Faculty Bibliography

The delayed-gamma neutron activation facility at Brookhaven National Laboratory was originally calibrated using an anthropomorphic hollow phantom filled with solutions containing predetermined amounts of Ca. However, 99% of the total Ca in the human body is not homogeneously distributed but contained within the skeleton. Recently, an artificial skeleton was designed, constructed, and placed in a bottle phantom to better represent the Ca distribution in the human body. Neutron activation measurements of an anthropomorphic and a bottle (with no skeleton) phantom demonstrate that the difference in size and shape between the two phantoms changes the total body calcium results by less than 1%. To test the artificial skeleton, two small polyethylene jerry-can phantoms were made, one with a femur from a cadaver and one with an artificial bone in exactly the same geometry. The femur was ashed following the neutron activation measurements for chemical analysis of Ca. Results indicate that the artificial bone closely simulates the real bone in neutron activation analysis and provides accurate calibration for Ca measurements. Therefore, the calibration of the delayed-gamma neutron activation system is now based on the new bottle phantom containing an artificial skeleton. This change has improved the accuracy of measurement for total body calcium. Also, the simple geometry of this phantom and the artificial skeleton allows us to simulate the neutron activation process using a Monte Carlo code, which enables us to calibrate the system for human subjects larger and smaller than the phantoms used as standards.

The four-compartment model of body composition was examined in 155 white women through measurement of total body carbon (TBC), nitrogen (TBN), calcium (TBCa), and water levels. The age (mean +/- SD) of the population was 51.4 +/- 13.5 years, and values for the four compartments were as follows (in kilograms): protein 8.9 +/- 1.0, water 30.9 +/- 3.5, mineral 2.6 +/- 0.4, and fat 22.6 +/- 7.3. There was a linear change with age for protein and water, whereas mineral and fat were curvilinear. These latter two compartments also showed differences in premenopausal and postmenopausal rates of change. Various models were fit to the data to adjust for body size and age. Each of the four compartments (mineral, water, fat, and protein) changed with age, with fat increasing and the other compartments declining. The equation, y = age + age2 + height + weight, fit the data as well as the other models. Equations are provided to assess body composition in populations with disorders of nutrition, as well as other illnesses, using height, weight, and age as covariates. Since this was a cross-sectional study, longitudinal studies will have to be performed to confirm the accuracy of rates of change with age predicted with each compartment.

White women have a higher rate of age-specific hip fractures than black women. Recently, femoral dimensions have been implicated in osteoporotic fractures. To study racial differences in femoral dimensions, dual X-ray absorptiometry scans were obtained for two similar groups of 50 white women and 50 black women. We measured the hip axis length (the distance from below the lateral aspect of the greater trochanter to the inner pelvic brim), the neck width and the neck/shaft angle on the scan print-out. The observer was masked to the race of the subject. The results were analyzed using the independent t-test and showed that the hip axis length and the neck width were significantly longer in the white women than in the black women (p values < 0.05 and < 0.02 respectively) but that the neck/shaft angle was not statistically different in the two groups. We conclude that femoral geometry differs among races. Whether this contributes to the lower risk of hip fracture in black women will require prospectively based studies.

The mechanism of action of retardation of postmenopausal bone loss may be different for dietary calcium augmentation and hormonal replacement therapy (HRT). We performed a three-arm, placebo-controlled, randomized clinical trial comparing an intake of calcium of 1700 mg with: (1) calcium augmentation with HRT and (2) placebo. One hundred and eighteen women entered the study; 17 patients dropped out of the study. The vast majority of women were less than 2 years postmenopause. Bone mineral density declined significantly in the placebo group. The previously reported rates of change in the HRT group were significantly positive for total body calcium and the trochanter and not significantly different from zero for the others. The rate of change in the calcium augmentation group was intermediate between that in the two other groups, and achieved statistical significance compared with placebo for the total body calcium measurement and for the neck of the femur. Measurements were made prior to treatment and at the end of the study (2.9 years +/- 1.1 SD) for parameters of bone turnover and the calcitrophic hormones, to examine whether the mechanism of action was different for calcium augmentation versus hormonal therapy. There were no changes in the placebo group. The calcium augmentation group had a significant increase in 24-h urinary calcium and declining values for urinary collagen cross-links (pyridinium and deoxypyridinium), urinary hydroxyproline and calcitriol. The group treated with HRT and dietary calcium augmentation also had an increase in urinary calcium and a decline in collagen cross-links and urinary hydroxyproline and skeletal alkaline phosphatase; serum calcitriol did not change. The HRT group also displayed a drop in serum osteocalcin, and an increase in nephrogenous cAMP. Serum parathyroid hormone remained unchanged in all groups. Dietary calcium augmentation retards postmenopausal bone loss by decreasing resorption. The addition of HRT results in a more marked decline in bone resorption parameters and a suppression of parameters of bone formation. Whereas calcium augmentation suppressed calcitriol levels, the addition of HRT resulted in maintenance of calcitriol levels, possibly through enhancement of the renal effects of parathyroid hormone, although other mechanisms are possible.

Predicting the risk of fracture in osteopenic patients depends chiefly on BMD, age, and the history of previous fractures. Age may be a surrogate for bone quality and extraskeletal factors such as the propensity to fall and cushioning by soft tissue. Various investigators have itemized other risk factors for fracture. We include a table showing fracture risk by age group for patients in the next 10 years based on the three major risk factors.

This experiment studied the effects of hypophysectomy (HX) and ovariectomy (OV) on cancellous bone in the proximal tibia and distal 5th lumbar vertebra by dynamic histomorphometry. Forty-eight female Sprague-Dawley rats, 3 months of age, were divided into age-matched control, HX, OV, and HX + OV (HO) groups. Ten rats were sacrificed at 3 months of age as baseline controls, and the rest of the animals were sacrificed 5 weeks after the surgery. While the age-matched controls, and the OV rats significantly increased in body weight compared with the baseline control rats, cancellous bone volumes in the proximal tibia and distal 5th lumbar vertebra increased in the age-matched controls and decreased in the OV rats. In the HX and HO rats, body weight equaled baseline control values, and their cancellous bone volumes were decreased with a poorer trabecular architecture in both bone sites. In all HX, OV, and HO rats, uterine weight and serum estradiol were significantly decreased. OV significantly increased longitudinal bone growth and the tissue- and surface-based bone formation and bone resorption parameters in both the proximal tibia and 5th lumbar vertebra (p < 0.05). HX alone or HO significantly decreased longitudinal bone growth and the tissue-based bone formation rate without significantly affecting surface-based bone formation and bone resorption parameters when compared with the age-matched controls. No significant differences were detected in any variables between the HX alone and HO rats.(ABSTRACT TRUNCATED AT 250 WORDS)