DIRECT STEREOLOGICAL ESTIMATION OF 3-DIMENSIONAL CONNECTIVITY IN RAT VERTEBRAE - EFFECT OF ESTROGEN, ETIDRONATE AND RISEDRONATE FOLLOWING OVARIECTOMY

Newly developed unbiased stereological methods were employed to invest igate the effects of estrogen deficiency on the three-dimensional conn ectivity of vertebral cancellous bone from ovariectomized (OVX) rats, The effects of two classes of antiresorptive agents, estrogen and bisp hosphonates, on changes in connectivity in this animal model were also evaluated, Female rats were either sham-operated (sham-op) or surgica lly OVX at 90 days of age, OVX rats were administered either vehicle, estrogen (10 mu g/kg 17-beta estradiol, 5 days/week subcutaneously [SC ], etidronate disodium (5 mg/kg SC) or risedronate (5 mu g/kg SC), The bisphosphonates were administered daily for 1 week followed by 3 week s with no treatment, Treatment duration was 360 days, Systematic rando m sections, 30-mu m thick, were prepared from methylmethacrylate-embed ded decalcified second lumbar vertebrae, Total trabecular number and c onnectivity density were estimated using the ConnEulor principle, Vert ebral cancellous bone volume was estimated on undecalcified sections f rom the first lumbar vertebrae, Connectivity density and cancellous bo ne volume were significantly reduced (approximately 25% and 40%, respe ctively) in the OVX group compared with the sham-op group, Estrogen tr eatment essentially maintained connectivity and cancellous bone volume at the level of the sham-op rats, Connectivity density and total trab ecular number were significantly increased in the etidronate- and rise dronate-treated rats compared with both the sham-op and OVX rats, Thes e data demonstrate that reduction in the three-dimensional connectivit y of vertebral cancellous bone is a long-term consequence of ovariecto my in the rat, This reduction in connectivity can be effectively preve nted by the administration of antiresorptive agents such as estrogen, etidronate and risedronate. The increase in connectivity in the bispho sphonate-treated groups compared with the sham-op group may be a refle ction of the combined effects of these agents on resorptive cell recru itment and function in the growing rat skeleton, These results suggest that these agents may be clinically useful in preventing resorption-d ependent perforation and loss of trabecular elements which may be an i mportant component of estrogen-deficiency-related bone loss in women.