacher, G. H., H. J. Heyne, and R. Fanghnel. 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. Cumulative incidence, computed as the product of survival probabilities in the life table,10 was used as the measure of response with errors based on approximations by Stehney. For continuous intake with the dose-squared exponential function for bone sarcoma induction, it is necessary to decide whether to add the cumulative dose and then take the square or to take the square for each annual increment of dose. Whether due to competing risks, dose protraction, or a combination, it is clear that differential radiosensitivity for this group of subjects is a hypothesis that cannot be supported. The weight of available evidence suggests that bone sarcomas arise from cells that accumulate their dose while within an alpha-particle range. Nevertheless, the discussion of leukemia as a possible consequence of radium exposure has appeared in a number of published reports. As an example, the upper boundaries of the 95% confidence envelope for total cumulative incidence corrected for competing risks are: Dose-response envelopes for 224Ra from equation 416. There were 11 bone marrow failures in the exposed group, and only 4 in the control group. i). l, respectively) of an envelope of curves that provided acceptable fits to the data, as judged by a chi-squared criterion. 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. As with 226,228Ra, the curves in Figure 4-8 can be used to establish confidence limits for risk estimates at low doses, although it is to be understood that these limits are not unique, because the shape of the dose-response curve is unknown. Rowland, R. E., A. F. Stehney, and H. F. Lucas, Jr. If the survival adjacent to the diffuse component were 37%, as might occur for endosteal doses of 50 to 150 rad, the hot-spot survival would be 0.09%. Whether these effects magnify other skeletal problems is unknown, but issues such as these leave the threshold-nonthreshold question open to further investigation. 2)exp(-1.1 10-3 The kinetics of radon accumulation in the pneumatized air spaces are determined by the kinetics of radium in the surrounding bone, the rate of diffusion from bone through the intervening tissue to the air cavity, and the rate of clearance through the ventilatory ducts and the circulatory system. Data points fall along a straight line when the tumor rate is constant. Therefore, the minimum observed tumor appearance time is not an absolute lower bound, and there is a small nonzero chance for tumors to occur at doses less than the practical threshold. Among these individuals the minimum observed time to osteosarcoma appearance was 7 yr from first exposure. Included in the above summary are four cases of chronic lymphocytic or chronic lymphatic leukemia. When these ducts are open, clearance is almost exclusively through them. In a more complete development, Schlenker73 investigated the dosimetry of sinus and mastoid epithelia when 226Ra or 228Ra was present in the body. Carcinomas of the frontal sinus and the tympanic bulla, a portion of the skull comparable to the mastoid region in humans, have appeared in beagles injected with radium isotopes and actinides. Other functions can be determined that meet this 95% probability criterion. The theory of bone-cancer induction by alpha particles38 offers some insights. i are as defined above. 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. Thurman, G. B., C. W. Mays, G. N. Taylor, A. T. Keane, and H. A. Sissons. As indicated in Annex 7A, the radium-dial painter data can be a useful source of information for extrapolating to man the risks from transuranic elements that have been observed in animal studies. The relative frequencies for fibrosarcomas induced by 224Ra and 226,228 Ra are also different, as are the relative frequencies for chondrosarcomas induced by 226,228Ra and naturally occurring chondrosarcomas. When the model is used for radium, careful attention should be paid to the constraints placed on the model by data on radium retention in human soft tissues.74 Because of the mathematical complexity of the retention functions, some investigators have fitted simpler functions to the ICRP model. The first case of bone sarcoma associated with 226,228Ra exposure was a tumor of the scapula reported in 1929, 2 yr after diagnosis in a woman who had earlier worked as a radium-dial painter.42 Bone tumors among children injected with 224Ra for therapeutic purposes were reported in 1962 among persons treated between 1946 and 1951.87. Recent analyses with a proportional hazards model led to a modification of the statement about the adequacy of the linear curve, as will be discussed later. The analysis shows that the minimum appearance time varies irregularly with intake (or dose) and that the rate of tumor occurrence increases sharply at about 38 yr after first exposure for intakes of greater than 470 Ci and may increase at about 48 yr after first exposure for intakes of less than 260 Ci. Because of its preference for bone, radium is commonly referred to as a bone seeker. Radium . A single function was fitted to these data to describe the change of the dose-response curve slope with the length of time over which injections were given: where y is the number of bone sarcomas per million person-rad and x is the length of the injection span, in months. If this reduction factor applied to the entire period when 224Ra was resident on bone surfaces and was applicable to humans, it would imply that estimates of the risk per unit endosteal dose, such as those presented in the Biological Effects of Ionizing Radiation (BEIR) III report,54 were low by a factor of 23. 