SUBREGION ANALYSIS OF THE RAT FEMUR - A SENSITIVE INDICATOR OF CHANGES IN BONE-DENSITY FOLLOWING TREATMENT WITH THYROID-HORMONE OR BISPHOSPHONATES

Measurement of bone mineral density (BMD) by dual X-ray absorptiometry (DXA) is a precise and accurate way to assess changes in BMD due to a variety of causes. However, the degree of bone loss may vary dependin g on the skeletal site examined. We postulated that interventions that change bone density would have a different effect on an area rich in trabecular bone, such as the distal femur, than on other subregions of the femur. Male Sprague-Dawley rats (325-350 g) were treated with tri iodothyronine (T-3), a bisphosphonate (pamidronate), or placebo for 21 days and then sacrificed. Ex vivo BMD of the proximal, distal, mid an d total femur were measured by DXA. We found that mean BMD of hyperthy roid rats was significantly lower than controls at all femoral subregi ons. However, the difference in mean BMD between hyperthyroid and cont rol rats was greatest at the distal femur (8.6%). In rats treated with bisphosphonate, mean BMD was significantly higher than controls at th e proximal, distal, and total femur. The difference in mean BMD betwee n controls and rats treated with bisphosphonate was greatest at the di stal femur (31.8%). Furthermore, pamidronate (APD)-treated rats had lo wer mean mid-femur BMD than controls. We conclude that changes in BMD after treatment with bisphosphonate or T-3 are greatest at the distal femur subregion, and that treatment with bisphosphonate may cause a sl ight reduction in mid-femur BMD. Future studies examining changes in B MD in the rat femur after interventions that alter mineral metabolism should include subregion analysis.