Effect of Raloxifene Treatment on Osteocyte Apoptosis in Postmenopausal Women |
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Authors: | Huib W van Essen Paulien J Holzmann Marinus A Blankenstein Paul Lips Nathalie Bravenboer |
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Affiliation: | (1) Department of Endocrinology, VU University Medical Center, 1007 MB Amsterdam, The Netherlands;(2) Department of Clinical Chemistry, VU University Medical Center, 1007 MB Amsterdam, The Netherlands |
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Abstract: | Increased osteocyte apoptosis, as the result of estrogen deficiency, could play a role in the decrease of bone mass and bone
strength seen in postmenopausal osteoporosis. We investigated whether treatment with raloxifene of postmenopausal women with
osteoporosis affects osteocyte apoptosis. Transiliac bone biopsies were obtained from 26 osteoporotic women at baseline and
after 2 years of treatment with placebo or raloxifene. Immunohistochemical detection of cleaved caspase-3 was performed on
sections from nondecalcified bone biopsies to visualize apoptosis. In the trabecular bone total osteocytes, positively stained
osteocytes and empty lacunae were counted and percent positive cells and percent empty lacunae determined. Statistical evaluation
was performed by Wilcoxon’s paired t-test and Spearman’s rank correlations. There was no significant difference in percentage
positive osteocytes between baseline and follow-up biopsies in both the placebo and the raloxifene groups. The percentage
empty lacunae increased significantly in the placebo group (11.20 ± 1.43 vs. 9.00 ± 2.25, P = 0.014) but not in the raloxifene group. At baseline in both groups combined, there was a negative correlation between indices
of bone remodeling and the percentage positive osteocytes (bone formation rate/bone volume r = −0.67, P = 0.001). We found no direct evidence for an effect of raloxifene treatment on osteocyte apoptosis, but small effects of
raloxifene treatment cannot be excluded. The percent of apoptotic osteocytes was dependent on the level of bone remodeling
in an individual. |
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Keywords: | Apoptosis Histomorphometry Osteocyte Postmenopausal osteoporosis Raloxifene |
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