The expected number, however, is only 1.31. why does radium accumulate in bones? None of these findings are in agreement with the long-term studies of higher levels of radium in the radium-dial workers. This ratio increases monotonically with decreasing intake, from a value of 1.5 at D 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 eustachian tube provides ventilation for the middle ear and pneumatized portions of the temporal bone. Radium-223 is a "calcium mimetic" that, like calcium, accumulates preferentially in areas of bone that are undergoing increased turnover, such as areas . Radon is known to accumulate in homes and buildings. With the analyses presently available, only part of this prescription can be achieved. Being an -emitting radionuclide, the radium irradiates bone surface-lining cells and has resulted in an excess incidence of osteogenic sarcomas. Radium concentrations in food and air are very low. why does radium accumulate in bones? 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. With 228Ra, dose delivery is practically all from bone volume, but the ranges of the alpha particles from this decay series exceed those from the 226Ra decay series, allowing 228Ra to go deeper into the bone marrow and, possibly, to irradiate a larger number of target cells. This is an instance in which an extrapolation of animal data to humans has played an important role. 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. This latent period must be included when the equations are applied to risk estimation. particularly lung and bone cancer. 1986. In this expression, C is the natural carcinoma rate and D is the systemic intake or mean skeletal dose. Whether the practical threshold represents a dose below which the tumor risk is zero, or merely tiny, depends on whether the minimum tumor appearance time is an absolute boundary below which no tumors can occur or merely an apparent boundary below which no tumors have been observed to occur in the population of about 2,500 people for whom radium doses are known. An ideal circumstance would be to know the dose-response relationships in the absence of competing causes of death and to combine this with information on age structure and age-specific mortality for the population at large. 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. Among these individuals the minimum observed time to osteosarcoma appearance was 7 yr from first exposure. For 226Ra and 228Ra the constant tumor rates given by Rowland et al.68 as functions of systemic intake are computed for the intake of interest, and the results are worked out with a table such as Table 4-7. It may be some time before this group yields a clear answer to the question of radium-induced leukemia. 1985. The points with their standard errors result from the proportional hazards analysis of Chemelevsky et al.9. For exposure at environmental levels, the distinction between hot spots and diffuse radioactivity is reduced or removed altogether. 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. For comparison with the values given previously for juveniles and adults separately, this is 2.0% incidence per 100 rad, which is somewhat higher than either of the previous values. 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. However, calcium is ubiquitous in the human body, so small amounts of radium may accumulate in other tissues, causing toxicity. Rundo, J., A. T. Keane, and M. A. Essling. Littman et al.31 have presented a list of symptoms in tabular form gleaned from a study of the medical records of 32 subjects who developed carcinoma of the paranasal sinuses or mastoid air cells following exposure to 226,228Ra. The heavy curve represents the new model. This will extend the zone of irradiation out into the marrow, beyond the region that is within alpha particle range from bone surfaces. The above results, based on observations of several thousand individuals over periods now ranging well over 50 yr, make the recent report by Lyman et al.35 on an association between radium in the groundwater of Florida and the occurrence of leukemia very difficult to evaluate. The authors concluded that bone tumors most likely arise from cells that are separated from the bone surface by fibrotic tissue and that have invaded the area at long times after the radium was acquired. Effects of radiation on bone - PubMed Malignancies of the auditory tube, middle ear, and mastoid air cells (ICD 160.1) make up only 0.0085% of all malignancies reported by the National Cancer Institute's SEER program.52 Those of the ethmoid (ICD 160.3), frontal (ICD 160.4), and sphenoid (ICD 160.5) sinuses together make up 0.02% of all malignancies, or if the nonspecific classifications, other (ICD 160.8) and accessory sinus, unspecified (ICD 160.9), are added as though all tumors in these groups had occurred in the ethmoid, frontal, or sphenoid sinuses, the incidence would be increased only to 0.03% of all malignancies. The difference between mucosal and epithelial thickness gives the thickness of the lamina propria a quantity of importance for dosimetry. Pool, R. R., J. P. Morgan, N. J. One tumor located in the left sacroiliac joint has been assigned half to the appendicular skeleton and half to the axial skeleton. u - 0.7 10-5) and (I Mays et al.50 reported on the follow-up of 899 children and adults who received weekly or twice-weekly intravenous injections of 224Ra, mainly for the treatment of tuberculosis and ankylosing spondylitis. Before concern developed over environmental exposure, attention was devoted primarily to exposure in the workplace, where the potential exists for the accidental uptake of radium at levels known to be harmful to a significant fraction of exposed individuals. The majority of the leukemias were acute myeloid leukemias. . 