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. Hindmarsh, M., M. Owen, and J. Vaughan. The average skeletal doses were later calculated to be 23,000 and 9,600 rad, respectively, which are rather substantial values. The analysis was not carried out for carcinoma risk, but the conclusions would be the same. Environmental Research Division. Two compartments are usually identified in the skeleton, a bone surface compartment in which the radium is retained for short periods and a bone volume compartment in which it is retained for long periods. Hasterlik, R. J., L. J. Lawson, and A. J. Finkel. For animals given a single injection, hot spots probably played a role similar to that played by diffuse radioactivity. When the size of the study group was reduced by changing the criterion for acceptance into the group from year of first entry into the industry to year of first measurement of body radioactivity while living, the observed number of bone tumors dropped from 42 to 13, because radioactivity in many persons was first measured after death. In summary, hot spots may not have played a role in the induction of bone cancer among members of the radium population under study at Argonne National Laboratory because of excessive cell killing in tissues which they irradiate, and the carcinogenic portion of the average endosteal dose may have been about one-half of the total average endosteal dose. Raabe, O. G., S. A. Schlenker, R. A., and B. G. Oltman. The primary sources of information on the health effects and dosimetry of radium isotopes come from extensive studies of 224Ra, 226Ra, and 228Ra in humans and experimental animals. i i = 0.5 Ci, the lower boundary of the lowest intake cohort used when fitting functions to the data. how long is chickpea pasta good for in the fridge. All of these cases occurred among 293 women employed in Illinois; none were recorded among the employees from radium-dial plants in other states. old trucks for sale by owner'' in ontario; Some 55 sarcomas of bone have occurred in 53 of 898 224Ra-exposed patients whose health status is evaluated triennially.46 Two primary sarcomas occurred in 2 subjects. These constitute about 85% of the subjects with bone sarcoma on which the most recent analyses have been based. Many of the 2,403 subjects are still alive. 16/06/2022 . This report indicates that the age- and sex-adjusted osteosarcoma mortality rate for the total white population in the communities receiving elevated levels of radium for the period 19501962 was 6.2/million/yr; that of the control population was 5.5. A comparison study included 1,185 women employed between 1930 and 1949, when radium contamination was considerably lower. If radium is ingested or inhaled, the radiation emitted by the radionuclide can interact with cells and damage them. A., P. Isaacson, W. J. Hausler, and J. Kohler. The paranasal sinuses are cavities in the cranial bones that exchange air and mucus with the nasal cavity through a small ostium. Direct observations of the lamina propria indicate that the thickness lies between 14 and 541 m.21. For this reason, diffuse radioactivity may have been the primary cause of tumor induction among those subjects in whom bone cancer is known to have developed. Autoradiograph of bone from the distal left femur of a former radium-dial painter showing hotspots (black areas) and diffuse radioactivity (gray areas). The times to tumor appearance for bone sarcomas induced by 224Ra and 226,228Ra differ markedly. They also presented an equation for depth dose from radon and its daughters in the airspace for the case of a well-ventilated sinus, in which the radon concentration was equal to the radon concentration in exhaled breath. With life-long continuous intake of dietary radium, the distinction between hot spot and diffuse activity concentrations is diminished; if dietary intake maintains a constant radium specific activity in the blood, the distinction should disappear altogether because blood and bone will always be in equilibrium with one another, yielding a uniform radium specific activity throughout the entire mineralized skeleton. If Lloyd and Henning33 are correct, current estimates of endosteal dose for 226Ra and 228Ra obtained by calculating the dose to a 10-m-thick layer over the entire time between first exposure and death may bear little relationship to the tumor-induction process. Some of these complications, such as osteopenia, are reversible and severity is dose dependent. For male bladder cancer only, the highest radium level produced a higher cancer rate than was observed for those consuming surface water. The advantage of using a tabular form for the calculation of the effect of radiation is that it provides a general procedure that can be applied to more complex problems than the one illustrated above. The total numbers of tumors available are too small to assign significance to the small differences in relative frequencies for a given histologic type. why does radium accumulate in bones? s is 226Ra skeletal dose. 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. Radium-induced carcinomas in the temporal bone are always assigned to the mastoid air cells, but the petrous air cells cannot be logically excluded as a site of origin. Rowland et al.67 performed a dose-response analysis of the carcinoma data in which the rate of tumor occurrence (carcinomas per person-year at risk) was determined as a function of radium intake. They based their selection on the point of intersection between the line representing the human lifetime and "a cancer risk that occurs three geometric standard deviations earlier than the median." Because all of the data analysis for 224Ra has been based on prescription of dose given by Spiess and Mays,85 it is important that it be followed in applications of 224Ra dose-response relationships for the estimation of cancer risk in the general population or in case of occupational or therapeutic exposure. The higher blood flow cert. As documented above, research on radium and its effects has been extensive. 