The value and limitation of dual-energy X-ray absorptiometry.

In population studies, in which patients and controls are of comparable size, bone mineral area density (BMD) gives reliable results for mean bone mass data although, with sequential data, BMD may under-estimate the degree of change in bone mass. In children BMD data should be reliable, provided that patients and controls, matched for age and sex, are also of the same size. With disease children may be small for their age so that low bone mass by BMD may be due to small body size and not necessarily to osteopoenia. In these situations the bone mineral content (BMC) index may be more reliable than BMD. To assess bone mass status in individuals, BMC index, as well as BMD, should be used, particularly with adults at the extremes of body size (the very small or very tall).

Nutritional assessment.

Measurements of body composition are made to assess nutritional status. The measurements used for these studies should be selected on the basis of reliability, as well as simplicity and costs, and reliability depends on the information required. In normal adults simple estimates of fat and lean tissue (LBM), i.e. the anthropometric measurements of weight, height and skin fold thickness, should be sufficient since the proportions, in LBM, of water, protein and bone mineral are relatively constant. Measurements of body water (by isotope dilution or bioelectrical impedance) allow indirect estimates of fat and LBM that are reliable, provided that water is a constant proportion of LBM. In disease states, however, including renal disease, it is well established that the proportion of water in LBM varies from significant water overload to dehydration. In disease, it is important to determine not only total LBM but also the quality of LBM, determining essential body protein as well as body water. Body protein can be measured directly by nuclear techniques. This procedure should be more readily available for the clinical investigation of nutritional status.

Uptake of fluorine in cortical and trabecular bone.

Nuclear magnetic resonance techniques can measure the fluoride levels in bone of the finger after a patient has ingested F in the treatment of osteoporosis, but does uptake in cortical bone reflect uptake in the critical trabecular bone? Investigation has been made of the relative uptake of fluoride from drinking water into trabecular and cortical bone of the rat. For fine detail of the uptake of F into the femur and vertebra, microprobe techniques were used with a spatial resolution of 10 microns; for broader studies, treating the femur as representative of cortical bone and the vertebra as typical of trabecular bone, chemical techniques using spectroscopy and ion-selective electrodes were employed. The conclusion is that in the rat uptake of F by cortical bone is indicative of uptake by trabecular bone, and that therefore as a working hypothesis NMR measurement of F in the finger may be taken as reflecting uptake of F by trabecular bone.

Recent developments in in vivo neutron activation analysis facilities.

Two new facilities for in vivo activation analysis of patients have been designed, developed, and constructed at Toronto General Hospital. One of these is for the determination of body calcium for the diagnosis of osteoporosis and other diseases associated with bone loss. The other is for the measurement of total body nitrogen for the determination of protein status. These facilities replace old university facilities and take into account the comfort and management of patients. In addition, in the case of the calcium facility, the precision of the measurements has been improved because of larger detector volume and increased neutron source strength. Both the facilities are now in routine hospital clinical use.

Improved clinical facility for in vivo nitrogen measurement.

The design and construction of a hospital clinical facility for in vivo prompt gamma neutron activation analysis for total body nitrogen (TBN) measurement is described. The use of 252Cf neutron sources gives a better signal-to-background ratio compared with 238Pu-Be sources of equal strength, thus yielding better reproducibility of measurements. By measuring the hydrogen and nitrogen signals separately using appropriate gating circuits, signal-to-background ratio is further improved. Measurements using a urea phantom (5.63 kg nitrogen as urea in 34.53 kg of water) show that 2 x 6 micrograms 252Cf sources gives a nitrogen signal-to-background ratio of 5.6 (compared with 3.4 in the case of a 2 x 10 Ci 238Pu-Be source) and a reproducibility for nitrogen signal of +/- 1.1% (CV) and for hydrogen signal (internal standard) of +/- 2.33% (CV). Approximately 30 minutes of patient's time is required for each TBN measurement with an estimated reproducibility of +/- 3.8% (CV). The radiation dose to the patient is about 0.2 mSv (effective dose equivalent; QF = 10) per 20 min measurement. A report for the clinician is produced within a few minutes after the measurement by a dedicated IBM-PC computer. The entire facility is clean, comfortable and the electronics and computer processing are simple and economical.

In vivo 19F spin relaxation in index finger bones.

19F free induction decay (FID) signals have been observed from the index fingers of four male and two female adult volunteers using a 27-MHz pulsed nuclear magnetic resonance spectrometer equipped with a split ring resonator probe. The value of the in vivo spin-lattice relaxation time T1 of the fluoride ions naturally accumulated in bone mineral has been determined to be 2.0 +/- 0.3 s. The shape of the observed FID signals in the inhomogeneous external magnetic field indicates that the F distribution is not uniform along the length of the finger. The fluoride ion content of the index finger (within a 65-mm length from its distal end) was measured with a sensitivity of +/- 0.5 mg F within a 30-min observation time.

In vivo measurement of accumulated bone fluorides by nuclear magnetic resonance.