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. With a lifetime natural tumor risk of 0.1%, the radiogenic risk would be -0.0977%. 1962. National Research Council, In addition, blood vessel cells themselves sometimes convert into bone-forming osteoblasts, producing extra calcium on the spot. Therefore, estimates of the cumulative average skeletal dose may not be adequate to quantitate the biological insult. D As of December 1982, the average followup time was 16 yr for patients injected after 1951 with lower doses of 224Ra for the treatment of ankylosing spondylitis.93 Of 1,426 patients who had been traced, the vital status for 1,095 of them was known. The term practical threshold was introduced into the radium literature by Evans,15 who perceived an increase of the minimum tumor appearance time with decreasing residual radium body burden and later with decreasing average skeletal dose.16 A plot showing tumor appearance time versus average skeletal dose conveys the impression that the minimum tumor appearance time increases with decreasing dose. Radium has an affinity for hard tissue because of its chemical similarity to calcium. Since then it has been used with adults as a clinically successful treatment for the debilitating pain of ankylosing spondylitis. The authors drew no conclusions as to whether the leukemias observed were due to 224Ra, to other drugs used to treat the disease, or were unrelated to either. analysis, 226Ra and 228Ra dose contributions were weighted equally; in Rowland et al. 1976. Unless bone cancer induced by 226Ra and 228Ra is a pure, single-hit phenomenon, some interaction of dose increments is expected, although perhaps it is a less strong interaction than is consistent with squaring the total accumulated intake when intake is continuous. Thus, the spectrum of tumor types appears to be shifted from the naturally occurring spectrum when the tumors are induced by radium. Source: Mays and Spiess.45, Risk per person per gray versus mean skeletal dose. Their data, plus the incidence rates for these cancers for all Iowa towns with populations 1,000 to 10,000 are shown in Table 4-6. 1972. Diffusion models for the sinuses have not been proposed, but work has been done on the movement of 220Rn through tissue adjacent to bone surfaces. local 36 elevator apprenticeship. For the percent of exposed persons with bone sarcomas, Mays and Lloyd44 give 0.0046% D This is the first report of an explicit test of linearity that has resulted in rejection. This is what your body does with all radioactive elements and he ." Littman, M. S., I. E. Kirsh, and A. T. Keane. i = 0.05 Ci, the total systemic intake in 70 yr for a person drinking 2 liters of water per day at the Environmental Protection Agency's maximum contaminant level of 5 pCi/liter, the ratio is 4,700. For the 27 subjects for whom radium body burden information was available, they estimated that, for airspace thicknesses of 0.5 to 2 cm, the dose from radon and its daughters averaged over a 50-m-thick mucous membrane would be 2 to 5% of the average dose from 226Ra in bone. Occasionally, data from several studies have been analyzed by the same method, and this has helped to illuminate similarities and differences in response among 224Ra, 226Ra, and 228Ra. Dose is used here as a generic term for the variety of dosimetric variables that have been used in the presentation of cancer incidence data. 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. 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. Evans et al. Adults and juveniles were treated separately. This is sometimes in the form of a three-dimensional dose-time-response surface, but more often it is in the form of two-dimensional representations that would result from cutting a three-dimensional surface with planes and plotting the curves where intersections occur. In a review of the papers published in the United States on radium toxicity, and including three cases of radium exposure in Great Britain, Loutit34 made a strong case "that malignant transformation in the lymphomyeloid complex should be added to the accepted malignancies of bone and cranial epithelium as limiting hazards from retention of radium." The case for a dose rate or dose-protraction effect rests on the observation of an association of the linear dose-response slope with dose rate in humans and the unequivocal appearance of a dose-protraction effect in mice and rats. The committee believes a balanced program of radium research should include the following elements. Thus, the model and the Rowland et al. There is no doubt that male and female lung cancers appear to increase with an increase in the radium content of the water, but in the case of female lung cancers the levels were never as great as observed for those who drank surface water. However, no mention of such cases appear in his report. EXtensive Experience with human beings and numerous animal experiments have shown beyond doubt that a portion of any quantity of radium which enters the body will be deposited in the bones, and that osteogenic sarcomas are often associated with small quantities of radium which have been fixed in the bone for considerable periods of time (1). Shifting to a different algorithm for dose calculation would, at a minimum, require demonstration that the new