A B S T R A C T We measured bone mineral density (BMD) of the proximal femur, lumbar spine, or both by dual photon absorptiometry in 205 normal volunteers (123 women and 82 men; age range 20 to 92 yr) and in 31 patients with hip fractures (26 women and 5 men; mean age, 78 yr). For normal women, the regression of BMD on age was negative and linear at each site; overall decrease during life was 58% in the femoral neck, 53% in the intertrochanteric region of the femur, and 42% in the lumbar spine. For normal men, the age regression was linear also; the rate of decrease in BMD was two-thirds of that in women for femoral neck and intertrochanteric femur but was only one-fourth of that in women for lumbar spine. This difference may explain why the female/male ratio is 2:1 for hip fractures but 8:1 for vertebral fractures.The standard deviation (Z-score) from the sex-specific age-adjusted normal mean in 26 women with hip fracture averaged -0.31 (P < 0.05) for the femoral neck, -0.53 (P < 0.01) for the intertrochanteric femur, and +0.24 (NS) for the lumbar spine; results were similar for 5 men with hip fractures. By contrast, for 27 additional women, ages 51-65 yr, with only nontraumatic vertebral fractures, the Z-score was -1.92 (P < 0.001) for the lumbar spine. Thus, contrary to the view that osteoporosis is a single age-related entity, our data suggest the existence of two distinct syndromes. One form, "postmenopausal osteoporosis," is
Dual-photon absorptiometry with gadolinium 153 was used to measure the mineral content of lumbar vertebrae in cadavers, excised vertebrae with marrow, and dry, marrow-free vertebrae. The error introduced by the surrounding soft tissue of cadavers was 3%, and the error in determining mineral mass or density in excised vertebrae was about 5%. The correlation coefficient between the results of Gd-153 and corrected iodine 125 (single-photon) absorptiometry on 24 femoral necks was 0.99, and the predictive error was 3.7%. Dual-photon absorptiometry accurately indicates bone mass and bone density and is only slightly affected by either surrounding tissue or fat changes in bone marrow.
A closed tibial fracture, which was controlled by an intramedullary stainless steel pin, was created in 16 rabbits. Eight rabbits were treated with 75 ng of 1,25(OH)2D3 daily as subcutaneous (s.c.) injections. After three weeks, the fractured tibia resisted a force of 101.7 +/- 21.0 Newtons in the control group and 57.3 +/- 8.0 Newtons in animals given 1,25(OH)2D3 (m +/- SE, P less than 0.05). In another group of eight rabbits, the left hindleg was immobilized in a plastic splint. Four rabbits were given 75 ng of 1,25(OH)2D3/day s.c. and the effect of immobilization was studied on the calcaneus. Bone ash/cm3 of the calcaneus on the immobilized side was decreased by 11 +/- 2% in control rabbits and by 20 +/- 2% in the group treated with 1,25(OH)2D3 indicating a more advanced immobilization osteoporosis (m +/- SE, P less than 0.05), which was also demonstrated by studies of bone density. Eighteen rabbits were used in a study of the effects of 1,25(OH)2D3 on the development of prednisolone osteoporosis. The dose of prednisolone was 2.5 mg per day, given by the oral route. After four months, the density of the femur was 1.53 +/- 0.02 g/cm2 in control rabbits and 1.42 +/- 0.01 in prednisolone-treated animals (P less than 0.01). In rabbits additionally given 1,25(OH)2D3, the mean value for bone density was further lowered (n.s.). It appears that 1,25(OH)2D3 exaggerates disuse osteoporosis and prednisolone osteoporosis and impairs fracture healing in rabbits. These results differ from what has been shown earlier with 1,25(OH)2D3 treatment in the rat.
Milliken et al 1 recently tested the ability of a bone densitometer (Lunar DPX) that uses dual-energy x-ray absorptiometry (DEXA) to measure arti®cial compositional changes induced by placing packets (1.4±2.8 kg) of lard, water, or ground beef on human subjects. There was no change of BMC induced by these alterations of composition. DPX scans determined actual changes of soft-tissue mass quite well, but there were errors in estimation of packet composition. Readers should recognize, however, that the regional changes of percent fat amounted to only $1%. The uncertainty of percent fat measurement with the DPX is approximately 1%; it is dif®cult to ascertain changes accurately that are comparable to the precision error of the method. This is particularly true for packets placed on the trunk, because the packets will be occluded not only by the spine, but by the pelvis, ribs, and sternum; only the unoccluded portion can be measured. Other groups 2,3 have used similar tests to examine the ability of DEXA to determine compositional alterations. All these tests produce nonphysiological alterations of composition which differ from those designed to be detected by the software. Additional re®nement is needed in developing more`physiological' tests, since bad testing usually gives bad results. The DPX has been shown to measure the fat content of meat blocks with 1% accuracy over a range of 5±50%, and has also been shown to measure chemical composition ex vivo with a similar exactitude. 4 A recent study by Mitchell et al, 5 using chemical analysis of 137 pigs, showed 1% error predicting percent fat from DEXA in animals from 30±90 kg. Changes of mass are measured accurately in vivo, and composition changes accord with those expected. About 60±90% of weight loss is detected as fat loss, while 90% of weight change ($2 kg) with dialysis is detected as a change in lean tissue. 6±11 The net conclusion of the studies to date is that DEXA accurately measures composition in vitro and in vivo. One can only conclude that the arti®cial alterations of composition used by some physiologists to test DEXA software are inappropriate to simulate physiological changes of composition.
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