Richard B. Mazess

Performance evaluation of a dual-energy X-ray bone densitometer

SummaryWe tested a dual-energy bone densitometer (LUNAR DPX) that uses a stable x-ray generator and a K-edge filter to achieve the two energy levels. A conventional scintillation detector in pulse-counting mode was used together with a gain stabilizer. The densitometer normally performs spine and femur scans in about 6 minutes and 3 minutes, respectively, with adequate spatial resolution (1.2×1.2mm). Total body scans take either 10 minutes or 20 minutes. The long-term (6 months, n=195) precision of repeat measurement on an 18-cm thick spine phantom was 0.6% at the medium speed. Precision errorin vivo was about 0.6, 0.9 and 1.5% for spine scans (L2-L4) at slow, medium and fast speeds, while the error was 1.2 and 1.5 to 2.0%, respectively, for femur scans at slow and medium speed. The precision of total body bone density was 0.5%in vitro andin vivo. The response to increasing amounts of calcium hydroxyapatite was linear (r=0.99). The densitometer accurately indicated (within 1%) the actual amount of hydroxyapatite after correction for physiological amounts of marrow fat. The measured area corresponded exactly (within 0.5%) to that of known annuli and to the radiographic area of spine phantoms. There was no significant effect of tissue thickness on mass, area, or areal density (BMD) between 10 and 24cm of water. The BMD values for both spine and femurin vivo correlated highly (r=0.98, SEE=.03 g/cm2) with those obtained using conventional153Gd DPA. Similarly, total body BMD correlated highly (r=0.96, SEE=.02g/cm2) with DPA results.

Total body bone mineral and lean body mass by dual-photon absorptiometry. I. Theory and measurement procedure.

SummaryA method was developed for measuring total body bone mineral (TBBM) and lean body mass in vivo using dual-photon absorptiometry. The entire body was scanned in a rectilinear raster (transverse speed of 1 cm/s and longitudinal steps of 2.5 cm) with a modified nuclear medicine scanner and conventional nuclear counting electronics. The source was153Gd (1 Ci) with principal photopeaks at 44 and 100 keV. The scan time was about 70 min with an absorbed dose of under 1 mrem. The low dose allows measurements to be repeated at frequent intervals or used on children. Short-term (months) precision of TBBM was about 1.5% for isolated skeletons and about 2% on normal human subjects. Long-term (years) precision on skeletons was under 3%. The precision of percent fat was 0.9%, which would lead to an error of less than 1% in the TBBM. Geometry of measurements also had minimal (and correctable) influence on the accuracy of results. The accuracy (1 standard error of estimate) of TBBM on isolated skeletons (N=5) was 36 g (equivalent to about 13 g of Ca) with a correlation coefficient of 0.99; this error amounts to about 1–1.5% in normal adults, 2% in older women, and 2.5% in osteoporotic females. The dual-photon absorptiometry method could be implemented in many nuclear medicine departments to follow skeletal changes during growth and aging or to follow the course of a disease or treatment.

Immobilization and bone.

The major advances of the past several years in bone measurement have direct applicat ions for manned space missions, for paraplegics, for patients confined to bed by disease and for the large population of relatively hypodynamic elderly individuals. A meeting held in San Francisco (June 16, 1982) focussed on newer measurement methods and on major results obtained by both histological and noninvasive approaches. The specific aim was to provide the National Aeronautics and Space Administration (NASA) with information to help implement appropriate programs of research. G. Donald Whedon, National Institute of Health, summarized the history of research on bone loss in immobilization and space flight. Negative calcium balance of 150-200 mg/day continued for up to 20 -30 weeks in young bed rest subjects; in the Skylab astronauts, the pattern and degree of calcium loss was similar to that in bed rest but with much inter-individual variation. Calcium losses in patients with spinal cord injuries appeared somewhat higher than in bed rest subjects, and higher losses were found in subjects with complete versus incomplete spinal cord lesions. Calciuria usually declined to the normal range by 30 weeks, but in some patients, a modest elevation was evident even after one year (N. Eric Naftchi, New York University). Losses in paraplegic patients were evidenced h i s t o m o r p h o m e t r i c a l l y by a 33% reduc t i on of trabecular bone volume in iliac crest biopsy over 25 weeks (P. Minaire and C. Alexandre, Hospital Regional, St. Etienne, France). There was both an in-

Increased Growth after Long-Term Oral 1α,25-Vitamin D3 in Childhood Renal Osteodystrophy

We evaluated oral 1,25-vitamin D3 for as long as 26 months in six prepubescent children with renal osteodystrophy previously treated with vitamin D2. Therapy was given at 14 to 41 ng per kilogram per day to correct hypocalcemia and reverse bone disease. Serum levels of 1,25-vitamin D3 were initially reduced at 15 +/- 5 pg per milliliter (mean +/- S.E.M.) and after treatment rose to 54 +/- 13. Serum calcium rose from 7.5 +/- 1.6 mg per deciliter (mean +/- S.D.) to 9.8 +/- 0.6 after one month (P less than 0.02). Alkaline phosphatase activity fell from 536 +/- 298 to 208 +/- 91 IU per liter after 12 months (P less than 0.05). Serum immunoreactive parathyroid levels fell from 900 +/- 562 microliter eq per milliliter 411 +/- 377. Healing of rickets and subperiosteal erosions was found. Remineralization of bone was demonstrated by the photon absorption technic. In four patients growth velocity, evaluated for 12 months before and after therapy, increased from 2.6 +/- 0.8 to 8.0 +/- 3.2 cm per year. Growth velocity per year increased from less than third percentile in each to the 10th to 97th percentile after therapy. Height increment ranged from 27 to 113 per cent of that expected for change in chronologic age and 40 to 114 per cent expected for change in bone age after therapy. This trial demonstrates that oral 1,25-vitamin D3 can reverse renal bone disease and increase growth in uremic children.