algorithm gives the same numerical values for dose as the Spiess and Mays85 algorithm for subjects of the same age and sex. It should be borne in mind that hot-spot burial only occurs to a significant degree following a single intake or in association with a series of fractions delivered at intervals longer than the time of formation of appositional growth sites, about 100 days in humans. Though one might wish to dispute its existence in humans on statistical grounds in order to defend a claim for greater childhood radiosensitivity, it would seem uneconomical to do so until there is clear evidence of greater radiosensitivity to alpha radiation for the induction of bone cancer in the young of another species. e is the endosteal dose. The subjects used in this analysis were all women employed in the radium-dial-painting industry at an average age of about 19 yr. Individuals may be exposed to higher levels of radium if they live in an area where there are higher levels of radium in rock and soil. 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. 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. s. The analysis of Rowland et al.67 assumes that tumor rate is constant with time for a given intake D 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. Rowland64 published linear and dose-squared exponential relationships that provided good visual fits to the data. Rowland, R. E., A. F. Stehney, and H. F. Lucas. The model was based on a series of three differential equations that described the dynamics of cell survival, replacement, and transformation when bone is irradiated by alpha particles. e A significant role for free radon and the possibly insignificant role for bone volume seekers is not universally acknowledged; the ICRP lumps the sinus and mastoid mucosal tissues together with the endosteal bone tissues and considers that the dose to the first 10 m of tissue from radionuclides deposited in or on bone is the carcinogenically significant dose, thus ignoring trapped radon altogether and taking no account of the epithelial cell locations which are known to be farther from bone than 10 m. Low levels of exposure to radium are normal, and there is no Source: Mays and Spiess. Marshall37 summarized results of limited studies on the rate of diminution of 226Ra specific activity in the hot-spot and diffuse components of beagle vertebral bodies that suggest that the rates of change with time are similar for the maximum hot-spot concentration, the average hot-spot concentration, and the average diffuse concentration. 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. demonstrated an increase of median tumor appearance time with decreasing average skeletal dose rate for a subset of radium-induced bone tumors in humans61 and for bone tumors induced in experimental animals by a variety of radionuclides.60 The validity of the analysis of mouse data has been challenged,62 but not the analysis of human and dog data. The cumulative tumor rate for juveniles and adults at 25 yr after injection, a time after which, it is now thought, no more tumors will occur, were merged into a single data set and fitted with a linear-quadratic exponential relationship: where R is the probability that a tumor will occur per person-gray and D i 2 The ratios of maximum to average lay in the range 837. i, and when based on skeletal dose assumes that tumor rate is constant for a given dose D 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. In the subject without carcinoma, the measured radium concentration in the layer adjacent to the bone surface was only about 3 times the skeletal average. Cumulative incidence, which is the total number of tumors per intake group divided by the numbers of persons alive in that group at the start of observation, was the response parameter. 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. The functional form in the analysis of Rowland et al. 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. i is 226Ra intake, and D In discussing these cases, Wick and Gssner93 noted that three cases of bone cancer were within the range expected for naturally occurring tumors and also within the range expected from a linear extrapolation downward to lower doses from the Spiess et al.88 series. The total numbers of tumors available are too small to assign significance to the small differences in relative frequencies for a given histologic type. The frequency distribution for appearance times shows a heavy concentration of paranasal sinus and mastoid carcinomas with appearance times of greater than 30 yr. For bone tumors there were approximately equal numbers with appearance times of less than or greater than 30 yr.67 Based on the most recent summary of data, 32 bone tumors occurred with appearance times of less than 30 yr among persons with known radiation dose and 29 tumors had occurred with appearance times of 30 yr or greater. i) with 95% confidence that total risk lies between I The thickness of the simple columnar epithelium, including the cilia, is between 30 and 45 m. Washington (DC): National Academies Press (US); 1988. Research should continue on the cells at risk for bone-cancer induction, on cell behavior over time, including where the cells are located in the radiation field at various stages of their life cycles, on tissue modifications which may reduce the radiation dose to the cells, and on the time behavior and distribution of radioactivity in bone. i is IN (t - 10) for t Three-dimensional representation of health effects data, although less common, is more realistic and takes account simultaneously of incidence, exposure, and time. 