ALBERT

Notes: Abstract The purpose of this study was to examine the effects of estrogen replacement, in concert with three different progestin regimens, on the mechanical properties of rat lumbar vertebrae. Ninety-two Sprague-Dawley rats (11 months old) were divided into six groups for treatment. The first group was an intact control, the second group (OVX) was ovariectomized only, and the third group (estrogen-only) was ovariectomized and received continuous estrogen through a 17β-estradiol implant. The remaining groups were ovariectomized and received estrogen and progestin (norethindrone, NET) therapy; 3 μg of NET was injected daily (estrogen plus continuous NET), or 6 μg of NET was injected for 14 consecutive days of a 28-day cycle (estrogen plus cyclic NET), or for 3 consecutive days of a 6-day cycle estrogen plus interrupted NET). The animals were sacrificed after 6 months, and the vertebrae were dissected out. The vertebral processes of the fourth lumbar vertebrae were removed, and the density of the vertebral bodies was determined. They were then subjected to compression testing. We found that all three estrogen/progestin regimens maintain bone density and all mechanical properties at a level indistinguishable from the control. However, the cyclic and continuous NET treatment results were, with the exception of density, also indistinguishable from those of the ovariectomized group. The estrogen plus interrupted NET group on the other hand, has a significantly greater compressive modulus and density than the ovariectomized group. In conclusion, with respect to the ovariectomized group, the estrogen plus interrupted NET treatment resulted in a superior density and compressive modulus. The remaining mechanical properties were equivalent to those resulting from the continuous or cyclic progestin regimens.

Notes: Summary The crystallinity of bone mineral at different stages of maturation has been measured by quantitative X-ray diffraction methods. Crystallinity measurements were made on tibial middiaphyses from 17-day embryonic chicks, newlyformed periosteal bone from embryonic chicks, and density-fractionated bone from post-hatch chickens from 5 weeks to 2 years of age. For a given animal age and degree of mineralization, crystallinity increases with animal age, indicating that changes in bone mineral occur even after mineralization is complete or nearly complete.

Notes: Abstract. The goal of this study was to evaluate the effects of chronically-elevated male levels of the potent androgen testosterone on the quality and quantity of both cancellous and cortical bone in a young (mean age 8.0 years), nonhuman female primate model (M. fascicularis). Thirteen intact female monkeys received continuous testosterone supplementation via subcutaneous implants over a 24-month period. A group of 16 untreated, intact, age-matched female monkeys served as controls. At sacrifice, the lumbar vertebrae and femora were recovered in order to analyze the bone mineral quality and quantity of cancellous and cortical bone, respectively, and compared to the control group. Mineralization profiles of the vertebrae and femora were obtained using the density fractionation technique. Chemical analysis of the three largest fractions retrieved by density fractionation was performed to evaluate differences in %Ca, %P, Ca/P ratio, and mineral content (%Ca + %PO4) between the control and experimental groups. In addition, unfractionated bone powder was examined by X-ray diffraction to identify any changes in crystal size. Coronal sections of vertebrae were analyzed for structural parameters using histomorphometry and image analysis. Cross sections taken at the midshaft diaphyseal femora were analyzed for structural macroscopic and intracortical parameters. A nonsignificant shift in the mineralization profile of the vertebrae was observed whereas there was a significant shift in the mineralization profile towards more dense bone in the treated femora as compared with controls (P 〈 0.05). There was no difference in terms of size/strain of the cortical or cancellous bone crystal as detected by X-ray diffraction. There was a trend towards an increase in cancellous bone area (B.Ar.) in the testosterone-treated vertebrae (P= 0.08) as compared with controls. The architecture of the cancellous bone remained nonsignificantly different between the treatment and control groups as evaluated by image analysis. There was a decrease in osteoid perimeter (P= 0.05) in the experimental group as compared with controls. There was a significant decrease in eroded perimeter measurements in the experimental group as compared with controls (P 〈 0.03). Although there was a trend towards an increase in cancellous bone area, mineralization was not significantly different in the vertebrae of testosterone-treated female monkeys, indicating that the newly-formed bone tissue became relatively normally mineralized over the two-year period. An increase in bone area, with indices of an overall decreased remodelling pattern as compared with controls, suggests that cancellous bone in the young, nonhuman female primate had been receptive to supraphysiologic levels of testosterone supplementation over the two-year period. There was a trend for an increase in cortical bone area and width with an increased periosteal perimeter in the testosterone-treated group as compare with controls. There was an increase in intracortical remodelling activity with a significant increase in percent porosity (P 〈 0.05), osteonal bone (P 〈 0.05), and mean wall width (P 〈 0.05) in the testosterone-treated group. In conclusion, the cancellous bone from female monkeys appeared to respond to the antiresorptive stimulus of male levels of testosterone with significantly diminished turnover parameters in this compartment. In contrast, the cortical bone compartment responded by displaying significant intracortical remodelling over a two-year period.