Bone Lead Test - K XRF
Why measure lead in bone?
The health effects of lead
The harmful health effects of lead have been known for thousands of years, but observations of injurious effects at low levels of lead have been the subject of increasing concern in the past few years. Research has pointed to possible dangers faced by specific populations who risk lead exposure from mobilization of their body lead stores, e.g., children, pregnant women and osteoporotics. Lead toxicity is reported to be a major public health problem in the United States today. The general population is exposed to lead in their environment. This lead can come from several sources, such as house paint, water and soil. Although lead has been banned from house paint, older housing stock still contains lead paint, which can contaminate household dust. Lead was removed from American gasoline in the early 1980s, and lead levels in children have fallen considerably, yet this previous use has resulted in soil contamination that still exists. Lead continues in use in many plumbing fittings, and many areas still receive their water supply through lead pipes. All of these factors can result in elevated lead absorption.
Environmental exposure to lead is not the only source of lead-related health effects. Many industrial workers in the United States have potential occupational exposure to lead, and lead poisoning is still seen at occupational health clinics.
Clinical lead poisoning in itself does not define the extent of lead-related health problems. Research has shown that lead exposure, even at legally permissible levels, can result in harmful, though subclinical, effects. Some of the earliest symptoms of the ailment are non-specific, such as fatigue and muscle pain, and are frequently ascribed to factors other than lead poisoning. Other effects include changes in kidney function, inhibited central nervous system function and reduced nerve conduction velocity, the latter having been demonstrated in lead workers who showed no symptoms. This means that more adults may be affected by both environmental and occupational lead exposure than can be estimated from the numbers who present at clinics.
For more information on lead and your health, go to the Mount Sinai Selikoff Centers for Occupational Health website at www.mountsinai.org/selikoff.
Lead in blood
At the present time, exposure to lead is most commonly monitored by measuring blood-lead levels. The criteria for lead poisoning and lead toxicity are based on blood lead as a standard. However, the biological half-life of lead in blood is approximately 36 days, making blood lead an indicator only of recent lead exposure. Blood lead reflects chronic exposure only when exposure is constant, and deleterious health effects of lead resulting from long-term lead exposure will be correlated with current blood-lead levels only if lead exposure has been relatively constant over a long period of time, up to the time of sampling.
Physiologically, the measurement of lead in blood is not a direct assessment of target organ dose, since the red cell is not a critical target for lead toxicity. Kinetically, blood is not a good analog for critical targets, such as soft tissue, because of the relatively short half-life of lead in blood compared to that of the target organs or bone.
Blood lead is not known for the general population
Long-term lead exposure is a primary health concern but can rarely be ascertained from blood-lead records. No one in the general population has an adequate blood-lead measurement history. However, 109Cd-based lead K-shell X-Ray Fluorescence (K XRF) bone-lead measurements allow the direct measurement of long-term lead exposure.
At the present time, little is known about the range of chronic environmental exposures in the general population. Further research is required for the full implications of chronic lead exposure to be thoroughly understood. However, 109Cd K XRF bone-lead measurements have the potential to enhance our understanding of the effects of low-level lead exposure and consequently to determine whether the current intervention criteria, which are based on blood-lead levels, afford adequate protection against the effects of lead. Bone-lead measurements may also provide an additional screening technique in the identification of high-risk populations.
Lead in bone
Lead is predominantly stored in the human body in calcified tissues; 90-95% of the total lead burden is contained within bone in non-occupationally exposed adults. The total lead content of bone has been reported to be up to 200 mg in 60-70 year-old men, less in women. The turnover rate of lead in cortical and trabecular bone is slow; quantitative estimates of the half-life vary, but there is a consensus that it is of the order of years or even decades. Therefore, through childhood and most of adult life, lead exposure from both environmental and occupational sources results in an increased lead concentration within the bone matrix. A measure of bone-lead content thus reflects integrated or cumulative, and thus long-term or chronic, lead exposure and provides a useful surrogate indicator of the cumulative dose of lead presented over time to the target organs of lead.