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) with positive coefficients, not all of which were determined by least-square fitting to the data, based on year of entry and found that: determined the upper and lower boundaries (I The most inclusive and definitive study of leukemia in the U.S. radium-dial workers was published by Spiers et al.83 By including all the dial workers, male and female, who entered the industry before 1970, a total of 2,940 persons who could be located, they were able to document a total of 10 cases of leukemia. 1980. National Research Council (US) Committee on the Biological Effects of Ionizing Radiations. analysis are closely parallel and, as might be expected, lead to the same general conclusion that the response at low doses [where exp(-D) 1] is best described by a function that varies with the square of the absorbed dose. Evans15 listed possible consequences of radium acquisition, which included leukemia and anemia. The radiogenic risk equals the total risk given by one of the preceding expressions minus the natural tumor risk. This trend was subsequently verified by Polednak57 for bone tumors in a larger, all female group of radium-dial workers. It emits alpha, beta, and gamma radiation. Therefore, no judgment can be made as to whether such a layer would develop in response to a single injection of 224Ra or whether the layer could develop fast enough to modify the endosteal cell dosimetry for multiple 224Ra fractions delivered over an extended period of time. l = 10-5 and I Radium has been used commercially in luminous paints for watch and instrument dials and for other luminized objects. For female radium-dial workers first employed before 1930, the only acceptable fit to the data on bone sarcomas per person-year at risk was provided by the functional form (C + D2) exp(-D), which was obtained from the more general expression by setting = 0. Because CLL is not considered to be induced by radiation, the latter case was assumed to be unrelated to the radium exposure. 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. Further efforts to refine dose estimates as a function of time in both man and animals will facilitate the interpretation of animal data in terms of the risks observed in humans. The practical threshold would be the dose at which the minimum appearance time exceeded the maximum human life span, about 50 rad. lefty's wife in donnie brasco; For 222Rn (whose half-life is very long compared with the time required for untrapped atoms within the body to diffuse into the blood supply), this rapid diffusion results in a major reduction of the radiation dose to tissues. 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. 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. provided an interesting and informative commentary on the background and misapplications of the linear nonthreshold hypothesis.17. Could your collectible item contain radium? - Canadian Nuclear Safety 2)exp(-1.1 10-3 Otherwise, the retention in bone is estimated by models. Tumor frequencies for axial and appendicular skeleton are shown in Table 4-1. radiation Flashcards by Ellie Atkinson | Brainscape These cells are within 3080 m of endosteal bone surfaces, defined here as the surfaces bordering the bone-bone marrow interface and the surfaces of the forming and resting haversian canals. In 1977 it was estimated that only 15 people died in the United States from cancers of the auditory tube, middle ear, and mastoid air cells.53 Comparable statistics are lacking for cancers of the ethmoid, frontal, and sphenoid sinuses; but mortality, if scaled from the incidence data, would not be much greater than that caused by cancers of the auditory tube, middle ear, and mastoid air cells. The theory of bone-cancer induction by alpha particles38 offers some insights. According to Hindmarsh et al.26 the most frequent ratio of hotspot to average concentration in bone from a radium-dial painter was 3.5. Otherwise, clearance half-times are about 100 rain and are determined by the blood flow through mucosal tissues.73 The radioactive half-lives of the radon isotopes55 s for 220Rn and 3.8 days for 222Rnare quite different from their clearance half-times. The latter method does not, in effect, correct for selection bias because there is no way to select against such cases. why does radium accumulate in bones? 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. i = 0.5 Ci. Carcinomas of the paranasal sinuses and mastoid air cells may invade the cranial nerves, causing problems with vision or hearing3,23 prior to diagnosis. During life, four quantities that can be monitored include whole-body content of radium, blood concentration, urinary excretion rate, and fecal excretion rate. 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. The dosimetric differences among the three isotopes result from interplay between radioactive decay and the site of radionuclide deposition at the time of decay. 1969. In the analysis by Rowland et al. Because of its preference for bone, radium is commonly referred to as a bone seeker. When plotted, the model shows a nonlinear dose-response relationship for any given time after exposure. s is the sum of the average skeletal doses for 226Ra and 228Ra, in rad. 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. 2 for D Martland,42 summarizing his studies of radium-dial painters, mentioned the development of anemias. Another difference between the analyses done by Rowland et al.