Repeated in vivo determinations of bone mineral density during parathyroidhormone treatment in ovariectomized mice

The recent development of different genetically modified mice with potentia lly interesting bone phenotypes has increased the demand for effective non- invasive methods to evaluate effects on bone of mice during growth and deve lopment, and for drug evaluation. In the present study, the skeleton was an alyzed by repeated in vivo scans using dual energy X-ray absorptiometry (DX A) and peripheral quantitative computed tomography (pQCT). Ovariectomized ( ovx) mice treated with parathyroid hormone (PTH) were used as an animal mod el to evaluate these two techniques at different times after the onset of t reatment. Female mice (6 weeks of age) were allocated randomly to four grou ps: (1) sham-operated+ vehicle; (2) ovx + vehicle; (3) sham-operated + PTH( 1-84) 150 mug/ kg per day; (4) ovx+PTH. Six weeks after ovariectomy the dru g treatment began and was continued for 8 weeks. The total body bone minera l content (BMC) and total body areal bone mineral density (BMD) were measur ed by DX-A. Ovariectomy reduced total body BMC and total body areal BMD by 6.2 +/- 1.7% and 2.6 +/- 0.9% respectively. No effect of PTH on total body BMC was seen during the treatment period. The trabecular volumetric BMD was measured by pQCT. Ovariectomy reduced the trabecular volumetric BMD by 52 +/- 6.7%. The pQCT technique detected a clear effect on trabecular volumetr ic BMD after 2 weeks of PTH treatment (ovx 94 +/- 29% and sham-operated 46 +/- 10% more than vehicle-treated). The cortical bone was measured in a mid -diaphyseal pQCT scan of the tibia. Ovariectomy reduced the cortical BMC by 9 +/- 2%. PTH treatment for 8 weeks increased cortical BMC in ovx mice. In conclusion, the pQCT technique is more sensitive than the DXA technique in the detection of bone loss after ovariectomy and increased bone mass aft er PTH treatment in mice. Notably, the pQCT, but not the DXA, technique det ected a dramatic effect as early as after 2 weeks of PTH treatment. Dynamic pQCT measurements will be useful for monitoring skeletal changes during gr owth and development, and for drug evaluation in mice.