In vivo bone-lead measurements may therefore clarify the risks associated with lead exposure in two ways: (1) health effects associated with chronic lead exposure may be identified by their correlation with bone-lead level; and (2) bone-lead measurements may ultimately allow the identification of subjects at risk from mobilization of their body lead stores and allow appropriate intervention strategies to be devised.
Possible mobilization of lead from bone
Under conditions where bone physiology is undergoing a period of change, such as during pregnancy, aging and osteoporosis, it would appear that lead can be released from the bone mineral matrix, increasing blood-lead levels and constituting a further source of lead exposure. It would seem likely that the level of this endogenous exposure would be dependent on bone-lead burden.
K X-Ray Fluorescence measures long-term lead exposure
Several large in vivo studies have confirmed that 109Cd lead K-shell XRF bone-lead measurement is a measure of long-term lead exposure. Bone-lead measurements have been performed on thousands of occupationally exposed workers in numerous countries. Initially, occupationally exposed groups were studied because extensive blood-lead records were available for these groups; in some cases, records extended as far back as 1950. It was found in all the individual studies that bone-lead concentration of tibia, calcaneus and sternum correlated with the “Cumulative Blood Lead Index” (CBLI). The CBLI is an integrated, time-weighted average blood-lead level and thus corresponds to total lead exposure. The studies reported that 109Cd K XRF bone-lead measurements could therefore be considered a measure of cumulative lead exposure.
Evidence therefore exists that the 109Cd K XRF method can provide an accurate measurement of bone-lead concentration to well within the currently available levels of precision, and further that this measurement of lead in bone can be considered a measure of long-term lead exposure.
The radiation dose and consequent risk arising from a K XRF bone-lead measurement are very small for all age groups, including children.
Measuring Lead in Bone: A Practical Description
To undergo a bone-lead measurement, one sits in a lead-free, plastic chair for 30–40 minutes that includes preparation and the bone-lead measurement itself. The variation in time results from the decay of the 109Cd source over time: as the source grows older and, consequently, weaker, the measurement time is increased until, at its least active, the measurement is conducted for 40 minutes. The increase in time ensures constant measurement precision and does not, of course, mean a larger dose. Preparation is simply rolling up of the trouser/pant leg and wiping with diluted glacial acetic acid (3%) to remove any lead contamination from the skin.
One’s leg is then gently restrained to maintain 3 cm between the skin and the source. Restraint is performed with broad nylon straps fitted with non-metallic fasteners and is not uncomfortable. When one is positioned, the source/detector is moved into place. The source/detector combination is mounted on a platform that moves in all three spatial dimensions (XYZ). Measurements are made at the mid-shaft of the tibia (shin), or the middle of the calcaneus (heel) and the patella (knee cap). When positioning the system, one is shielded from the source photons by a source-shield of tungsten alloy that is retracted when the measurement begins.
Pediatric subjects are “immobilized” in the same ways as adults: only the leg needs to be restrained. Sedation of pediatric subjects is not necessary because the XRF measurement result is independent of non-gross subject movement. Pediatric subjects are not held by another person, and there is no need to exclude the custodian of the child from the measurement room.
Cleaning the leg
The XRF system in place
A measurement in progress in Taiwan
Measuring Lead in Bone: A Technical Description
The presence of most toxic heavy metals in the body can be measured in the laboratory via the analysis of blood, urine or biopsy samples. However, the sensitivity of such measurements varies from element to element and, more importantly, the measurements do not always directly indicate the amount of the element in the organ of accumulation or interaction. For example, lead in blood does not measure cumulative exposure, because it has a biological half-life of approximately 36 days. In vivo elemental analysis provides a direct, non-invasive measurement of the element of interest (lead) in the organ of accumulation (bone). The principle of X-Ray Fluorescence (XRF) is the use of photons to fluoresce atoms of the element of interest and measurement of the subsequently produced X-rays that are characteristic of the element of interest; the more element present in the sample, the more X-rays are produced.