Comparison of speed of sound and ultrasound attenuation in the os calcis to bone density of the radius, femur and lumbar spine.

Broadband ultrasonic attenuation (BUA) between 0.1 and 0.6 MHz and speed of sound (SOS) were measured on the os calcis in normal women (n = 40), and women who had mild osteoporosis (n = 36). Comparisons were made between the ultrasonic properties and bone mineral densities (BMD) obtained using photon absorptiometry on the lumbar spine, proximal femur and radius shaft. In the osteoporotic women, whose spine BMD was significantly reduced, BUA and SOS were lower, to about the same degree of significance as radius BMD; ROC analysis demonstrated that for discrimination of spinal osteopenia, the area under the ROC curve was similar for radius BMD, SOS, and BUA. There was a modest correlation (r about 0.65) between either SOS or BUA on the os calcis and BMDs of the spine and radius. Correlations of the SOS and BUA with femoral neck BMD were lower (r about 0.4 to 0.5). The standard error of estimate for both spine and femoral neck BMD was too high (about 0.14 g cm-2) for os calcis measurements to be substituted clinically for densitometry at these fracture sites.

Bone mineral density in women with breast cancer treated with adjuvant tamoxifen for at least two years

SummaryWhile in limited animal studies tamoxifen is reported to protect against loss of bone mineral, data in humans are lacking. We measured bone mineral density (BMD) using single photon absorptiometry at the radius and dual photon absorptiometry at the lumbar spine in breast cancer patients treated with chemotherapy at our institution. In this group, 37 women were not treated with tamoxifen (NT) and 48 women were treated with tamoxifen (T) for at least two years. Younger age, greater weight and height, premenopausal status, and shorter time since menopause were found to be significant predictors of greater BMD. Tamoxifen-treated women had been postmenopausal for more years (p = 0.012). Regression analyses used to adjust for differences in risk of bone loss did not reveal significant differences in BMD between the two groups of women. For the postmenopausal women (27 NT and 34 T subjects), the adjusted mean BMD (g/cm2) at the spine was 1.11 (NT), 1.11 (T) (p = 0.93); and at the radius 0.63 (NT), 0.62 (T) (p = 0.30). This limited retrospective study suggests that tamoxifen does not have ‘anti-estrogenic’ effects on BMD.

Ultrasound transmission measurements through the os calcis

SummaryA method of measuring ultrasonic propagation in the os calcis was devised for assessing bone properties in humans, Speed-of-sound (SOS) and broadband ultrasound attenuation (BUA) were measured using broadband acoustic pulses transmitted and received by a pair of focused transducers. The transducers are mounted coaxially in a water tank with the subjects heel in between. Reproducibility of results in an adult male was 10% for the BUA and 1.2% for the SOS. Both SOS and BUA changed when the transmission path through the os calcis was varied. For a population of normal male subjects, SOS and BUA were correlated with densitometry results on the os calcis, but less well correlated to area density at remote sites.

Enhanced precision with dual-energy x-ray absorptiometry

SummaryRepeat spine and femur measurements (5 per case) were done on 19 subjects with the DPX-L densitometer operating at 3 mA giving a radiation flux fourfold higher than the earlier DPX model. The precision for spine bone mineral density (BMD) was about 0.55% (L2–L4) and 0.48% (L1–L4) for 2-minute scans (2.4 mrem). The precision was only slightly lower (0.4–0.5%) for 4-minute scans (5 mrem) in a subset of 11 subjects. There was a slight precision advantage for the larger L1–L4 area compared with L2–L4 for 2-minute scans, but no advantage for 4-minute scans. The precision for femoral neck BMD was 1.00 and 0.85% for 2- and 4-minute scans, respectively, with proper positioning. The corresponding values for the Wards triangle region of the femur were 2.6 and 1.5%. The precision of spine scans was influenced chiefly by variable region location. The precision of femur scans was affected by both patient positioning and location of the region. The 4-minute scans minimized the number of operator changes necessary for analysis. Precision errors can be reduced by up to 50% with utilization of the higher flux, but this does not obviate the need for care in patient positioning and scan analysis.

Bone mineral status in growth hormone deficiency

Bone mineral status was monitored by photon absorptiometry in 18 children with growth hormone deficiency. Before exogenous growth hormone therapy, bone mineral content, bone width, and BMC/BW were below predicted values. Delayed maturation, as assessed by skeletal age, accounted for approximately 35% of the deficit for these values. Height velocity doubled during therapy, and BMC, BW, and BMC/BW increased commensurate with height and weight increases so that the relative deficit was unchanged. The pathogenesis of relative osteopenia in growth hormone deficiency was not determined.

Total body bone mineral and lean body mass by dual-photon absorptiometry: II. Comparison with total body calcium by neutron activation analysis

SummaryTotal body bone mineral (TBBM) was measured in vivo using dual-photon absorptiometry (DPA) in 10 subjects. The total body calcium (TBCa) was measured in the same subjects using neutron activation analysis. The correlation between the two methods was very high (r>0.99) and the standard error of estimate was low. The TBCa relative to TBBM was about 39%. The two noninvasive methods provided nearly identical indications of skeletal mass, but the radiation exposure with DPA was 500 to 5000 times smaller (0.6 mrem vs 300 to 3000 mrem). The radius shaft bone mineral content was highly correlated with the TBBM (0.97) and the TBCa (0.98) and could be used to estimate the latter variables with errors (1 SEE) of 9% and 6%, respectively.