We have developed a localized noninvasive nuclear magnetic resonance (NMR) method for determining the accumulated bone fluoride content in human index fingers. Using a 27 MHz "split-ring" resonator probe, we measure the total fluoride (F) content within a 6.5 cm length of the distal end of the index finger from a calibrated determination of the intensity of the observed 19F free induction decay (FID) signal. Since fluoride impurities accumulate almost exclusively in bone mineral, the 19F resonance signal is broadened by rigid lattice magnetic dipole-dipole interactions, causing the FID signal to have a relatively short lifetime of approximately 75 microseconds. This short signal lifetime, plus the weakness of the signal strength prevents conventional magnetic resonance imaging equipment from observing the 19F in bone mineral. Nevertheless, we have achieved an in vivo sensitivity of +/- 0.5 mg fluoride in an observation period of 30 min. Assuming an index finger has between 0.25 and 0.5 g of bone calcium, this sensitivity is just sufficient to detect fluorides in the index finger of most adults whose bone fluoride concentration is greater than 2.0 mg fluoride/g calcium (0.8 mg/g ash weight). We are particularly interested in using this new NMR technique to monitor the rate of bone fluoride accumulation in osteoporotic patients receiving therapeutic levels of fluoride in their diets.

Investigation of factors which lead to the background in the measurement of nitrogen by IVNAA.

A major problem in the measurement of nitrogen in the body by in vivo neutron activation analysis is the size of the background. Investigations show that random summing of gamma rays in the range 4-7 MeV is a major contributor. By direct comparison, 252Cf is shown to be a better neutron source than Pu-Be in this regard. Data are presented on the contribution to the background of water and chloride in the body.

In vivo analysis of bone fluoride content via NMR.

In vivo free induction decay signals have been detected from the fluoride ion (F) content of human finger bones by a 27 MHz pulsed single-coil nuclear magnetic resonance (NMR) spectrometer. The intensity of these dipolar-broadened NMR signals can be used to estimate the F content of the middle phalanx of the index finger. This NMR procedure is the first non-invasive method capable of monitoring bone F contents. The preliminary results we report were obtained from patients known by previous biopsies to have relatively high bone F concentrations in their pelvis. This new monitoring technique does not yet have adequate sensitivity or accuracy for routine clinical use. As a research technique, it has applications to the diagnosis of fluorosis (both industrial and endemic) as well as renal osteodystrophy, and to the establishment of optimal NaF does for the treatment of osteoporosis.

A system for in vivo measurement of bone calcium by local neutron activation of the hand.

A 252Cf neutron-irradiation facility designed specifically for clinical in vivo measurement of calcium in the hand is described. Results of preliminary measurements are presented. Hand phantoms were exposed to the neutron beam for 10 min and the induced 49Ca activities were counted for 10 min after an elapsed time of 2 min. The results indicate that with a 2 X 100 micrograms 252Cf neutron source and two 20.3 X 12.7 cm NaI crystals, the counts per gram of bone mineral mass changes by about 4% for each 100 cm3 change in the overall volume (soft tissue plus bone) of the hand. For hands of equal volumes the counts per gram are expected to be almost independent of the bone volume. With an absorbed dose equivalent of 150 mSv (15 rem), the sensitivity is about 200 counts per 10 min per gram Ca. The statistical reproducibility of the results is better than 3% for the average value of 11 g Ca in the normal hand.

Estimates of lifetime lung cancer risks resulting from Rn progeny exposure.

Data on five mining populations exposed to Rn progeny have been used to estimate the lifetime risk of lung cancer resulting from occupational and environmental exposure under current standards. Slopes of dose-response relations for lung cancer show a tendency to decrease with increasing dose. Our best estimate of curvilinearity is given by raising dose to the power 0.92 +/- 0.07, but the improvement in fit beyond simple linearity is not significant. On the other hand, the addition of a cell-killing term significantly improves the fit of the linear model. In any event, linear extrapolation is unlikely to underestimate the excess risk at low doses by more than a factor of 1.5. However, these inferences about curvilinearity are highly subject to error from the choice of reference populations, dosimetry, and latency. Under the linear-cell-killing model, our best estimate of excess relative risk is 2.28 +/- 0.35 per 100 working level month (WLM) (a doubling dose of 44 WLM). Attributable risks in these five studies range from 3.4-17.8 per 10(6) person-yr WLM-1. Risks from Rn progeny appear to interact with age and smoking in a form intermediate between additive and multiplicative. The "relative risk" model is therefore preferable for projecting lifetime risks, but life-table projections are described for a wide variety of assumptions. Our best estimate of the effect of a 50-yr occupational exposure to 4 WLM yr-1 is 130 excess lung cancer deaths per 1000 persons (0.65 per 1000 person-WLM), with a range from 60-250 per 1000. Similar calculations for lifetime exposure to an additional 0.02 working level (WL) beyond normal background produces an estimate of 20 excess lung cancers per 1000 persons.