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. Deposition (and redeposition) is not uniform and tissue reactions may alter the location of the cells and their number and radiosensitivity. The excess death rate due to bone cancer for t > 5 yr is computed from: Effect of Single Skeletal Dose of 1 rad from 224Ra Received by 1,000,000 U.S. White Males at Age 40. A similar issue exists for 226Ra and 228Ra. 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. Current efforts focus on the determination of risk, as a function of time and exposure, with emphasis on the low exposure levels where there is the greatest quantitative uncertainty. The analysis of response as a function of 226Ra dose was conducted with exhumed cases included. The shaded region emphasizes that standard errors obtained by least-square fitting underestimate the uncertainty in risk at low doses. When injected into humans for therapeutic purposes or into experimental animals, radium is normally in the form of a solution of radium chloride or some other readily soluble ionic compound. Groer and Marshall20 estimated the minimum time for osteosarcoma appearance in persons exposed to high doses of 226Ra and 228Ra. The sinus ducts are normally open but can Be plugged by mucus or the swelling of mucosal tissues during illness. 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.". Polednak cautioned that the shorter median appearance time at high doses might simply reflect the shorter overall median survival time. A three- or four-inch pipe pulls radon from underneath the house and vents it outside. In the latter analysis,69 the only acceptable fit based on year of entry into the study is: where I and D The fundamental reason for this is the chemical similarity between calcium and radium. 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. 1976. Simple prescriptions for the skeletal dose from 224Ra as a function of injection level have been given by Spiess and Mays85 and can be used to estimate skeletal dose from estimated systemic intake. Sarcomas of the bones and joints comprise only 0.24% of microscopically confirmed malignancies reported by the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) program.52 The chance of contracting bone sarcoma during a lifetime is less than 0.1%. The age structure of the population at risk and competing causes of death should be taken into account in risk estimation. why does radium accumulate in bones? The distance across a typical air cell is 0.2 cm,73 equivalent to a volume of about 0.004 cm3 if the cell were spherical. D Evans15 listed possible consequences of radium acquisition, which included leukemia and anemia. Specific bone complications of radiation include osteopenia, growth arrest, fracture and malignancy. Published by at 16 de junio de 2022. The complexity of the problem is illustrated by their findings for Chicago. 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. The purpose of this chapter is to review the information on cancer induced by these three isotopes in humans and estimate the risks associated with their internal deposition. The radium content in the bodies of 185 of these workers was measured. Spiess, H., H. Poppe, and H. Schoen. There were three cases of chronic myeloid leukemia (CML) and one of chronic lymphocytic leukemia (CLL). Working from various radium-exposed patient data bases, several authors have observed that carcinomas of the paranasal sinuses and mastoid air cells begin to occur later than bone tumors.16,18,66,71 In the latest tabulation of tumor cases,1 the first bone tumor appeared 5 yr after first exposure, and the first carcinoma of the paranasal sinuses or mastoid air cells appeared 19 yr after first exposure; among persons for whom there was an estimate of skeletal radiation dose, the first tumors appeared at 7 and 19 yr, respectively. These high ratios emphasize, in quantitative terms, our ignorance of risk at low exposure levels. The increase of median tumor appearance time with decreasing dose rate strengthens the case for a practical threshold. Nevertheless, the time that bone and adjacent tissues were irradiated was quite short in comparison to the irradiation following incorporation of 226Ra and 228Ra by radium-dial workers. These estimates are based on retention integrals74 and relative distribution factors40 that originate from retention and dosimetry models. Cancer Incidence Rate among Persons Exposed to Different Concentrations of Radium in Drinking Water. There were 1,501 exposed cases and 1,556 ankylosing spondylitis controls. The linear functions obtained by Rowland et al.67 were: where D D Roughly 20% of the total lifetime endosteal dose deposited by 226Ra and its daughters is contributed by the initial surface deposit. 1966. 1:43 pm junio 7, 2022. raquel gonzalez height. The higher values of the ratios were associated with shorter exposure times, usually the order of a year or less. The ethmoid sinuses form several groups of interconnecting air cells, on either side of the midline, that vary in number and size between individuals.92 The sinus surfaces are lined with a mucous membrane that is contiguous with the nasal mucosa and consists of a connective tissue layer attached to bone along its lower margin and to a layer of epithelium along its upper margin. 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.