ALBERT

Notes: Abstract The goal of this study was to find out if bone can recover after long-term administration of bisphosphonate. Disodium pamidronate (APD) was given orally by gavage to mature beagle dogs at doses of 0, 2.5, 12.5, and 25 mg/kg/day for 1 year (0.1% concentration) and the animals were allowed to recover for another year. At sacrifice, the os ilium was used to determine bone mineralization profile and, subsequently, each density fraction was analyzed chemically. The ribs were used to determine the lattice parameters and the size of the apatite crystals of bone. The sternum was used to determine selected morphometric parameters using image analysis of specimen X-ray films and, subsequently, to determine bone mechanical properties using a 3-point bending technique. We found that the 12.5 and 25 mg/kg/day doses exhibit a significant shift towards greater mineralization versus control, whereas the lower dose (2.5 mg/kg/day) was indistinguishable from the controls. The lattice parameters and crystal size of bone apatite remained unchanged. The image analysis shows a dose-related increase in trabecular volume and thickness. The connectivity increased with dose but the anisotropy of bone remained unchanged. Both the elastic modulus and the maximum stress of bone remain unaffected by APD. We conclude that when dogs are treated with APD for 1 year, their bones can reestablish their physical-chemical characteristics (mineralization profile, chemistry, and crystal size/strain) after 1 year of recovery, provided that the treatment doss is 2.5 mg/kg/day. In addition, the mechanical properties of the bone remained unaffected and the gains in trabecular volume and thickness are maintained.

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.