Photons from the ‘fluorescing source’ can remove an inner shell electron from a lead atom, leaving the lead atom in an excited state. De-excitation can occur via the emission of one of a series of X-rays, the energies of which are specific to lead. The X-rays are recorded by a radiation detector and the number of X-rays is directly proportional to the amount of lead present in the bone. Appropriate calibration of the system against lead-doped samples allows the number of emitted lead X-rays to be quantified as a measure of lead in the sample. Bone-lead measurements are non-invasive; the subject is required to sit in a chair and have the measurement system moved into place. 109Cd-based lead K-shell XRF measurements are typically performed for approximately 30 minutes.
Lead K-shell X-rays are fluoresced with cyclotron-produced 109Cd in a solid, encapsulated form. The source is usually 1.295 GBq (35 m Ci) activity at delivery. The 109Cd source is a sealed source.
At all times the source has 0.25 mm of copper over the source window that absorbs 98.25% of the silver X-rays that accompany the decay of 109Cd. When the source is being used for measurements, the source in its holder / collimator is removed from the lead storage container and mounted onto the middle of the end-cap of a 50 mm diameter intrinsic germanium detector; the 109Cd source can thereby be mounted co-axially with and on the front of the detector.
Fluorescent X-ray emissions are detected and quantified with the detector, which has a built-in, resistive feedback preamplifier connected to a standard spectroscopy system of electronics, i.e., amplifier, digitizer and multi-channel, pulse-height analyzer.
In addition to in vivo spectra, calibration spectra are obtained from lead-doped, plaster-of-Paris phantoms containing between 0 and 150 mg lead per gram of plaster.
Source holder with copper filter mounted onto a detector end-cap and measuring lead in the leg on the right of the photograph. This photograph also shows a section of the leg brace (far left), which is attached around the aluminum detector housing.
The 109Cd is placed in a cylindrical source holder / collimator (6 mm diameter, 6 mm length) of 90% tungsten, 6% nickel and 4% copper. The source fits snugly within, but is removable from, the source holder. The source is not removed from the source holder / collimator except for the mandated biannual wipe tests.
Advantages of the technique we use for bone lead XRF
The 109Cd source is mounted co-axially on the front of an intrinsic germanium detector. The detector thus measures the radiation spectrum backscattered into it and is referred to as being in a “backscatter geometry”. The energy of the incident photons is 88.035 keV, and such scattering ensures that the Compton peak lies at 65 keV, below the energy of the lead K X-ray peaks (74-87 keV). This lowers the background under the lead peaks and improves the detection limit. A significant feature of the spectrum is the elastic scatter peak from the 109Cd gamma rays, which interact with calcium and phosphorous in bone such that their energy is essentially unchanged; the peak thus occurs at 88 keV. The probability of a photon being elastically scattered by an element of atomic number Z depends on Z5 or Z6, and in a bone-lead measurement 98-99% of elastically scattered photons arise from the bone mineral. Normalizing the lead X-ray peak counts to the elastic scatter peak counts results in a bone-lead content in units of mg lead per gram of bone mineral. The advantage of the normalization is that a measurement result is thus independent of bone shape, size or mass of tissue overlay thickness, source-to-subject distance, orientation of detector assembly with respect to the bone, the orientation of the bone within the leg and of (minor) subject movement. No correction factors need therefore be applied to take these factors into account, and subjects need not be restrained or sedated in any way. The measurement precision (the uncertainty in an individual measurement result) does vary somewhat, depending upon the source-to-bone distance and the thickness of overlying tissue.
The considerable robustness of the K XRF technique and the consequent ease with which different bone sites can be measured are probably the reasons for the widespread acceptance of this technique among the research community.