Parenteral pamidronate prevents thyroid hormone-induced bone loss in rats.

Pamidronate (APD) is a bisphosphonate that prevents bone loss from a variety of causes. We studied the role of APD in preventing thyroid hormone-induced bone loss. A total of 32 rats were assigned to one of four treatment groups: (1) -APD/triiodothyronine (-T3), (2) -APD/+T3, (3) +APD/-T3, or (4) +APD/+T3. In the first of two studies, the rats received APD for the first week and T3 for the second week, and then their blood was analyzed for alkaline phosphatase and osteocalcin. Alkaline phosphatase and osteocalcin were significantly higher (p < 0.05) in hyperthyroid rats (-APD/+T3, 3.9 +/- 0.25 mukat/liter and 23 +/- 1.6 nM, respectively) than in control animals (2.53 +/- 0.28 mukat/liter and 18.3 +/- 1.4 nM, respectively). Hyperthyroid rats pretreated with APD (+APD/+T3) had levels of alkaline phosphatase and osteocalcin no different from controls. In a second study, rats were divided into the same four groups, except they received APD/placebo and T3/placebo concomitantly for 3 weeks. At the end of the study, bone mineral density (BMD) of the femur, spine, and whole body was measured by dual-energy x-ray absorptiometry, and the calcium content of the femora was measured directly. In hyperthyroid rats (-APD/+T3) BMD was significantly lower than in controls in the spine (0.201 +/- 0.004 versus 0.214 +/- 0.002 g/cm2, p < 0.05) and femur (0.204 +/- 0.003 versus 0.218 +/- 0.002, p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Bone density is normal in male rats treated with finasteride.

Bone is an androgen-dependent tissue. It is not known whether normal bony growth and mineralization in males is dependent on testosterone alone, or whether its metabolite, dihydrotestosterone (DHT), also is required. To answer this question, we examined the effect of finasteride, an inhibitor of DHT synthesis, on bone in rats. Three-month-old male rats were treated with placebo, finasteride, or orchidectomy. The bone mineral densities (BMD) of the spine and whole body were measured in vivo by dual x-ray absorptiometry at weeks 0 and 11, and the BMD of the femur and tibia were measured ex vivo at week 11. Histomorphometric analysis was performed on the proximal tibia at week 11. The increase in spine and whole body BMD in finasteride-treated rats did not differ from that in controls, whereas these values were significantly lower in orchidectomized rats. Similarly, the BMD of the femur and tibia and the cancellous bone volume of the proximal tibia in finasteride-treated rats did not differ from those in controls, whereas these values were significantly lower in orchidectomized rats. In summary, bone development and density were normal in rats treated with finasteride. We conclude that selective DHT deficiency is not deleterious to the male rat skeleton.

Differentiating between orchiectomized rats and controls using measurements of trabecular bone density: a comparison among DXA, histomorphometry, and peripheral quantitative computerized tomography.

In studies of rat bone metabolism, trabecular bone density should be measured. Three established methods of measuring trabecular bone include trabecular bone volume by histomorphometry (BV/TV%), trabecular bone density by peripheral quantitative computerized tomography (pQCT), and areal bone density of trabecular-rich regions by dual x-ray absorptiometry (DXA). We compared the ability of these three methods to discriminate between orchiectomized (orchidectomized) rats and controls. Sixteen male Sprague-Dawley rats (400-425 g) were orchiectomized, and 16 others were controls. In vivo spine bone mineral density (BMD) was measured at the beginning of the study and again after 11 weeks. Rats were sacrificed, and ex vivo BMDs of the right femur and tibia were measured by DXA, followed by trabecular bone density of the right proximal tibia by pQCT. BT/TV% of the left proximal tibia was measured by histomorphometry. Differences between groups were detected by all three methods, but both the magnitude of the difference between groups and the variance of the measurements was much greater for histomorphometry and pQCT than for DXA. Consequently, the statistical significance for the difference between groups was comparable for all three methods. Of the sites measured with DXA, the proximal tibia had the greatest statistical significance for the difference between groups. In summary, all three methods can demonstrate the effect of orchiectomy on trabecular bone. The large differences between groups seen by histomorphometry are also seen by pQCT but not by DXA. We conclude that trabecular bone density by pQCT may be a reasonable surrogate for measurements by histomorphometry.

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 depending 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 triiodothyronine (T3), a bisphosphonate (pamidronate), or placebo for 21 days and then sacrificed. Ex vivo BMD of the proximal, distal, mid and total femur were measured by DXA. We found that mean BMD of hyperthyroid rats was significantly lower than controls at all femoral subregions. However, the difference in mean BMD between hyperthyroid and control rats was greatest at the distal femur (8.6%). In rats treated with bisphosphonate, mean BMD was significantly higher than controls at the proximal, distal, and total femur. The difference in mean BMD between controls and rats treated with bisphosphonate was greatest at the distal femur (31.8%). Furthermore, pamidronate (APD)-treated rats had lower mean mid-femur BMD than controls. We conclude that changes in BMD after treatment with bisphosphonate or T3 are greatest at the distal femur subregion, and that treatment with bisphosphonate may cause a slight reduction in mid-femur BMD. Future studies examining changes in BMD in the rat femur after interventions that alter mineral metabolism should include subregion analysis.