Faculty Bibliography

Pituitary hormones are essential for bone growth and bone turnover. Hypophysectomy (HX) diminishes mitogenesis and abolishes the high bone turnover rate induced by ovariectomy (OV). It is not known whether the suppressive effect of estrogen on bone resorption is diminished or abolished by HX. The present study investigates the effects of 17 beta-estradiol (E2) (20 micrograms/wk) on cortical and cancellous bone mass and bone turnover as measured by histomorphometry in HX + OV (HO) rats. Sprague-Dawley rats at 2 months of age were OV or HO and the experiment was performed over a 6 week period. Hypophysectomy + OV (HO) resulted in a cessation of periosteal bone formation, and longitudinal bone growth and a decrease in cancellous bone volume. The tibial dry weight and tibial density were significantly lower in the HO than in the intact or OV groups. Administration of E2 to HO rats partially prevented cancellous bone loss, whereas the same dosage of E2 fully prevented cancellous bone loss in rats with OV alone. Nevertheless, cancellous bone volume was higher in the HO + E2 than in the HO-alone groups. Estradiol administration in HO rats did not suppress cancellous bone formation rate or the eroded surface as much as it did in the OV rats. The suppressive effect of E2 on periosteal bone formation rate and mineral apposition rate was also diminished in HO rats. However, factorial ANOVA showed that the effects of E2 on increasing cancellous bone volume and decreasing periosteal bone formation rate and mineral apposition rate were still significant in the HO rats. Tibial dry weight and tibial density did not differ between HO and HO + E2 groups. In conclusion, we have demonstrated that the estrogen-induced effects of preventing cancellous bone loss, of suppressing bone formation, and resorption as seen in OV rats was diminished but not abolished in HO rats.

We examined 23 pairs of black and white premenopausal women to determine whether there were ethnic differences in body composition. The pairs were matched on weight and height. Each woman had measurements of total body water taken by a tritiated water dilution technique, total body nitrogen, and total body carbon by neutron-activation, mineral ash by dual x-ray absorptiometry, and body potassium by whole body counting. Differences between blacks and whites were compared with the use of both the two-compartment and four-compartment models. The two-compartment model showed that in premenopausal black and white women of similar age, heights, and weights, blacks had significantly more lean mass. The four-compartment model resulted in similar conclusions. The black women had larger protein, mineral, and water compartments and less fat than whites. It may be that body weight measurements as an indicator of obesity should be adjusted for black versus white women.

Delayed gamma neutron activation analysis (DGNA) was performed on 99 black and 168 healthy white women, aged 20-80 years, to examine sodium distribution in the two ethnic groups. Elements measured included total body levels of sodium (TBNa) and chlorine (TBCl). The black women were heavier, and consequently had a higher body surface area. Sodium excess (Naes) was calculated from TBNa and TBCl. Total body water was measured by tritiated water dilution. TBNa was higher in black than white women, and this difference persisted when the values were corrected for body surface area. TBNa and Naes declined significantly with age in white women, whereas extracellular fluid sodium (ECFNa) remained constant. The change with age was not statistically significant in black women for TBNa, Naes or ECFNa. Our sample of healthy black women had a higher TBNa and Naes than healthy white women. This difference persisted after adjustment for body surface area, so that values for sodium distribution need to be adjusted for race. The change in TBNa with age in white women appears to be due to their decline of skeletal tissue mass with a consequent decline in nonexchangeable sodium.

Models of involutional bone loss and strategies for the prevention of osteoporosis have been developed for white women. Black women have higher bone densities than white women, but as the black population ages there will be an increasingly higher population of black women with osteoporosis. Strategies should be developed to reduce the risk of black women for fragility fractures. Dual energy X-ray absorptiometry measurements of the total body, femur, spine, and radius were performed on 503 healthy black and white women aged 20-80 years. Indices of bone turnover, the calcitrophic hormones, and radioisotope calcium absorption efficiency were also measured to compare the mechanisms of bone loss.The black women had higher BMD values at every site tested than the white women throughout the adult life cycle. Black women have a higher peak bone mass and a slightly slower rate of adult bone loss from the femur and spine, which are skeletal sites comprised predominantly of trabecular bone. Indices of bone turnover are lower in black women as are serum calcidiol levels and urinary calcium excretion. Serum calcitriol and parathyroid hormone levels are higher in black women and calcium absorption efficiency is the same in black and white women, but dietary calcium intake is lower in black women. Black and white women have a similar pattern of bone loss, with substantial bone loss from the femur and spine prior to menopause and an accelerated bone loss from the total skeleton and radius after menopause. The higher values for bone density in black women as compared with white women are caused by a higher peak bone mass and a slower rate of loss from skeletal sites comprised predominantly of trabecular bone. Low-risk strategies to enhance peak bone mass and to lower bone loss, such as calcium and vitamin D augmentation of the diet, should be examined for black women. The risk vs. benefits of hormonal replacement therapy should be determined, especially in older women.

The four-compartment model of body composition was studied in 112 healthy black women to develop normative data to be used to assess deviations in illness. Each compartment was measured by an independent method: tritiated water dilution, prompt-gamma neutron activation analysis (for nitrogen), inelastic neutron scattering (for carbon) and dual energy x-ray absorptiometry (for calcium). The mean age of the population was 43.2 years. Race was self-declared. The mean values for the four compartments were [kg SE] protein: 9.6 (0.07); mineral 3.0 (0.03); fat 24.2 (0.70); and water 33.1 (0.29). Each of the compartments changed significantly with age (P < .0001). There were declines in total body water, mineral, and protein, whereas fat increased linearly with age. Linear regressions performed on pre- and postmenopausal women showed a significant difference only for the mineral compartment. Various models were fit to the data to adjust for body size and age. The equation y = age + height + weight fits the data as well as the other models. Equations and graphs were developed to assess each compartment using this linear model and may be used to assess the body composition status of healthy and ill black women. Although black women tended to be heavier than white women, after controlling for differences in body weight (and age) black women had a greater mass of protein, mineral, and water and a similar fat store. These differences, while statistically significant, were not of great magnitude. This was a cross-sectional study and suspected trends with aging must be confirmed by a longitudinal study.

The aim of this study is to examine the interrelationship of pituitary and ovarian hormone deficiency on the regulation of bone growth and bone formation rate. 48 female rats, at 3 months of age, were divided into age-matched intact control, hypophysectomized (HX), ovariectomized (OV), and HX + OV groups. Ten rats were killed at 3 months of age as baseline controls, and the rest of the animals were killed 5 weeks after surgery. Serum levels of osteocalcin and dynamic histomorphometry on the periosteal surface of the tibial shaft and fifth lumbar vertebrae were measured to evaluate systemic and local bone turnover. Tibial and fourth lumbar vertebral bone area, bone mineral content, and bone density were measured by dual-energy X-ray absorptiometry (DXA). Our results confirmed that OV increased and HX suppressed systemic and periosteal bone formation parameters in both bone sites, OV increased and HX suppressed the gain in bone size and bone mass. When OV rats were HX, the serum levels of osteocalcin and periosteal bone formation parameters of the tibial shaft and the fifth lumbar vertebrae were, however, depressed and did not differ from that of the HX alone. DXA results show that the effect of OV on bone size and bone mass is also abolished by HX. In conclusion, we have demonstrated that OV increases tibial and lumbar vertebral bone formation and bone growth and this effect is pituitary hormone dependent.