Direct stereological estimation of three-dimensional connectivity in rat vertebrae: effect of estrogen, etidronate and risedronate following ovariectomy.

Newly developed unbiased stereological methods were employed to investigate the effects of estrogen deficiency on the three-dimensional connectivity of vertebral cancellous bone from ovariectomized (OVX) rats. The effects of two classes of antiresorptive agents, estrogen and bisphosphonates, on changes in connectivity in this animal model were also evaluated. Female rats were either sham-operated (sham-op) or surgically OVX at 90 days of age. OVX rats were administered either vehicle, estrogen (10 micrograms/kg 17-beta estradiol, 5 days/week subcutaneously [SC], etidronate disodium (5 mg/kg SC) or risedronate (5 micrograms/kg SC). The bisphosphonates were administered daily for 1 week followed by 3 weeks with no treatment. Treatment duration was 360 days. Systematic random sections, 30-microns thick, were prepared from methylmethacrylate-embedded decalcified second lumbar vertebrae. Total trabecular number and connectivity density were estimated using the ConnEulor principle. Vertebral cancellous bone volume was estimated on undecalcified sections from the first lumbar vertebrae. Connectivity density and cancellous bone volume were significantly reduced (approximately 25% and 40%, respectively) in the OVX group compared with the sham-op group. Estrogen treatment essentially maintained connectivity and cancellous bone volume at the level of the sham-op rats. Connectivity density and total trabecular number were significantly increased in the etidronate- and risedronate-treated rats compared with both the sham-op and OVX rats. These data demonstrate that reduction in the three-dimensional connectivity of vertebral cancellous bone is a long-term consequence of ovariectomy in the rat. This reduction in connectivity can be effectively prevented by the administration of antiresorptive agents such as estrogen, etidronate and risedronate.(ABSTRACT TRUNCATED AT 250 WORDS)